Morphological study of CT image of posterior pilon variant fracture and its possible clinical significance.

OBJECTIVE: The incidence of posterior pilon variant fractures has been underestimated. The purpose was to study the characteristics of posteromedial (PM) and posterolateral (PL) fragments in CT imaging of posterior pilon variant fractures, and to provide help for clinical diagnosis and treatment. METHODS: CT imaging data of 109 cases of posterior pilon variant fractures in our hospital from January 2013 to December 2020 were retrospectively analyzed. According to Mason and Molloy classification, PM fragments were further divided into pilon subtypes and avulsed subtypes. The largest actual area of fragments in axial and sagittal were selected as the study plane, and the maximum axial lengths of X, Y and Z, α angle, ß angle, fragment area (S1-7) and fragment area ratio (FAR1-4), interfragmentary (IF) angle, and back of tibia (BT) angle were measured. RESULTS: A total of 109 cases were included in this study, 61 of whom were pilon subtypes [90.16% were supination-external rotation (SER) injuries]. 48 cases were avulsed subtypes [81.25% were pronation-external rotation (PER) injuries]. Pilon subtypes were larger than avulsed subtypes in X, Y, Z, α2 Angle, ß2 Angle, fragment area and ratio, and IF and BT angle (P < 0.05). There was no difference between α1 and ß1 angle (P > 0.05). CONCLUSION: The morphology of pilon subtype was larger than that of avulsion subtype. According to fragment size, morphology, and injury mechanism, two fragments of pilon subtype should be anatomic reduction and fixation. However, the PL fragment of avulsion subtype should to be fixed, while PM fragment may only need conservative treatment.

Globally optimal OCT surface segmentation using a constrained IPM optimization.

Segmentation of multiple surfaces in optical coherence tomography (OCT) images is a challenging problem, further complicated by the frequent presence of weak boundaries, varying layer thicknesses, and mutual influence between adjacent surfaces. The traditional graph-based optimal surface segmentation method has proven its effectiveness with its ability to capture various surface priors in a uniform graph model. However, its efficacy heavily relies on handcrafted features that are used to define the surface cost for the "goodness" of a surface. Recently, deep learning (DL) is emerging as a powerful tool for medical image segmentation thanks to its superior feature learning capability. Unfortunately, due to the scarcity of training data in medical imaging, it is nontrivial for DL networks to implicitly learn the global structure of the target surfaces, including surface interactions. This study proposes to parameterize the surface cost functions in the graph model and leverage DL to learn those parameters. The multiple optimal surfaces are then simultaneously detected by minimizing the total surface cost while explicitly enforcing the mutual surface interaction constraints. The optimization problem is solved by the primal-dual interior-point method (IPM), which can be implemented by a layer of neural networks, enabling efficient end-to-end training of the whole network. Experiments on spectral-domain optical coherence tomography (SD-OCT) retinal layer segmentation demonstrated promising segmentation results with sub-pixel accuracy.

Spontaneous Ventilation Video-Assisted Thoracoscopic Surgery for Geriatric Patients With Non-Small-Cell Lung Cancer.

OBJECTIVES: The aim of the present study was to compare the short-term outcomes between spontaneous ventilation video-assisted thoracic surgery (SV-VATS) and mechanical ventilation video-assisted thoracic surgery (MV-VATS) in the elderly. All patients included in the present study underwent lobectomy, segmentectomy, or wedge resection and lymph node dissection. DESIGN: A retrospective cohor. SETTING: The first affiliated hospital of Guangzhou Medical University, Guangzhou, China. PARTICIPANTS: The present study included 799 elderly patients diagnosed with non-small-cell lung cancer undergoing SV-VATS or MV-VATS. After propensity score matching, 80 patients in the SV-VATS group and 80 patients in the MV-VATS group were analyzed. INTERVENTIONS: Patients in the SV-VATS group received spontaneous-ventilation anesthesia, which was administered as follows: intravenous anesthesia + laryngeal mask airway + thoracic paravertebral block + visceral pleural surface anesthesia + thoracic vagus nerve block. Patients in the MV-VATS group received general endotracheal anesthesia. SV-VATS or MV-VATS was performed according to the preference of the patients. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in anesthesia time (226.3 ± 79.8 v 238.5 ± 66.2 min; p = 0.44), surgery time (166.2 ± 102.6 v 170.1 ± 83.4 min; p = 0.66), and number of dissected lymph nodes (5.3 ± 7.5 v 4.4 ± 7.4; p = 0.23) between the two groups. There were significant differences in intraoperative bleeding (61.5 ± 165.1 v 82.2 ± 116.9 mL; p < 0.001). After surgery, the two groups were statistically comparable in terms of hospitalization (17.6 ± 7.6 v 17.2 ± 6.9 days; p = 0.95) and incidence of complications (7.5% v 13.8%; p = 0.20), while there were significant differences in chest tube duration (6.1 ± 3.3 v 4.5 ± 1.2 days; p < 0.001). CONCLUSIONS: SV-VATS is feasible and as safe as MV-VATS, and it could be considered as an alternative treatment for the elderly.

