Hopf bifurcation in an age-structured predator-prey system with Beddington-DeAngelis functional response and constant harvesting.

In this paper, an age-structured predator-prey system with Beddington-DeAngelis (B-D) type functional response, prey refuge and harvesting is investigated, where the predator fertility function f(a) and the maturation function ß ( a ) are assumed to be piecewise functions related to their maturation period τ . Firstly, we rewrite the original system as a non-densely defined abstract Cauchy problem and show the existence of solutions. In particular, we discuss the existence and uniqueness of a positive equilibrium of the system. Secondly, we consider the maturation period τ as a bifurcation parameter and show the existence of Hopf bifurcation at the positive equilibrium by applying the integrated semigroup theory and Hopf bifurcation theorem. Moreover, the direction of Hopf bifurcation and the stability of bifurcating periodic solutions are studied by applying the center manifold theorem and normal form theory. Finally, some numerical simulations are given to illustrate of the theoretical results and a brief discussion is presented.

Addition of nimotuzumab to concurrent chemoradiotherapy after induction chemotherapy improves outcomes of patients with locally advanced nasopharyngeal carcinoma.

Purpose: To investigate the survival outcomes and toxicities associated with the addition of nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Methods: Patients with stage III-IVA nasopharyngeal carcinoma who received IC and CCRT between January 2017 and October 2021 were retrospectively included. We aimed to compare the locoregional recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) between patients treated with CCRT+nimotuzumab and CCRT alone. Results: We included 411 patients in the analysis. Of these patients, 267 (65.0%) and 144 (35.0%) had CCRT+nimotuzumab and CCRT alone, respectively. Similar LRFS was found between those with and without nimotuzumab (92.9% vs. 92.6%, p = 0.855). The 3-year DMFS was 88.2% and 76.2% in those with and without nimotuzumab (p = 0.002). The 3-year DFS was 83.4% and 70.6% in those with and without nimotuzumab treatment (p = 0.003). The 3-year OS was 92.1% and 81.1% in those with and without nimotuzumab (p = 0.003). The multivariate Cox regression analysis indicated that the addition of nimotuzumab was independently associated with better DMFS (hazard ratio [HR] 0.606, p = 0.049), DFS (HR 0.613, p = 0.028), and OS (HR 0.497, p = 0.019). No significant differences in major toxicities were found between the two treatment arms, including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (all p > 0.05). Conclusion: The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in improving treatment outcomes and acceptable toxicities.

Disparities in Survival Outcomes Between Locally Advanced Cervical Squamous Cell Carcinoma and Adenocarcinoma Treated with Chemoradiotherapy.

Purpose: To determine the disparities in survival outcomes between stage IIB-IVA cervical squamous cell carcinoma (SCC) and adenocarcinoma (AC) treated with chemoradiotherapy. Methods: Patients diagnosed between 2004 and 2015 were retrospectively included from the Surveillance, Epidemiology, and End Results databases. Propensity score matching (PSM) was used in this study. The primary endpoints were cervical cancer-specific survival (CCSS) and overall survival (OS). Results: A total of 2752 patients were identified, including 87.5% (n=2408) were SCC and 12.5% (n=344) were AC. Patients with AC had inferior 5-year CCSS (67.5% vs 54.8%, P<0.001) and OS (58.4% vs 47.2%, P<0.001) compared to those with the SCC subtype. The hazard curve of cervical cancer-related death in AC peaked at 2 years (19%) and still small peaks in the 7 and 11 years of follow-up. Regarding SCC, cervical cancer-related deaths peaked at 2 years (15%) and the hazard rate was 2.0% during the six years of follow-up. The multivariate Cox regression analyses indicated that histology was an independent prognostic factor associated with survival outcomes. Patients with AC had significantly poor CCSS (P<0.001) and OS (P<0.001). Similar results were found after PSM. Conclusion: Our study demonstrates a significantly better prognosis for cervical SCC patients compared to those with cervical AC undergoing chemoradiotherapy. These results highlight the importance of histological subtyping in predicting treatment outcomes and tailoring therapeutic strategies.

A new species of Paraputo Laing (Hemiptera: Coccomorpha: Pseudococcidae) on Fagaceae from southern China.

