Stress Dissipation Driven by Multi-Interface Built-In Electric Fields and Desert-Rose-Like Structure for Ultrafast and Superior Long-Term Sodium Ion Storage.

The kinetics and durability of conversion-based anodes greatly depend on the intrinsic stress regulating ability of the electrode materials, which has been significantly neglected. Herein, a stress dissipation strategy driven by multi-interface built-in electric fields (BEFs) and architected structure, is innovatively proposed to design ultrafast and long-term sodium ion storage anodes. Binary Mo/Fe sulfide heterostructured nanorods with multi-interface BEFs and staggered cantilever configuration are fabricated to prove our concept. Multi-physics simulations and experimental results confirm that the inner stress in multiple directions can be dissipated by the multi-interface BEFs at the micro-scale, and by the staggered cantilever structure at the macro-scale, respectively. As a result, our designed heterostructured nanorods anode exhibits superb rate capability (332.8 mAh g-1 at 10.0 A g-1 ) and durable cyclic stability over 900 cycles at 5.0 A g-1 , outperforming other metal chalcogenides. This proposed stress dissipation strategy offers a new insight for developing stable structures for conversion-based anodes.

Association of the Kiwi OmniCup system with maternal and neonatal morbidity: A retrospective cohort study.

OBJECTIVE: To discuss the effect of the Kiwi OmniCup system on reducing adverse maternal and neonatal outcomes and provide a reference for assisted vaginal delivery methods. METHODS: Women who gave birth to singleton term neonates in a cephalic presentation and underwent assisted vaginal delivery from 2017 to 2021 were eligible for inclusion in the study; they were divided into a Kiwi OmniCup system group and a forceps group. Binary logistic regression analysis was used to observe and compare maternal and neonatal outcomes. The primary outcomes were severe maternal and neonatal morbidity. Severe maternal morbidity was defined as the occurrence of at least one of the following outcomes: third- or fourth-degree perineal lacerations, refractory postpartum hemorrhage, thrombotic events, amniotic fluid embolism, admission to the intensive care unit, and maternal death. Severe neonatal morbidity was defined as the occurrence of at least one of the following outcomes: neonatal asphyxia requiring resuscitation or intubation, neonatal head and face injuries, neonatal fracture, and admission to the neonatal intensive care unit for longer than 24 h. RESULTS: The rate of severe neonatal morbidity in the forceps group was significantly higher than that in the Kiwi OmniCup system group, the differences between the two groups were significant (27.2% vs. 42.3%, P < 0.001), and there was no significant difference in the rate of severe maternal morbidity between the two groups (30% vs. 30%, P > 0.05). Binary logistic regression analysis showed that Kiwi OmniCup system-assisted delivery reduced severe neonatal morbidity (adjusted odds ratio 0.49; 95% confidence interval 0.33-0.73) and did not increase severe maternal morbidity compared with forceps-assisted delivery. CONCLUSION: The Kiwi OmniCup system, which can reduce the incidence of severe neonatal morbidity without increasing the incidence of serious adverse maternal outcomes, is worthy of clinical promotion.

Single-cell metabolite profiling enables information-rich classification of lymphocyte types and subtypes.

Lymphocytes play crucial roles in the human immune system; however, detailed metabolite characteristics need to be further investigated. Herein, we propose a lymphocyte classification method based on metabolite profiling at the single-cell level. The percentages of different lymphocyte types were calculated with a low margin of error, confirming that the metabolites could serve as a basis for lymphocyte classification. Furthermore, we analyzed the CD4/CD8 ratio in human peripheral blood to verify the feasibility of this method for the classification of lymphocyte subtypes. The proposed method is expected to be a potential tool for the clinical diagnosis of lymphocyte-related diseases.

One pot preparation of muti-mode nanoplatform to combat ovarian cancer.

