Mutation to a cytochrome P450 -like gene alters the leaf color by affecting the heme and chlorophyll biosynthesis pathways in Brassica napus.

The regulated biosynthesis of chlorophyll is important because of its effects on plant photosynthesis and dry biomass production. In this study, a map-based cloning approach was used to isolate the cytochrome P450 -like gene BnaC08g34840D (BnCDE1) from a chlorophyll-deficient mutant (cde1) of Brassica napus obtained by ethyl methanesulfonate (EMS) mutagenization. Sequence analyses revealed that BnaC08g34840D in the cde1 mutant (BnCDE1I320T ) encodes a substitution at amino acid 320 (Ile320Thr) in the conserved region. The over-expression of BnCDE1I320T in ZS11 (i.e., gene-mapping parent with green leaves) recapitulated a yellow-green leaf phenotype. The CRISPR/Cas9 genome-editing system was used to design two single-guide RNAs (sgRNAs) targeting BnCDE1I320T in the cde1 mutant. The knockout of BnCDE1I320T in the cde1 mutant via a gene-editing method restored normal leaf coloration (i.e., green leaves). These results indicate that the substitution in BnaC08g34840D alters the leaf color. Physiological analyses showed that the over-expression of BnCDE1I320T leads to decreases in the number of chloroplasts per mesophyll cell and in the contents of the intermediates of the chlorophyll biosynthesis pathway in leaves, while it increases heme biosynthesis, thereby lowering the photosynthetic efficiency of the cde1 mutant. The Ile320Thr mutation in the highly conserved region of BnaC08g34840D inhibited chlorophyll biosynthesis and disrupted the balance between heme and chlorophyll biosynthesis. Our findings may further reveal how the proper balance between the chlorophyll and heme biosynthesis pathways is maintained.

White matter hyperintensity burden and collateral circulation in acute ischemic stroke with large artery occlusion.

OBJECTIVE: This study aimed to investigate the association between white matter hyperintensity (WMH) burden and pial collaterals in acute strokes caused by intracranial large artery occlusion treated with mechanical thrombectomy in the anterior circulation, focusing on stroke subtypes. METHODS: Consecutive patients undergoing mechanical thrombectomy between December 2019 and June 2022 were retrospectively screened. The Fazekas scale assessed WMH burden. Pial collaterals were categorized as either poor (0-2) or good (3-4) based on the Higashida score. A multivariable analysis was used to determine the relationship between WMH burden and pial collaterals. Subgroup analyses delved into associations stratified by stroke subtypes, namely cardioembolism (CE), tandem lesions (TLs), and intracranial atherosclerosis (ICAS). RESULTS: Of the 573 patients included, 274 (47.8%) demonstrated poor pial collaterals. Multivariable regression indicated a strong association between extensive WMH burden (Fazekas score of 3-6) and poor collaterals [adjusted OR 3.04, 95% CI 1.70-5.46, P < 0.001]. Additional independent predictors of poor collaterals encompassed ICAS-related occlusion (aOR 0.26, 95% CI 0.09-0.76, P = 0.014), female sex (aOR 0.63, 95% CI 0.41-0.96, P = 0.031), and baseline Alberta Stroke Program Early Computed Tomography scores (aOR 0.80, 95% CI 0.74-0.88, P < 0.001). Notably, an interaction between extensive WMH burden and stroke subtypes was observed in predicting poor collaterals (P = 0.001), being pronounced for CE (adjusted OR 2.30, 95% CI 1.21-4.37) and TLs (adjusted OR 5.09, 95% CI 2.32-11.16), but was absent in ICAS (adjusted OR 1.24, 95% CI 0.65-2.36). CONCLUSIONS: Among patients treated with mechanical thrombectomy for anterior circulation large artery occlusion, extensive WMH burden correlates with poor pial collaterals in embolic occlusion cases (CE and TLs), but not in ICAS-related occlusion.

Remote preparation and manipulation of squeezed light.