A new species of mealybug (Hemiptera: Coccomorpha: Pseudococcidae), Paraputo nanlingensis Li & Wu, sp. n., is recorded on Fagaceae from Guangdong Province, China. The adult female is described and illustrated, and an identification key is provided to separate the adult females of Paraputo species known from China.

Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer.

Purpose: To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC). Methods: We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed. Results: A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved. Conclusion: The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.

Trends in survival of ovarian clear cell carcinoma patients from 2000 to 2015.

Purpose: To analyze changes in survival outcomes in patients with ovarian clear cell carcinoma (OCCC) treated consecutively over a 16-year period using a population-based cohort. Methods: We conducted a retrospective analysis of OCCC from 2000 to 2015 using data from the Surveillance, Epidemiology, and End Results (SEER) program. The ovarian cancer-specific survival (OCSS) and overall survival (OS) were analyzed according to the year of diagnosis. Joinpoint Regression Program, Kaplan-Meier analysis, and multivariate Cox regression analyses were used for statistical analysis. Results: We included 4257 patients in the analysis. The analysis of annual percentage change in OCSS (P=0.014) and OS (P=0.006) showed that patients diagnosed in later years had significantly better outcomes compared to those diagnosed in early years. The results of the multivariate Cox regression analyses showed that the year of diagnosis was the independent prognostic factor associated with OCSS (P=0.004) and had a borderline effect on OS (P=0.060). Regarding the SEER staging, the OCSS (P=0.017) and OS (P=0.004) of patients with distant stage showed a significant trend toward increased, while no significant trends were found in the survival of patients with localized or regional stage diseases. Similar trends were found in those aged <65 years or those treated with surgery and chemotherapy. However, no statistically significant changes in the survival rate were found in those aged ≥65 years or those receiving surgery alone regardless of SEER stage during the study period. Conclusions: Our study observed a significant increase in the survival outcomes in OCCC from 2000 to 2015, and patients aged <65 years and those with distant stage experienced a greater improvement in survival.

21-gene recurrence score in predicting the outcome of postoperative radiotherapy in T1-2N1 luminal breast cancer after breast-conserving surgery.

BACKGROUND: In those with one to three positive lymph nodes (N1) breast cancer (BC), the 21-gene recurrence score (RS) classification can be referred for decision-making on adjuvant chemotherapy. This study aimed to investigate the effect of RS in predicting the survival benefit of postoperative radiotherapy (PORT) in T1-2N1 BC with estrogen receptor-positive and human epidermal growth factor receptor 2-negative disease after breast-conserving surgery (BCS). METHODS: We included patients with BC and available RS data from the Surveillance, Epidemiology, and End Results Oncotype DX database. The chi-square test, Kaplan-Meier method, propensity score matching (PSM) as well as multivariable Cox proportional hazard analyses were used for statistical analyses. RESULTS: We included 6509 patients in the analysis. Of these patients, 5302 (85.5%) were treated with BCS + PORT, and 207 (15.5%) had BCS alone. There were 1419 (21.8%), 4319 (66.4%), and 771 (11.8%) patients being low-, intermediate-, and high-risk RS, respectively. After PSM, PORT was significantly associated with a 5-year overall survival (OS) advantage (95.1% vs. 90.5%, P < 0.001) compared to those without PORT, which similar breast cancer-specific survival (BCSS) was found between the treatment arms (P = 0.126). The sensitivity analyses showed that PORT was not associated with a better BCSS (P = 0.472) and OS (P = 0.650) than those without PORT in the low-risk RS cohort. However, PORT was associated with a better BCSS (P = 0.031) and OS (P < 0.001) compared to those without PORT in the intermediate/high-risk RS cohorts. CONCLUSIONS: Our study highlights the possible role of the RS in predicting the outcome of PORT in T1-2N1 luminal BC patients undergoing BCS.

A chromosome-level genome assembly of the forestry pest Coronaproctus castanopsis.