Ovarian cancer is one of the most common gynecological cancers with high mortality rate. The battle against ovarian cancer usually impaired by the evolved multidrug resistance (MDR) phenotype as well as metastasis in cancers, which urgently call for the development of multi-mode strategies to overcome the MDR and reduce metastasis. Considering the good benefits of ferroptosis and photothermal therapy (PTT) in cancer management, we herein proposed a facile way to construct nanoparticle platform (Fe-Dox/PVP) composed of ferric chloride, doxorubicin (Dox) and polyvinyl pyrrolidone (PVP) for the multi-mode therapy of ovarian cancer using chemotherapy, ferroptosis and mild hypothermia PTT. Our results demonstrated that Fe-Dox/PVP with mild hypothermia was shown to have improved endosomal escape/drug delivery, enhanced ferroptosis induction and good tumor targeting effects. Most importantly, the integration of all three effects into one platform provided increased anti-metastasis effect and promising in vitro/in vivo anticancer performance with high biocompatibility. In this study, we offer a facile and robust way to prepare a multi-mode nanoplatform to combat ovarian cancer, which can be further extended for the management of many other cancers.

Predicting isocitrate dehydrogenase genotype, histological phenotype, and Ki-67 expression level in diffuse gliomas with an advanced contrast analysis of magnetic resonance imaging sequences.

Background: The present study aimed to establish a robust predictive model based on a machine learning (ML) algorithm providing preoperative noninvasive diagnosis and to further explore the contribution of each magnetic resonance imaging (MRI) sequence to the classification to help select images for future model development. Methods: This was a retrospective cross-sectional study, and consecutive patients with histologically confirmed diffuse gliomas in our hospital from November 2015 to October 2019 were recruited. The participants were grouped into a training and testing set based on a ratio of 8:2. Five MRI sequences were employed to develop the support vector machine (SVM) classification model. An advanced contrast analysis of single-sequence-based classifiers was performed, according to which different sequence combinations were tested, and the best one was selected to form an ultimate classifier. Patients whose MRIs were acquired with other types of scanners formed an additional, independent validation set. Results: A total of 150 patients with gliomas were used in the present study. Contrast analysis revealed that the contribution of the apparent diffusion coefficient (ADC) was the most significant [accuracies were as follows: histological phenotype, 0.640; isocitrate dehydrogenase (IDH) status, 0.656; and Ki-67 expression, 0.699] and that of T1 weighted imaging was limited (accuracies were as follows: histological phenotype, 0.521; IDH status, 0.492; and Ki-67 expression, 0.556). The ultimate classifiers for IDH status, histological phenotype, and Ki-67 expression achieved promising performances with area under the curve (AUC) values of 0.88, 0.93, and 0.93, respectively. The classifiers for the histological phenotype, IDH status, and Ki-67 expression correctly predicted 3 of 5 subjects, 6 of 7 subjects, and 9 of 13 subjects in the additional validation set, respectively. Conclusions: The present study showed satisfactory performance in predicting the IDH genotype, histological phenotype, and Ki-67 expression level. The contrast analysis revealed the contribution of different MRI sequences and suggested that the combination of all the acquired sequences was not the optimal strategy to build the radiogenomics-based classifier.

Renal angiomyolipoma with tumor thrombi: Clinical analysis of 18 cases in a single-center experience.

PURPOSE: To improve understanding of the clinical features of renal angiomyolipoma (AML) accompanied by tumor thrombus (TT). METHODS: From January 2017 to February 2022, 18 patients with AML and TT were enrolled. We retrospectively analyzed them and there were 6 cases of epithelial AML (EAML) and 12 of classical AML (CAML). We compared the key variables between the two cohorts. RESULTS: The mean age of the 18 cases was 42.0 (standard deviation [SD] 13.4) years and 14 (77.8%) were female. Eleven (61.1%) tumors were on the right side. Only two (11.1%) cases presented with flank pain. The mean follow-up time was 33.6 (IQR: 20.1-48.5) months. All participants were alive at the end of follow-up. One case developed lung metastases 21 months after operation but entered remission after 2 years of everolimus treatment. The imaging diagnoses of all CAML cases were consistent with the pathology, while all imaged EAML cases were diagnosed with carcinomas. Five EAML cases, but only one CAML case, exhibited necrosis (83.3 vs. 8.3%, P = 0.001). The Ki-67 index of the EAML group was significantly higher than that of the CAML group (7 vs. 2, P = 0.004). CONCLUSIONS: Compared to CAML, EAML tended to be associated with a higher imaging misdiagnosis rate, and was more commonly associated with necrosis and a higher Ki-67 index. Surgery remains the prime treatment for nonmetastatic AML with TT; such cases have a relatively good prognosis despite the malignant potential.

Dual-Functional Z-Scheme TiO2 @MoS2 @NC Multi-Heterostructures for Photo-Driving Ultrafast Sodium Ion Storage.