Remote state preparation enables one to create and manipulate a quantum state based on the shared entanglement between distant nodes. Here, we experimentally demonstrate remote preparation and manipulation of squeezed light. By performing a homodyne projective measurement on one mode of the continuous variable entangled state at Alice's station, a squeezed state is created at Bob's station. Moreover, rotation and displacement operations are applied on the prepared squeezed state by changing the projective parameters on Alice's state. We also show that the remotely prepared squeezed state is robust against loss and N - 1 squeezed states can be remotely prepared based on an N-mode continuous variable Greenberger-Horne-Zeilinger-like state. Our results verify the entanglement-based model used in security analysis of quantum key distribution with continuous variables and have potential application in remote quantum information processing.

Experimental Demonstration of Remotely Creating Wigner Negativity via Quantum Steering.

Non-Gaussian states with Wigner negativity are of particular interest in quantum technology due to their potential applications in quantum computing and quantum metrology. However, how to create such states at a remote location remains a challenge, which is important for efficiently distributing quantum resource between distant nodes in a network. Here, we experimentally prepare an optical non-Gaussian state with negative Wigner function at a remote node via local non-Gaussian operation and shared Gaussian entangled state existing quantum steering. By performing photon subtraction on one mode, Wigner negativity is created in the remote target mode. We show that the Wigner negativity is sensitive to loss on the target mode, but robust to loss on the mode performing photon subtraction. This experiment confirms the connection between the remotely created Wigner negativity and quantum steering. As an application, we present that the generated non-Gaussian state exhibits metrological power in quantum phase estimation.

Informed Attentive Predictors: A Generalisable Architecture for Prior Knowledge-Based Assisted Diagnosis of Cancers.

Due to the high mortality of many cancers and their related diseases, the prediction and prognosis techniques of cancers are being extensively studied to assist doctors in making diagnoses. Many machine-learning-based cancer predictors have been put forward, but many of them have failed to become widely utilised due to some crucial problems. For example, most methods require too much training data, which is not always applicable to institutes, and the complicated genetic mutual effects of cancers are generally ignored in many proposed methods. Moreover, a majority of these assist models are actually not safe to use, as they are generally built on black-box machine learners that lack references from related field knowledge. We observe that few machine-learning-based cancer predictors are capable of employing prior knowledge (PrK) to mitigate these issues. Therefore, in this paper, we propose a generalisable informed machine learning architecture named the Informed Attentive Predictor (IAP) to make PrK available to the predictor's decision-making phases and apply it to the field of cancer prediction. Specifically, we make several implementations of the IAP and evaluate its performance on six TCGA datasets to demonstrate the effectiveness of our architecture as an assist system framework for actual clinical usage. The experimental results show a noticeable improvement in IAP models on accuracies, f1-scores and recall rates compared to their non-IAP counterparts (i.e., basic predictors).

Gated Graph Attention Network for Cancer Prediction.

With its increasing incidence, cancer has become one of the main causes of worldwide mortality. In this work, we mainly propose a novel attention-based neural network model named Gated Graph ATtention network (GGAT) for cancer prediction, where a gating mechanism (GM) is introduced to work with the attention mechanism (AM), to break through the previous work's limitation of 1-hop neighbourhood reasoning. In this way, our GGAT is capable of fully mining the potential correlation between related samples, helping for improving the cancer prediction accuracy. Additionally, to simplify the datasets, we propose a hybrid feature selection algorithm to strictly select gene features, which significantly reduces training time without affecting prediction accuracy. To the best of our knowledge, our proposed GGAT achieves the state-of-the-art results in cancer prediction task on LIHC, LUAD, KIRC compared to other traditional machine learning methods and neural network models, and improves the accuracy by 1% to 2% on Cora dataset, compared to the state-of-the-art graph neural network methods.

Image-Based Automatic Watermeter Reading under Challenging Environments.

With the rapid development of artificial intelligence and fifth-generation mobile network technologies, automatic instrument reading has become an increasingly important topic for intelligent sensors in smart cities. We propose a full pipeline to automatically read watermeters based on a single image, using deep learning methods to provide new technical support for an intelligent water meter reading. To handle the various challenging environments where watermeters reside, our pipeline disentangled the task into individual subtasks based on the structures of typical watermeters. These subtasks include component localization, orientation alignment, spatial layout guidance reading, and regression-based pointer reading. The devised algorithms for orientation alignment and spatial layout guidance are tailored to improve the robustness of our neural network. We also collect images of watermeters in real scenes and build a dataset for training and evaluation. Experimental results demonstrate the effectiveness of the proposed method even under challenging environments with varying lighting, occlusions, and different orientations. Thanks to the lightweight algorithms adopted in our pipeline, the system can be easily deployed and fully automated.