As an important forestry pest, Coronaproctus castanopsis (Monophlebidae) has caused serious damage to the globally valuable Gutianshan ecosystem, China. In this study, we assembled the first chromosome-level genome of the female specimen of C. castanopsis by merging BGI reads, HiFi long reads and Hi-C data. The assembled genome size is 700.81 Mb, with a scaffold N50 size of 273.84 Mb and a contig N50 size of 12.37 Mb. Hi-C scaffolding assigned 98.32% (689.03 Mb) of C. Castanopsis genome to three chromosomes. The BUSCO analysis (n = 1,367) showed a completeness of 91.2%, comprising 89.2% of single-copy BUSCOs and 2.0% of multicopy BUSCOs. The mapping ratio of BGI, second-generation RNA, third-generation RNA and HiFi reads are 97.84%, 96.15%, 97.96%, and 99.33%, respectively. We also identified 64.97% (455.3 Mb) repetitive elements, 1,373 non-coding RNAs and 10,542 protein-coding genes. This study assembled a high-quality genome of C. castanopsis, which accumulated valuable molecular data for scale insects.

Metronomic S1 Adjuvant Chemotherapy Improves Survival in Patients with Locoregionally Advanced Nasopharyngeal Carcinoma.

Purpose: To investigate the efficacy and safety of using metronomic S1 adjuvant chemotherapy in locoregionally advanced nasopharyngeal carcinoma (LANPC). Materials and Methods: We retrospectively collected data on patients diagnosed with LANPC between January 2016 and December 2021. All patients were treated with induction chemotherapy and concurrent chemoradiotherapy with or without metronomic chemotherapy (MC). Toxicities during MC were recorded. The chi-square test, Kaplan-Meier methods, propensity score matching (PSM), and Cox proportional hazards model were used for statistical analyses. Results: A total of 474 patients were identified, including 64 (13.5%) and 410 (83.5%) patients with or without receiving MC, respectively. Patients who received metronomic S1 had significantly better 3-year locoregional recurrence-free survival (LRFS) (100% vs. 90.9%, p=0.038), distant metastasis-free survival (DMFS) (98.5% vs. 84.1%, p=0.002), disease-free survival (DFS) (98.4% vs. 77.5%, p<0.001), and overall survival (OS) (98.0% vs. 87.7%, p=0.008) compared to those without metronomic S1. The multivariate prognostic analysis revealed that metronomic S1 was identified as an independent prognostic factor associated with better DMFS (hazard ratio [HR] 0.074, p=0.010), DFS (HR 0.103, p=0.002) and OS (HR 0.127, P=0.042), but not in LRFS (p=0.071). Similar results were found using PSM. Common adverse events observed in the metronomic S1 group included leukopenia, neutropenia, increased total bilirubin, anorexia, rash/desquamation, and hyperpigmentation. All patients with adverse events were grade 1-2. Conclusion: It is worth conducting a randomized controlled trial to assess the effect of metronomic S1 on survival outcomes and toxicities of LANPC.

Utilization and outcomes of the 21-gene recurrence score in de novo metastatic breast cancer.

BACKGROUND: Limited data exist regarding the utility and validity of the 21-gene recurrence score (RS) in patients with de novo metastatic breast cancer (dnMBC). This study aimed to investigate the practice patterns as well as associated survival outcomes based on 21-gene RS in dnMBC. RESEARCH DESIGN AND METHODS: The Surveillance, Epidemiology, and End Results Oncotype database was queried for women with hormone receptor-positive and Her2-negative dnMBC. RESULTS: A total of 153 patients were identified, including 62.7% and 37.3% of patients who had RS < 26 and ≥ 26, respectively. Patients with RS ≥ 26 were more likely to receive chemotherapy compared to those with RS < 26 (61.4% vs. 28.1%, p < 0.001). Patients with RS ≥ 26 had an inferior breast cancer-specific survival (BCSS) (2-year BCSS: 84.3% vs. 89.5, p = 0.067) and overall survival (OS) compared to those with RS < 26 (2-year OS: 76.9% vs. 87.4%, p = 0.018). The multivariate Cox proportional hazard models showed that those with RS ≥ 26 had a significantly inferior BCSS (hazard ratio [HR] 2.251, 95% confidence interval [CI] 1.056-4.799, p = 0.036) and OS (HR 2.151, 95%CI 1.123-4.120, p = 0.021) compared to those with RS < 26. CONCLUSIONS: The 21-gene RS assay is an important prognostic factor in patients with dnMBC.

Local treatment strategies in Stage IVB cervical squamous cell carcinoma and adenocarcinoma.