Exploiting dual-functional photoelectrodes to harvest and store solar energy is a challenging but efficient way for achieving renewable energy utilization. Herein, multi-heterostructures consisting of N-doped carbon coated MoS2 nanosheets supported by tubular TiO2 with photoelectric conversion and electronic transfer interfaces are designed. When a photo sodium ion battery (photo-SIB) is assembled based on the heterostructures, its capacity increases to 399.3 mAh g-1 with a high photo-conversion efficiency of 0.71 % switching from dark to visible light at 2.0 A g-1 . Remarkably, the photo-SIB can be recharged by light only, with a striking capacity of 231.4 mAh g-1 . Experimental and theoretical results suggest that the proposed multi-heterostructures can enhance charge transfer kinetics, maintain structural stability, and facilitate the separation of photo-excited carriers. This work presents a new strategy to design dual-functional photoelectrodes for efficient use of solar energy.

DV-Hop Algorithm Based on Multi-Objective Salp Swarm Algorithm Optimization.

The localization of sensor nodes is an important problem in wireless sensor networks. The DV-Hop algorithm is a typical range-free algorithm, but the localization accuracy is not high. To further improve the localization accuracy, this paper designs a DV-Hop algorithm based on multi-objective salp swarm optimization. Firstly, hop counts in the DV-Hop algorithm are subdivided, and the average hop distance is corrected based on the minimum mean-square error criterion and weighting. Secondly, the traditional single-objective optimization model is transformed into a multi-objective optimization model. Then, in the third stage of DV-Hop, the improved multi-objective salp swarm algorithm is used to estimate the node coordinates. Finally, the proposed algorithm is compared with three improved DV-Hop algorithms in two topologies. Compared with DV-Hop, The localization errors of the proposed algorithm are reduced by 50.79% and 56.79% in the two topology environments with different communication radii. The localization errors of different node numbers are decreased by 38.27% and 56.79%. The maximum reductions in localization errors are 38.44% and 56.79% for different anchor node numbers. Based on different regions, the maximum reductions in localization errors are 56.75% and 56.79%. The simulation results show that the accuracy of the proposed algorithm is better than that of DV-Hop, GWO-DV-Hop, SSA-DV-Hop, and ISSA-DV-Hop algorithms.

Molecular Basis for the Selectivity of the Succinate Dehydrogenase Inhibitor Cyflumetofen between Pest and Predatory Mites.

Acaricides that act as inhibitors of the mitochondrial succinate dehydrogenase (SDHIs) provide excellent control of phytophagous mites but display limited toxicity to predatory mites and other beneficial organisms. However, the molecular mechanism of selectivity is not fully understood. Here, we first confirm that SDHI acaricides are over 10,000-fold more toxic to spider mites than predatory mites. Next, we show that differential penetration, pro-acaricide activation, or metabolism are most likely not the main reason for this selectivity. In contrast, the inhibition of AB-1 on the SDH target is approximately 200-fold more potent in spider mites compared to predatory mites, revealing strong target-site selectivity. Strikingly, a key motif associated with differential binding was identified and validated by gene editing in Drosophila. Our findings contribute to understanding the selectivity of SDHIs, which can be used for the rational design of selective acaricides in support of an integrated pest management.

18 F-DCFPyL positron emission tomography/magnetic resonance imaging-guided ultrasound fusion biopsy is an identical pathway in prostate cancer diagnosis.