The Carbohydrate Metabolism of Lactiplantibacillus plantarum.

Lactiplantibacillus plantarum has a strong carbohydrate utilization ability. This characteristic plays an important role in its gastrointestinal tract colonization and probiotic effects. L. plantarum LP-F1 presents a high carbohydrate utilization capacity. The genome analysis of 165 L. plantarum strains indicated the species has a plenty of carbohydrate metabolism genes, presenting a strain specificity. Furthermore, two-component systems (TCSs) analysis revealed that the species has more TCSs than other lactic acid bacteria, and the distribution of TCS also shows the strain specificity. In order to clarify the sugar metabolism mechanism under different carbohydrate fermentation conditions, the expressions of 27 carbohydrate metabolism genes, catabolite control protein A (CcpA) gene ccpA, and TCSs genes were analyzed by quantitative real-time PCR technology. The correlation analysis between the expressions of regulatory genes and sugar metabolism genes showed that some regulatory genes were correlated with most of the sugar metabolism genes, suggesting that some TCSs might be involved in the regulation of sugar metabolism.

Deterministic Distribution of Multipartite Entanglement and Steering in a Quantum Network by Separable States.

As two valuable quantum resources, Einstein-Podolsky-Rosen entanglement and steering play important roles in quantum-enhanced communication protocols. Distributing such quantum resources among multiple remote users in a network is a crucial precondition underlying various quantum tasks. We experimentally demonstrate the deterministic distribution of two- and three-mode Gaussian entanglement and steering by transmitting separable states in a network consisting of a quantum server and multiple users. In our experiment, entangled states are not prepared solely by the quantum server, but are created among independent users during the distribution process. More specifically, the quantum server prepares separable squeezed states and applies classical displacements on them before spreading out, and users simply perform local beam-splitter operations and homodyne measurements after they receive separable states. We show that the distributed Gaussian entanglement and steerability are robust against channel loss. Furthermore, one-way Gaussian steering is achieved among users that is useful for further directional or highly asymmetric quantum information processing.

LncRNA MEG3 inhibits the inflammatory response of ankylosing spondylitis by targeting miR-146a.

Ankylosing spondylitis (AS) is a progressive systemic disease characterized by chronic inflammation response of the sacroiliac joint and spine. Long non-coding RNAs (lncRNAs) are widely involved in the regulation of various diseases. However, the role of lncRNA maternally expressed gene 3 (MEG3) in the inflammatory response of AS has not been studied. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of inflammatory cytokines interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in tissues and cells. The expression levels of MEG3, microRNA-146a (miR-146a), and inflammatory cytokines were measured by quantitative real-time PCR (qRT-PCR). Correlation between MEG3 or miR-146a and inflammatory cytokines was analyzed by Pearson analysis. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to clarify the interaction between MEG3 and miR-146a. MEG3 was downregulated in AS patients, negatively correlated with the levels of IL-1ß, IL-6, and TNF-α, and blocked the inflammatory response of AS. MiR-146a was upregulated in AS patients and could interact with MEG3. The expression of miR-146a was positively correlated with IL-1ß, IL-6, and TNF-α levels. Overexpression of miR-146a reversed the inhibitory effect of abnormal MEG3 expression on inflammatory cytokines. LncRNA MEG3 plays an anti-inflammatory role in AS partially through targeting miR-146a, which provides a potential new means for the treatment of AS patients.

Automatic epileptic seizure detection in EEGs using MF-DFA, SVM based on cloud computing.