OBJECTIVE: To evaluate the effect of different local treatment strategies on survival outcomes in patients with Stage IVB cervical squamous cell carcinoma (SCC) and adenocarcinoma. METHODS: Patients diagnosed with Stage IVB cervical SCC and adenocarcinoma between 2004 and 2015 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Subgroup analysis was performed in those diagnosed between 2010 and 2015 and available for the sites of distant metastases. RESULTS: In total, 706 patients were identified in this study, including 378 (53.5%) and 328 (46.5%) diagnosed in 2004-2009 and 2010-2015, respectively. There were 525 (74.4%) and 181 (25.6%) patients with SCC and adenocarcinoma, respectively. Moreover, 274 (38.8%) and 432 (61.2%) patients received hysterectomy and primary radiotherapy, respectively. The results of the multivariate Cox regression analysis showed that histology and local treatment strategies were not related to cause-specific survival (CSS) and overall survival. In the SCC patients, patients who received primary radiotherapy had similar CSS (P = 0.312) and overall survival (P = 0.390) compared with those treated with surgery. In the adenocarcinoma patients, those who received primary radiotherapy had inferior CSS (P = 0.003) and overall survival (P < 0.001) compared with those treated with surgery. Similar results were found in those diagnosed 2004-2015 and 2010-2015 after propensity score matching. CONCLUSIONS: For patients with Stage IVB cervical cancer who received local therapy, surgery, and primary radiotherapy had similar survival in cervical SCC, whereas surgery had better survival outcomes compared with primary radiotherapy in those with cervical adenocarcinoma.

Nomogram Update to Predict the High Genomic Risk Breast Cancer by Different Races.

PURPOSE: To develop a nomogram to predict the high-risk recurrence score (RS) and to customize the nomogram for different races in early-stage hormone receptor (HoR)-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer. METHODS: Patients diagnosed between 2010 and 2015 were included from the surveillance, epidemiology, and end results oncotype DX database. The nomogram was assessed with a receiver operating characteristic curve to measure the area under the curve (AUC) with a 95% confidence interval (95% CI). The nomogram was developed and internally validated for discrimination and calibration, and then validated in different races. RESULTS: A total of 48,464 patients were included and randomly assigned to the training cohort (n = 36370, 75.0%) and validation cohort (n = 12,094, 25.0%). Patients in the training cohort were identified to develop the nomogram, including 32,683 (89.9%) White women, 3135 (8.6%) Black women, and 552 (1.5%) Chinese women. Five independent predictive factors for high-risk RS were included to develop the nomogram, including tumor grade, progesterone receptor status, histological subtype, race, and tumor stage. The AUC was 0.696 (95% CI, 0.682-0.710) in the training cohort and 0.700 (95% CI, 0.676-0.724) in the validation cohort. There was no significant difference between the training cohort and the validation cohort. When validating the nomogram classified by race, the AUC was 0.694 (95% CI, 0.682-0.706) for the White cohort, 0.708 (95% CI, 0.673-0.743) for the Black cohort, and 0.653 (95% CI, 0.565-0.741) for the Chinese cohort. CONCLUSION: The developed nomogram for predicting high-risk RS is available for different races in patients with HoR+/HER2- breast cancer, which could be used as qualified surrogates before ordering the 21-gene RS testing.

Development and performance of SIAT bPET: a high-resolution and high-sensitivity MR-compatible brain PET scanner using dual-ended readout detectors.

PURPOSE: Positron emission tomography/magnetic resonance imaging (PET/MRI) is a powerful tool for brain imaging, but the spatial resolution of the PET scanners currently used for brain imaging can be further improved to enhance the quantitative accuracy of brain PET imaging. The purpose of this study is to develop an MR-compatible brain PET scanner that can simultaneously achieve a uniform high spatial resolution and high sensitivity by using dual-ended readout depth encoding detectors. METHODS: The MR-compatible brain PET scanner, named SIAT bPET, consists of 224 dual-ended readout detectors. Each detector contains a 26 × 26 lutetium yttrium oxyorthosilicate (LYSO) crystal array of 1.4 × 1.4 × 20 mm3 crystal size read out by two 10 × 10 silicon photomultiplier (SiPM) arrays from both ends. The scanner has a detector ring diameter of 376.8 mm and an axial field of view (FOV) of 329 mm. The performance of the scanner including spatial resolution, sensitivity, count rate, scatter fraction, and image quality was measured. Imaging studies of phantoms and the brain of a volunteer were performed. The mutual interferences of the PET insert and the uMR790 3 T MRI scanner were measured, and simultaneous PET/MRI imaging of the brain of a volunteer was performed. RESULTS: A spatial resolution of better than 1.5 mm with an average of 1.2 mm within the whole FOV was obtained. A sensitivity of 11.0% was achieved at the center FOV for an energy window of 350-750 keV. Except for the dedicated RF coil, which caused a ~ 30% reduction of the sensitivity of the PET scanner, the MRI sequences running had a negligible effect on the performance of the PET scanner. The reduction of the SNR and homogeneity of the MRI images was less than 2% as the PET scanner was inserted to the MRI scanner and powered-on. High quality PET and MRI images of a human brain were obtained from simultaneous PET/MRI scans. CONCLUSION: The SIAT bPET scanner achieved a spatial resolution and sensitivity better than all MR-compatible brain PET scanners developed up to date. It can be used either as a standalone brain PET scanner or a PET insert placed inside a commercial whole-body MRI scanner to perform simultaneous PET/MRI imaging.