BACKGROUND: Prostate biopsy is still unavoidable in patients with a rising prostate-specific antigen even though multiparametric magnetic resonance imaging (MRI) is widely used. 18 F-DCFPyL positron emission tomography (PET)/MRI was proved to be promising both in sensitivity and specificity. But its guiding fusion biopsy and the advantages in the diagnosis of prostate disease is seldom reported. This study aimed to verify the feasibility and advantage of 18 F-DCFPyL PET/MRI-guided fusion targeted biopsy (TB) over whole-mount histopathology (WMH) for prostate cancer diagnosis. METHODS: A prospective study of 94 biopsy-naïve patients were conducted using 18 F-DCFPyL PET/MRI scans and scored on a scale of 1-4. Systematic biopsy was performed for all patients. Patients with suspicious lesions also underwent PET/MRI/transrectal ultrasound-guided fusion biopsy. Patients with pathologically confirmed cancer underwent surgery and WMH sections. Systematic biopsy was compared with TB for the detection of index tumors (ITs). Significant cancer was defined as Grade group (GG) 2 or higher no matter the length of the cancer core. RESULTS: 18 F-DCFPyL PET/MRI detected 30/94 (32%) patients with a score of 4, all of whom were verified to have prostate cancer. While it detected 10 patients with a score of 1 (10.6%), they were shown to have no cancer. The sensitivity and specificity of 18 F-DCFPyL PET/MRI were 94.4% and 75%, respectively, if images with a score of 3 are defined as positive. Systematic biopsy detected 18% (203/1128) samples as prostate cancer; conversely, TB detected 113 samples out of 259 scores (43.6%). A statistically significant difference was seen between the PCa detection rates by TB and SB (p < 0.001). All targeted lesions were pathologically proven to be the IT on WMH. CONCLUSIONS: In biopsy-naïve patients, the ultrasound fusion biopsy targeted by 18 F-DCFPyL PET/MRI is an identical pathway for the detection of prostate cancer.

Subchorionic hematoma and risk of preterm delivery: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the association between early pregnancy with subchorionic hematoma and preterm delivery and other adverse pregnancy outcomes in singleton pregnancies. DATA SOURCES: English studies published from 2000 to July 15, 2022 were retrieved from PubMed, Web of Science, and the Cochrane Library. STUDY ELIGIBILITY CRITERIA: The inclusion criteria were: singleton pregnancy, subchorionic hematoma, and perinatal outcomes. Studies including multiple pregnancy, basic molecular studies, case reports (series), and conference reviews were excluded. METHODS: Data analysis was mainly conducted with Review Manager (RevMan) and Stata, and the results were represented with odds ratios and 95% confidence intervals. The methodological quality of the included studies was evaluated by the Cochrane risk assessment scale. RESULTS: In total, 370 studies were retrieved from the above databases. Our review included 16 studies and divided them into 2 subgroups: natural pregnancy (12 studies) and assisted reproductive pregnancy (4 studies). The relevant characteristics of each study were analyzed in detail. The primary outcome was preterm delivery. The secondary outcomes were miscarriage, fetal growth restriction, cesarean delivery, and preeclampsia. We found that subchorionic hematoma in the first trimester was not significantly associated with preterm delivery (odds ratio, 1.11; 95% confidence interval, 0.82-1.51) or other adverse outcomes in singleton pregnancy. Regression analysis found that the large heterogeneity of the included studies might be related to whether the included study population (early pregnancy with subchorionic hematoma) was complicated with threatened abortion (P<.05). However, no studies caused large heterogeneity according to sensitivity analysis. Finally, 15 studies related to preterm delivery did not have publication bias (Egger test: P=.26). However, subchorionic hematoma in the first trimester was associated with miscarriage in single pregnancies (natural pregnancy: odds ratio, 3.07; 95% confidence interval, 1.98-4.75; assisted reproductive pregnancy: odds ratio, 1.45; 95% confidence interval, 1.1-1.90). CONCLUSION: In singleton pregnancy, we found no association between subchorionic hematoma in the first trimester and preterm delivery. Although there was a correlation with miscarriage, the possible gestational age of miscarriage was not stated. More studies are needed to further address the herein posed research questions.

Cutaneous metastasis of carcinomatous component of ovarian carcinosarcoma: A case report and review of the literature.

Skin metastasis of ovarian cancer is extremely rare. We report an unusual case of ovarian carcinosarcoma with cutaneous metastasis of carcinomatous component that displayed distinct clinical manifestation. A 48-year-old woman presented to the dermatologist complaining of a new onset of erythematous, plaque-like skin rash with multiple small nodules on the left inner thigh, the area measuring 8 × 5cm. While the patient had no history of dermatologic conditions, she underwent a total hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and lymph node dissection 16 months ago with a pathology confirmed stage IIIC ovarian carcinosarcoma. Of note, the carcinomatous component, mainly adenocarcinoma with hybrid features of seromucinous, endometrioid and minor high-grade serous carcinoma, involved bilateral fallopian tubes, omentum, and parametrium with extensive lymph node metastases. A skin biopsy specimen revealed an adenocarcinoma involving epidermis, dermis, and subcutaneous tissue with nodular contours, consistent with metastatic carcinomatous component of carcinosarcoma. Both carcinomatous component of primary ovarian carcinosarcoma and metastatic adenocarcinoma in the skin demonstrated Pax8, WT-1, and ER positivity and a mutation pattern of p53. The patient passed away 15 months after identification of skin metastasis. This case represents a unique example of cutaneous metastasis of ovarian carcinosarcoma with distinct clinical manifestation and detailed histopathological description. Alertness to the possibility of cutaneous metastasis, in combination with clinical history, morphological and immunohistochemical findings, is critical for a definitive classification.