BACKGROUND: Epilepsy is a chronic disease with transient brain dysfunction that results from the sudden abnormal discharge of neurons in the brain. Since electroencephalogram (EEG) is a harmless and noninvasive detection method, it plays an important role in the detection of neurological diseases. However, the process of analyzing EEG to detect neurological diseases is often difficult because the brain electrical signals are random, non-stationary and nonlinear. OBJECTIVE: In order to overcome such difficulty, this study aims to develop a new computer-aided scheme for automatic epileptic seizure detection in EEGs based on multi-fractal detrended fluctuation analysis (MF-DFA) and support vector machine (SVM). METHODS: New scheme first extracts features from EEG by MF-DFA during the first stage. Then, the scheme applies a genetic algorithm (GA) to calculate parameters used in SVM and classify the training data according to the selected features using SVM. Finally, the trained SVM classifier is exploited to detect neurological diseases. The algorithm utilizes MLlib from library of SPARK and runs on cloud platform. RESULTS: Applying to a public dataset for experiment, the study results show that the new feature extraction method and scheme can detect signals with less features and the accuracy of the classification reached up to 99%. CONCLUSIONS: MF-DFA is a promising approach to extract features for analyzing EEG, because of its simple algorithm procedure and less parameters. The features obtained by MF-DFA can represent samples as well as traditional wavelet transform and Lyapunov exponents. GA can always find useful parameters for SVM with enough execution time. The results illustrate that the classification model can achieve comparable accuracy, which means that it is effective in epileptic seizure detection.

Explicit memory and implicit memory in occipital lobe stroke patients.

BACKGROUND: Occipital stroke patients mainly showed cortical blindness and unilateral vision loss; memory is generally reserved. Recent reports from neuroimaging show the occipital lobe may be involved in the processing of implicit memory (IM), especially the perception type of IM processing. In this study, we explored the explicit memory (EM) and IM damage in occipital lobe stroke patients. METHODS: A total of 25 occipital strokes and 29 years of age, educational level equivalent healthy controls (HCs), evaluated by using immediate recall, delayed recall, recognition for EM tasks, picture identification, and category exemplar generation for IM tasks. RESULTS: There was no significant difference between occipital stroke patients and HCs in EM tasks and category exemplar generation task. In the picture identification task, occipital lobe stroke group score was poorer than HC group, the results were statistically significant, but in the pictures identify rate, occipital stroke patients and normal control group had no significant difference. CONCLUSIONS: The occipital stroke patients may have IM damage, primarily damage the perception type of IM priming effects, which was unrelated with their cortical blindness.

[Morphological assessment of sulfur mustard-induced acute lung injury in rats through different routes].

OBJECTIVE: To establish an animal model of sulfur mustard (SM)-induced acute lung injury in rats through different routes and compare the morphological changes in lung tissue and cells. METHODS: One hundred and thirty-six male rats were selected and randomly divided into 5 groups, namely peritoneal cavity SM group (n=32), trachea SM group (n=32), peritoneal cavity propylene glycol group (n=32), trachea propylene glycol group (n=32), and normal control group (n=8). The rats in peritoneal cavity SM group were injected intraperitoneally with diluted SM (0.1 ml, 8 mg/kg), and the rats in trachea SM group were injected intratracheally with diluted SM (0.1 ml, 2 mg/kg). Once the rats were sacrificed at 6, 24, 48, and 72 h after SM treatment, morphological changes in lung tissue and cells were observed by light and electron microscopy. RESULTS: In the peritoneal cavity SM group, the epithelial cells of bronchioles maintained intact with increased exudate and bleeding in alveolar cavity and large areas of pulmonary consolidation under the light microscope. In the tracheal SM group, focal ulcer formed in the epithelial cells of bronchioles with increased exudate and bleeding in alveolar cavity, partial pulmonary consolidation, and compensatory emphysema in peripheral alveolar space under the light microscope. The alveolar interval areas were widened obviously in both groups in a time-dependent manner. Under the electron microscope, we observed local loss of cellular membrane in type I alveolar epithelium, broken or lost microvilli in cells of typeⅡalveolar epithelium and fuzzy mitochondrial crista as well as the appearance of ribosome detached from rough endoplasmic reticulum in both two groups. Compared with those in the trachea SM group and the control group, the ratio of the alveolar septum average area to the visual field area in the peritoneal cavity SM group at 6, 24, 48, and 72 h was significantly higher (P<0.05). CONCLUSION: The lung tissue injury through the intraperitoneal route is more severe than that through the tracheal route, while focal ulceration of bronchioles epithelial cells appears in the case of tracheal route. The degree of injury increases over time in both groups, and the cellular damage is approximately the same in both groups.