A novel model to predict the risk of hematological toxicity in lung adenocarcinoma patients with pemetrexed plus platinum chemotherapy based on real-world data.

BACKGROUND: Pemetrexed plus platinum chemotherapy is the first-line treatment option for lung adenocarcinoma. However, hematological toxicity is major dose-limiting and even life-threatening. The ability to anticipate hematological toxicity is of great value for identifying potential chemotherapy beneficiaries with minimal toxicity and optimizing treatment. The study aimed to develop and validate a prediction model for hematologic toxicity based on real-world data. METHODS: Data from 1754 lung adenocarcinoma patients with pemetrexed plus platinum chemotherapy regimen as first-line therapy were used to establish and calibrate a risk model for hematological toxicity using multivariate and stepwise logistic regression analysis based on real-world data. The predictive performance of the model was tested in a validation cohort of 753 patients. An area under the curve (AUC) of the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis were used to assess the prediction model. RESULTS: 5 independent factors (platinum, pre-use vitamin B12, cycle of chemotherapy before hematological toxicity, Hb before first chemotherapy, and PLT before first chemotherapy) identified from multivariate and stepwise logistic regression analysis were included in the prediction model. The hematological toxicity prediction model achieved a sensitivity of 0.840 and a specificity of 0.822. The model showed good discrimination in both cohorts (an AUC of 0.904 and 0.902 for the derivation and validation cohort ROC) at the cut-off value of 0.591. The calibration curve showed good agreement between the actual observations and the predicted results. CONCLUSION: We developed a prediction model for hematologic toxicity with good discrimination and calibration capability in lung adenocarcinoma patients receiving a pemetrexed plus platinum chemotherapy regimen based on real-world data.

Residual plasma Epstein-Barr virus DNA after intensity-modulated radiation therapy is associated with poor outcomes in nasopharyngeal carcinoma.

Aim: To investigate the effects of residual plasma Epstein-Barr virus (EBV) DNA levels after 3 months of intensity-modulated radiation therapy (IMRT) (postIMRT-EBV DNA) on prognosis in patients with nasopharyngeal carcinoma. Methods: Data from 300 patients were retrospectively collected for analysis. Results: Of these patients, 25 (8.3%) and 275 (91.7%) had positive and negative postIMRT-EBV DNA, respectively. Multivariate survival analysis showed that EBV DNA >688 IU/ml was independently associated with inferior distant metastasis-free survival (p = 0.003) and progression-free survival (p = 0.002). Moreover, postIMRT-EBV DNA was independently associated with inferior locoregional recurrence-free survival (hazard ratio: 4.325; p = 0.018), distant metastasis-free survival (hazard ratio: 10.226; p < 0.001) and progression-free survival (hazard ratio: 10.520; p < 0.001). Conclusion: Positive postIMRT-EBV DNA is a prognostic biomarker for nasopharyngeal carcinoma.

Steroid receptor coactivator-2 drives epithelial reprogramming that enables murine embryo implantation.

Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2's role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2d/d ) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2d/d luminal epithelium, respectively. These findings indicate that the SRC-2d/d luminal epithelium fails to exhibit a plasma membrane transformation (PMT) state known to be required for the development of uterine receptivity. Transcriptomics demonstrated that the expression of genes involved in steroid hormone control of uterine receptivity were significantly disrupted in the SRC-2d/d endometrium as well as genes that control epithelial tight junctional biology and the emergence of the epithelial mesenchymal transition state, with the latter sharing similar biological properties with PMT. Collectively, these findings uncover a new role for endometrial SRC-2 in the induction of the luminal epithelial PMT state, which is a prerequisite for the development of uterine receptivity and early pregnancy establishment.

Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives.

Breast cancer is the most commonly diagnosed cancer and the leading cause of death among female patients, which seriously threatens the health of women in the whole world. The treatments of breast cancer require the cooperation of a multidisciplinary setting and taking tumor load and molecular makers into account. For early breast cancer, breast-conserving surgery with radiotherapy or mastectomy alone remains the standard management, and the administration of adjuvant systemic therapy is decided by the status of lymph nodes, hormone receptors, and human epidermal growth factor receptor-2. For metastatic breast cancer, the goal of treatments is to prolong survival and maintain quality of life. This review will present the current advances and controversies of surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, gene therapy, and other innovative treatment strategies in early-stage and metastatic breast cancer.

The NR2F2-HAND2 signaling axis regulates progesterone actions in the uterus at early pregnancy.

Endometrial function is dependent on a tight crosstalk between the epithelial and stromal cells of the endometrium. This communication is critical to ensure a fertile uterus and relies on progesterone and estrogen signaling to prepare a receptive uterus for embryo implantation in early pregnancy. One of the key mediators of this crosstalk is the orphan nuclear receptor NR2F2, which regulates uterine epithelial receptivity and stromal cell differentiation. In order to determine the molecular mechanism regulated by NR2F2, RNAseq analysis was conducted on the uterus of PgrCre;Nr2f2f/f mice at Day 3.5 of pregnancy. This transcriptomic analysis demonstrated Nr2f2 ablation in Pgr-expressing cells leads to a reduction of Hand2 expression, increased levels of Hand2 downstream effectors Fgf1 and Fgf18, and a transcriptome manifesting suppressed progesterone signaling with an altered immune baseline. ChIPseq analysis conducted on the Day 3.5 pregnant mouse uterus for NR2F2 demonstrated the majority of NR2F2 occupies genomic regions that have H3K27ac and H3K4me1 histone modifications, including the loci of major uterine transcription regulators Hand2, Egr1, and Zbtb16. Furthermore, functional analysis of an NR2F2 occupying site that is conserved between human and mouse was capable to enhance endogenous HAND2 mRNA expression with the CRISPR activator in human endometrial stroma cells. These data establish the NR2F2 dependent regulation of Hand2 in the stroma and identify a cis-acting element for this action. In summary, our findings reveal a role of the NR2F2-HAND2 regulatory axis that determines the uterine transcriptomic pattern in preparation for the endometrial receptivity.

Xerostomia: An easily ignored symptom induced by induction chemotherapy in patients with nasopharyngeal carcinoma.

BACKGROUND: To investigate the prevalence and predictive factors of xerostomia during induction chemotherapy (IC) in patients with nasopharyngeal carcinoma (NPC). METHODS: We prospectively enrolled NPC patients who received IC between October 2020 and October 2021. The Visual Analogue Scale (VAS) and Xerostomia Inventory (XI) were used to evaluate the condition of xerostomia. The volume of the submandibular gland (SMG) was also calculated before and after IC. RESULTS: Fifty-two patients were enrolled in this study. Of these patients, 32.7% (n = 17) experienced xerostomia before IC. There were 32 (61.5%) patients suffered from xerostomia after IC, including 21 (40.4%) patients with newly diagnosed xerostomia after IC and 11 (21.1%) patients complained their xerostomia aggravated in those with xerostomia before IC. The median XI scores increased from 11 (standard deviation [SD], 2.930) to 18 (SD 3.995), 16 (SD 3.605), and 17 (SD 4.331) after the first, second, and third cycles of IC, respectively. The median score of VAS also increased from 0 to 4 during the following three cycles of IC. In those with IC-related xerostomia, the SMG volume after IC was significantly decreased compared with those without IC-related xerostomia (P = 0.001). The reduction of the SMG volume after IC was the independent risk factor for xerostomia (P = 0.002). CONCLUSION: Approximately two-thirds of NPC patients suffered from IC-related xerostomia and patients with a reduction of SMG volume after IC had a higher risk of xerostomia.