Research on Evaluation Method for Urban Water Circulation Health and Related Applications: A Case Study of Zhengzhou City, Henan Province.

The acceleration of urbanization and climate change has increasingly impacted the health level of urban dual water cycles. In order to accurately evaluate the health status of urban water cycles, the evaluation system covers four standard layers of water ecology, water abundance, water quality and water use, including 19 basic indicators such as water storage change and annual average precipitation. Three-scale AHP and EFAST algorithms are adopted to set the criterion and index layer weights. Water-cycle health assessment models are based on the improved TOPSIS model. The model evaluated Zhengzhou's water cycle health from 2011 to 2021. We compared the TOPSIS model and FCE method to ensure the scientific objectivity of the evaluation results. The evaluation results indicated that the water cycle in Zhengzhou City improved annually, and the relative progress in 2020 was 0.567 in a sub-health state. The eco-environmental water demand, green coverage rate of the built district, water resources amount, and industry's water consumption per unit of value added (CNY 10,000) were the major obstacles. These four factors have preponderantly influenced Zhengzhou City's water cycle health. Our research results provide scientific reference for Zhengzhou to achieve a healthy urban water cycle and regional sustainable development.

Correlation between apparent diffusion coefficient and tumor-stroma ratio in hybrid 18F-FDG PET/MRI: preliminary results of a rectal cancer cohort study.

Background: To explore possible correlations between the tumor-stroma ratio (TSR) and different imaging features of fluorine-18-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) in untreated rectal cancer patients. Methods: A patients with rectal cancer were included in this study. All participants were examined preoperatively with whole-body 18F-FDG PET/MRI. Two pathologists evaluated the TSR of tumors together. Apparent diffusion coefficient (ADC) values and PET-related parameters of the primary lesions were measured and compared between the stroma-high and stroma-low groups. Pearson's correlation or Spearman's rank correlation were used to evaluate the correlation between the ADC values, PET-related parameters, and pathological indices. Results: Our results showed that in the untreated rectal cancer patients, the ADC mean values correlated with the TSR (r=0.327; P=0.007), and stroma-high (low TSR) rectal cancer corresponded to relatively lower ADC mean values (813.54±88.68 vs. 879.92±133.18; P=0.018). The ADC mean and ADC minimum (ADCmin) values were found to be negatively correlated with the pathological T stages (r=-0.384, P=0.001; r=-0.416, P=0.001, respectively) as well as the largest tumor diameters (r=-0.340, P=0.005; r=-0.314, P=0.010, respectively) of rectal cancer. In addition, the pathological T stages correlated with all PET-related metabolic parameters, including mean standard uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) (r=0.338, P=0.006; r=0.350, P=0.004; r=0.326, P=0.007; and r=0.472, P<0.001, respectively). Our results also identified associations between the ADCmin values and SUVmean, SUVmax, and TLG (r=-0.335, P=0.006; r=-0.343, P=0.005; and r=-0.343, P=0.005, respectively). However, there were no statistical correlations between the PET/MRI parameters and the immunohistochemical (IHC) results. Conclusions: This study indicated that the intratumoral heterogeneity measured by PET/MRI may reflect characteristics of the tumor microenvironment. Hence, PET/MRI parameters might be helpful in predicting tumor aggressiveness and prognosis.

Nickel-catalyzed Thioester Transfer Reaction with sp2-Hybridized Electrophiles.

We report a thioacylation transfer reaction based on nickel-catalyzed C-C bond cleavage of thioesters with sp2-hybridized electrophiles. Aryl bromides, iodides, and alkenyl triflates can participate in thioester transfer reaction of aryl thioesters, affording a wide range of structurally diverse new thioesters in yields of up to 98% under mild reaction conditions. With this protocol, it is possible to construct alkenyl thioesters from the corresponding ketones through the generation of alkenyl triflates.