Single frequency Ti:sapphire laser with continuous frequency-tuning and low intensity noise by means of the additional intracavity nonlinear loss.

A single frequency Ti:sapphire (Ti:S) laser with continuous frequency-tuning and low intensity noise is presented, in which an extra nonlinear (NL) loss crystal is placed inside the resonator instead of the traditional etalon locking system. When a NL crystal is inserted into a home-made Ti:S laser resonator, the single frequency laser of 1.27 W at 795 nm with a continuous frequency-tuning range of 48 GHz is realized under the pump level of 11.27 W and the intensity noise at the lower frequencies is successfully suppressed.

The association between intensity-specific physical activity and the number of multiple chronic diseases among Chinese elderly: A study based on the China Health and Retirement Longitudinal study (CHARLS).

Background: With ageing, the elderly are facing a complex situation where multiple chronic diseases coexist. This paper aims to investigate the effect of intensity-specific physical activity on the number of multiple chronic diseases in the elderly. Methods: Our data came from wave 4 of the China Health and Retirement Longitudinal Survey (CHARLS), which involved 10,341 residents aged ≥ 60 years. The intensity-specific physical activity was divided into two categories: moderate-intensity physical activity (MPA) lasting ≥ 150 min/week and vigorous-intensity physical activity (VPA) lasting ≥ 75 min/week. Data on 14 types of chronic diseases were collected. Propensity score matching (PSM) with controlling nine confounding factors were used to analyse the effects of intensity-specific physical activity. Results: Among 10,341 samples, 40.12% of the elderly often participated in MPA and 25.72% participated in VPA. The PSM results showed that performing 150 min/week of MPA leads to 0.0675(P<0.05) fewer multiple chronic diseases than not achieving this standard, and VPA up to 75 min/week leads to 0.0785(P<0.05) fewer multiple chronic disease than that does not meet this criterion. Additionally, VPA is more effective than MPA. Conclusion: Both MPA of at least 150 min/week and VPA of at least 75 min/week can significantly reduce the number of multiple chronic diseases in elderly. Elderly people should increase their exercise intensity as much as possible while ensuring safety.

Complete genome sequence of Erwinia amylovora PBI209 isolated from a necrotic flower of Pyrus sinkiangensis in China.

Here, we report the complete genome sequence of Erwinia amylovora PBI209 that causes fire blight isolated from a necrotic flower of Pyrus sinkiangensis in Xinjiang, China. The genome consists of 3,800,955 bp, with 3,403 protein-coding genes and a guanine-cytosine content of 53.61%.

Comparison of ASSR and frequency specificity ABR induced by NB CE-Chirp for prediction of behavioral hearing thresholds in children with conductive hearing loss.

BACKGROUND: Electrophysiological tests are often used to evaluate hearing loss in infants and young children with conductive hearing loss, no matter to quantify or characterize. However, there are advantages and disadvantages associated with the various electrophysiological tests that are currently available. Therefore, there is no gold standard test. This study aimed to compare the value of narrow-band (NB) CE-Chirp-induced auditory steady-state response (ASSR) and auditory brainstem response (ABR) for assessing hearing thresholds in children with conductive hearing loss. We hope to identify an effective electrophysiological testing method to evaluate conductive hearing loss and provide a reference for clinical hearing assessment of infants with conductive hearing loss. SUBJECTS: and Methods: We selected 27 children (41 ears) aged 3-6 years with otitis media with effusion (OME). Within 1 day, they underwent behavioral audiometry and NB CE-Chirp-induced ASSR and ABR tests in sequence. Pearson's correlation analysis was performed to compare behavioral audiometry thresholds and ASSR and ABR response thresholds at 500, 1000, 2000, and 4000 Hz. RESULTS: The behavioral audiometry thresholds of all children were strongly correlated with the response thresholds of the two electrophysiological tests, with correlation coefficients of 0.659, 0.605, 0.723, and 0.857 for ASSR, and 0.587, 0.684, 0.753, and 0.802 for ABR. The proportion of children with a difference of ≤10 dB between ASSR and behavioral audiometry thresholds or between ABR and behavioral audiometry thresholds was not high, especially in the low frequencies. ABR results were superior to ASSR results in terms of predicting actual hearing levels. At 0.5, 1, 2, and 4 kHz, the average differences between the behavioral hearing thresholds and ASSR thresholds in the 41 ears were 5.6, 5.7, 2, and 5.6 dB, respectively. The average differences between behavioral hearing thresholds and ABR thresholds was -5.6, -1.4, -6.8, and 3.2 dB, respectively. The hearing loss configuration of the ASSR exhibited a peaked pattern, similar to behavioral audiometry, whereas the ABR exhibited an ascending pattern. The time to perform the single-ear ASSR test was 5.9 min, whereas the ABR test took 17.0 min. CONCLUSION: ASSR and ABR induced by the NB CE-Chirp correlated well with behavioral audiometry in children with conductive hearing loss. The NB CE-Chirp ASSR has advantages in terms of testing time and hearing configuration evaluation, whereas ABR has better reliability than ASSR. However, the stability of ASSR and ABR induced by the NB CE-Chirp is poor, and the thresholds obtained cannot replace behavioral audiometry in evaluating the true hearing of children with conductive hearing loss. However, ASSR and ABR can be used as auxiliary tests for cross-validation.

Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of KMT2D-related Kabuki syndrome.

BACKGROUND: Kabuki syndrome 1 (KS1; OMIM:147920), which is characterized by distinctive dysmorphic facial features (such as arched eyebrows, long palpebral fissures with eversion of the lower lid, and large protuberant ears), intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities, is brought on by pathogenic variants in KMT2D (OMIM:602113). In this work, three individuals with novel pathogenic KMT2D gene variants had their longitudinal audiological manifestations and ear structural characteristics outlined. METHODS: The longitudinal audiological data from neonatal hearing screening and a battery of several hearing tests were evaluated. The battery of hearing tests included tympanometry, distortion product otoacoustic emission (DPOAE), click-evoked air-conduction auditory brain-stem response (AC-ABR), click-evoked bone-conduction auditory brain-stem response (BC-ABR), narrow band CE-chirp auditory steady-state response (NB CE-chirp ASSR), and pure-tone audiometry (PTA). Phenotype identification and whole exome sequencing (WES) were performed on recruited individuals. RESULTS: All three patients (two females and on male; last evaluations at 14 months, 11 months, and 5.7 years, respectively) failed the newborn hearing screening, and the audiological follow-up data revealed mild to profound fluctuating hearing loss, which was directly influenced by the incidence and severity of otitis media with effusion (OME). When OME occurred, the AC-ABR thresholds increased from 30-75 dBnHL to 45-90 dBnHL. The threshold for the BC-ABR and BC-PTA was between 25 and 50 dBnHL, indicating mild to moderate sensorineural hearing loss (SNHL). The high-resolution computed tomography (HRCT) pictures indicated that all three patients had middle and inner ear abnormalities. Middle ear anomalies showed as diminished mastoid gasification and ossicle dysplasia. Cochlear dysplasia, a dilated vestibule, fusion of the vestibule with the horizontal semicircular canals, and a short and thick horizontal semicircular canal were visible on images of the inner ear. This study recruited three individuals with three novel pathogenic variants (c.5104C>T, c.10205delA, and c.12840delC) of KMT2D who were identified at ages 27 days, 2 months, and 5.5 years. CONCLUSIONS: Hearing characteristics of three individuals with three novel pathogenic variants of KMT2D range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.

A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms.