Highly selective single and multiple deuteration of unactivated C(sp3)-H bonds.

Selective deuteration of unactivated C(sp3)-H bonds is a highly attractive but challenging subject of research in pharmaceutical chemistry, material science and synthetic chemistry. Reported herein is a practical, highly selective and economical efficient hydrogen/deuterium (H/D) exchange of unactivated C(sp3)-H bonds by synergistic photocatalysis and hydrogen atom transfer (HAT) catalysis. With the easily prepared PMP-substituted amides as nitrogen-centered radical precursors, a wide range of structurally diverse amides can undergo predictable radical H/D exchange smoothly with inexpensive D2O as the sole deuterium source, giving rise to the distal tertiary, secondary and primary C(sp3)-H bonds selectively deuterated products in yields of up to 99% and excellent D-incorporations. In addition to precise monodeuteration, this strategy can also achieve multideuteration of the substrates contain more than one remote C(sp3)-H bond, which opens a method to address multi-functionalization of distal unactivated C(sp3)-H bonds.

Attention-modulated multi-branch convolutional neural networks for neonatal brain tissue segmentation.

Accurate measurement of brain structures is essential for the evaluation of neonatal brain growth and development. The conventional methods use manual segmentation to measure brain tissues, which is very time-consuming and inefficient. Recent deep learning achieves excellent performance in computer vision, but it is still unsatisfactory for segmenting magnetic resonance images of neonatal brains because they are immature with unique attributes. In this paper, we propose a novel attention-modulated multi-branch convolutional neural network for neonatal brain tissue segmentation. The proposed network is built on the encoder-decoder framework by introducing both multi-scale convolutions in the encoding path and multi-branch attention modules in the decoding path. Multi-scale convolutions with different kernels are used to extract rich semantic features across large receptive fields in the encoding path. Multi-branch attention modules are used to capture abundant contextual information in the decoding path for segmenting brain tissues by fusing both local features and their corresponding global dependencies. Spatial attention connections between the encoding and decoding paths are designed to increase feature propagation for both avoiding information loss during downsampling and accelerating model training convergence. The proposed network was implemented in comparison with baseline methods on three neonatal brain datasets. Our network achieves the average Dice similarity coefficients/the average Hausdorff distances of 0.9116/8.1289, 0.9367/9.8212 and 0.8931/8.1612 on the customized dCBP2021 dataset, 0.8786/11.7863, 0.8965/13.4296 and 0.8539/10.462 on the public NBAtlas dataset, as well as 0.9253/7.7968, 0.9448/9.5472 and 0.9132/7.5877 on the public dHCP2017 dataset in partitioning the brain into gray matter, white matter and cerebrospinal fluid, respectively. The experimental results show that the proposed method achieves competitive state-of-the-art performance in neonatal brain tissue segmentation. The code and pre-trained models are available at https://github.com/zhangyongqin/AMCNN.

Tumoral Morphologic Features From Cervical Biopsies That Are Predictive of a Negligible Risk for Nodal Metastasis and Tumor Recurrence in Usual-type Cervical Adenocarcinomas: A Multi-institutional Study.

The metastatic or recurrent potential of localized human papillomavirus-associated endocervical adenocarcinoma (HPVA EAC) is difficult to predict, especially based upon biopsy alone. Recent analyses of small cohorts indicate that high tumor nuclear grade (TNG) and the presence of necrotic tumor debris (NTD) from HPVA EACs in cervical biopsy specimens are highly predictive of nodal metastasis (NM). In the present study, we aimed to investigate how reliably tumoral morphologic features from cervical biopsy specimens predict NM or tumor recurrence (TR) and patient outcomes in a large cohort of endocervical adenocarcinoma patients. A cohort comprised of 397 patients with HPVA EAC treated at 18 institutions was identified, and cervical biopsies were paired with their associated complete tumor resections for a total of 794 specimens. A variety of tumoral histologic features were examined for each paired specimen, including TNG (assessed on a 3-tiered scale of increasing abnormalities-TNG1, TNG2, TNG3) and NTD (defined by the presence of necrotic and apoptotic tumor cells within tumor glandular lumens admixed with granular and eosinophilic amorphous material and inflammatory cells), which were correlated with outcomes. The distribution of TNG in biopsies was as follows: 86 (21.7%) TNG1, 223 (56.2%) TNG2, and 88 (22.2%) TNG3. NTD was identified in 176 (44%) of the biopsy specimens. The sensitivity, specificity, positive predictive value, and negative predictive value of a TNG1 assignment in the biopsy being predictive of the same assignment in the full resection were 0.82 (95% confidence interval [CI]: 0.7-0.9), 0.895 (0.86-0.93), 0.593 (0.48-0.696), and 0.96 (0.94-0.98), respectively. Respective values for an NTD-negative status were 0.89 (95% CI: 0.83-0.92), 0.715 (0.64-0.77), 0.72 (0.65-0.77), and 0.89 (0.83-0.93), respectively. Compared with the other cases in each category, both TNG1 and an NTD-negative status were each significantly associated with lower rates of NM (odds ratio for TNG1=0.245, 95% CI: 0.070-0.857, P=0.0277; for NTD=0.199, 95% CI: 0.094-0.421, P<0.0001) and TR (odds ratio for TNG1=0.225, 95% CI: 0.051-0.987, P=0.0479; for NTD=0.367, 95% CI: 0.171-0.786, P=0.0099) independent of depth of stromal invasion, lymphovascular invasion, tumor size, FIGO stage, and Silva pattern. Overall, 73/379 (19%) cases were both TNG1 and NTD-negative on the biopsy, and none of these 73 cases showed NM (0%), but a single case (1.4%) showed TR. In contrast, among the 324 biopsies with TNG2/3 and/or presence of NTD, 62 (19.1%) had NM, and 41 (12.9%) had TR. In summary, 2 variables in combination (ie, TNG1 and NTD-negative) identified a subset of HPVA EAC patients-∼19%-with a 0% frequency of nodal metastases and only 1.4% frequency of recurrence. Biopsies highly but imperfectly predicted these features. Nonetheless, these findings may potentially be of clinical utility in the risk stratification of patients with HPVA EACs. This may allow some patients with a minimal risk of nodal metastases and TR to be identified at the biopsy phase, thereby facilitating more personalized, possibly less aggressive treatment.

CUMS and dexamethasone induce depression-like phenotypes in mice by differentially altering gut microbiota and triggering macroglia activation.

BACKGROUND: Although the link between gut microbiota and depression has been suggested, changes of gut microbiota vary largely among individuals with depression. AIMS: Explore the heterogeneity of microbiota-gut-brain axis and new pathogenic characteristics in murine models of depression. METHODS: Adolescent female mice were randomly divided into control (CON) group (n=10), chronic unexpected mild stress (CUMS) group (n=15) and dexamethasone (DEX) group (n=15). Mice in the DEX group were gavaged twice a day with 0.2 mg/kg of DEX for 5 weeks, whereas CON mice were given the same amount of solvent. Mice in the CUMS group were exposed to stressors. After behavioural evaluations, all mice were sacrificed for harvesting tissues and blood samples. Enzyme-linked immunosorbent assay (ELISA) was conducted for measuring levels of corticosterone (CORT) and interleukin-1ß (IL-1ß) in sera, whereas levels of protein expression in colon and hippocampal tissues were examined by western blot. Faecal microbial communities were analysed by sequencing 16S rDNAs. RESULTS: Mice in CUMS and DEX groups exhibited severe depression-like behaviours. Compared with CON mice, CUMS-exposed mice showed a significant increase in both α and ß diversity. Prevotellaceae and Desulfovibrio were enriched, whereas Bacilli were decreased in the faeces of mice in the CUMS group. DEX-treated mice had a decrease in the abundance of Clostridium XVIII. Levels of occludin in colon tissue of DEX-treated mice were reduced. Relative to mice in the CON and CUMS groups, DEX-treated mice contained higher serum levels of CORT and IL-1ß. Compared with CON mice, mice in the DEX and CUMS groups had higher levels of IL-1ß in sera and lower levels of glial fibrillary acidic protein (GFAP), Nestin, Synapsin-1 and P2Y12 receptor in the hippocampus. CONCLUSIONS: Changes of gut microbiota diversity, intestinal integrity and neuroinflammation in the brain contribute to CUMS-induced depression, whereas pathobionts and excessive immunosuppression with damaged neuronal synapses is a basis of the DEX-induced depression.