Background: Exophytic papillary urothelial neoplasms (EPUN) are difficult to diagnose pathologically and are well-known for their heterogeneous prognoses. Thus, searching for an objective and accurate diagnostic marker is of great clinical value in improving the outcomes of EPUN patients. PHH3 was reported to be expressed explicitly in the mitotic phase of the cell cycle, and recent studies have shown that PHH3 expression was associated with the differential diagnosis and prognosis of many tumors. However, its significance in EPUN remains unclear. This study aimed to determine the expression of PHH3 in different EPUN, compare its expression with cell-cycle related proteins Ki67 and P53, and analyze its significance in the differential diagnosis and prognostic value for high-grade papillary urothelial carcinoma (HGPUC), low-grade papillary urothelial carcinoma (LGPUC), papillary urothelial neoplasm of low malignant potential (PUNLMP) and urothelial papilloma (UP). Methods: We retrospectively analyzed the pathological diagnosis and clinical features of 26 HGPUC cases, 43 LGPUC cases, 21 PUNLMP cases and 11 UP cases. PHH3, Ki67 and P53 were detected by immunohistochemistry in 101 EPUN cases samples. The cut-off values of PHH3 mitosis count (PHMC), HE mitosis count (HEMC), Ki67 and P53 in the different EPUN were determined using the ROC curve. The distribution of counts in each group and its relationship with clinical parameters and prognosis of EPUN patients were also analyzed. Results: The determination coefficient (R2 = 0.9980) of PHMC were more potent than those of HEMC (R2 = 0.9734) in the EPUN mitotic counts microscopically by both pathologists. Of the 101 EPUN cases investigated, significant positive linear correlations were found between PHMC and HEMC, PHMC and Ki67, and HEMC and Ki67 (P < 0.0001). In HGPUC, LGPUC, PUNLMP and UP, a decreasing trend was observed in the median and range of PHMC/10HPFs, HEMC/10HPFs, Ki67 (%) and P53 (%). PHMC, HEMC, Ki67 and P53 were associated with different clinical parameters of EPUN. PHMC, HEMC, Ki67 and P53 were found to exhibit substantial diagnostic values among different EPUN and tumor recurrence. Based on the ROC curve, when PHMC was >48.5/10HPFs, a diagnosis of HGPUC was more likely, and when PHMC was >13.5/10HPFs, LGPUC was more likely. In addition, when PHMC was >5.5/10HPFs, the possibility of non-infiltrating LGPUC was greater. Kaplan-Meier survival curve analysis showed that the median recurrence-free survival (RFS) for cases with PHMC > 13.5/10HPFs and HEMC > 14.5/10HPFs were 52.5 and 48 months, respectively, and their respective hazard ratio was significantly higher (Log-rank P < 0.05). Conclusion: PHH3 exhibited high specificity and sensitivity in diagnosing EPUN. Combined with HEMC, Ki67 and P53, it can assist in the differential diagnosis of EPUN and estimate its clinical progression with high predictive value to a certain extent.

[Regularity of meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea and secondary dysmenorrhea patients].

OBJECTIVE: To observe the meridian-acupoint reactions of foot three yin meridians in primary dysmenorrhea(PD) and secondary dysmenorrhea(SD) patients, so as to summarize the rules of meridian-acupoint reaction and acupoints selection. METHODS: Thirty-five patients with PD (PD group), 34 patients with SD (SD group) and 35 healthy subjects (healthy group) were recruited. The compression method was used to examine the lower leg segment of the foot three yin meridians. Positive reactions(palpable skin changes, including cords, nodules, depressions) and tenderness of meridians and acupoints were recorded. The visual analogue scale (VAS) was used to evaluate the tenderness severity of acupoints. RESULTS: Compared with the healthy group, the probability of positive reactions and tenderness in foot three yin meridians were higher in PD and SD groups (P<0.01,P<0.05). Compared with the PD group, the probability of positive reactions in Spleen and Liver Meridians were higher in the SD group, with higher probability of tenderness in Liver Meridian(P<0.05). The probability of positive reactions and tenderness in the Spleen Meridian of PD and SD groups was significantly higher than that in the Kidney Meridian (P<0.01), while the probability of tenderness in the Spleen Meridian of the PD group was significantly higher than that in the Liver Meridian (P<0.05). Positive reactions and tenderness were concentrated at Yinlingquan (SP9), Diji (SP8) and Sanyinjiao (SP6) of Spleen Meridian and Xiguan (LR7) and Ligou (LR5) in Liver Meridian of PD and SD groups. In comparison with the PD group, the probability of positive reactions, tenderness and VAS score of SP8 and LR5 of the SD group were higher (P<0.05, P<0.01). CONCLUSION: The positive reaction occurs most frequently in the Spleen Meridian, followed by the Liver Meridian, and least frequently in the Kidney Meridian. The acupoints with positive reaction are different between PD and SD, which suggests that the Spleen Meridian acupoints should be the main acupoints when treating the two kinds of dysmenorrhea, and acupoints should also be selected according to the meridian and acupoint examination results.