KLF5-mediated Eppk1 expression promotes cell proliferation in cervical cancer via the p38 signaling pathway.

BACKGROUND: Epiplakin1 (Eppk1) is part of epidermal growth factor (EGF) signal and takes part in reorganization of cytoskeleton and cell proliferation. However, the role of Eppk1 in cervical cancer (CC) remains unknown. METHODS: To express Eppk1 and KLF5 and their correlation, we used RNA-sequence, RT-qPCR, TCGA database and immunofluorescence staining in vitro and in different pathological cervical tissues. In CC cell lines, we tested adenovirus-mediated over expression or knockdown of KLF5 and siRNA-mediated knockdown of Eppk1 and a suiting assessment of cell proliferation and cell signaling by western blot and CCK8 tests. We studied the mechanism by which KLF5 regulates Eppk1 expression by reporter gene test and chromatin immunoprecipitation test. RESULTS: Eppk1 expression promoted in CC tissues and cell lines compared with increased KLF5 expression. The results of immunofluorescence staining further showed the increased co-expression of Eppk1 and KLF5 correlated substantially with tumorigenesis in cervical tissues. Overexpression of KLF5 significantly increased Eppk1 expression at transcription and translation levels. Conversely, the knockdown of KLF5 by siRNA against KLF5 decreased Eppk1 expression. Mechanically, KLF5 activated Eppk1 transcription by direct binding to the Eppk1 promoter. Gain- and loss-of-function experiments reported that KLF5 promoted cell proliferation in Hela partly dependent on Eppk1 upregulation. Besides, KLF5-mediated activation of p38 signaling significantly decreased after Eppk1 knockdown compared with decline of proliferation, suggesting that Eppk1 lies upstream of p38 signaling affecting cell proliferation. Finally, Eppk1 expression is positively correlated with tumor size in clinicopathological features of CC. CONCLUSIONS: Eppk1 may be an effective therapeutic target for affecting p38 signaling pathway and cell proliferation in cervical cancer.

Lipin1 mediates cognitive impairment in fld mice via PKD-ERK pathway.

Lipin1 is important in lipid synthesis because of its phosphatidate phosphatase activity, and it also functions as transcriptional coactivators to regulate the expression of genes involved in lipid metabolism. We found that fld mice exhibit cognitive impairment, and it is related to the DAG-PKD-ERK pathway. We used fld mice to explore the relationship between lipin1 and cognitive function. Our results confirmed the presence of cognitive impairment in the hippocampus of lipin1-deficient mice. As shown in behavioral test, the spatial learning and memory ability of fld mice was much worse than that of wild-type mice. Electron microscopy results showed that the number of synapses in hippocampus of fld mice was significantly reduced. BDNF,SYP, PSD95 were significantly reduced. These results suggest that lipin1 impairs synaptic plasticity. Hence,a deficiency of lipin1 leads to decreased DAG levels and inhibits PKD activation, thereby affecting the phosphorylation of ERK and the CREB.

Cross-resistance of the pathogenic fungus Alternaria alternata to fungicides with different modes of action.

BACKGROUND: Cross-resistance, a phenomenon that a pathogen resists to one antimicrobial compound also resists to one or several other compounds, is one of major threats to human health and sustainable food production. It usually occurs among antimicrobial compounds sharing the mode of action. In this study, we determined the sensitivity profiles of Alternaria alternata, a fungal pathogen which can cause diseases in many crops to two fungicides (mancozeb and difenoconazole) with different mode of action using a large number of isolates (234) collected from seven potato fields across China. RESULTS: We found that pathogens could also develop cross resistance to fungicides with different modes of action as indicated by a strong positive correlation between mancozeb and difenoconazole tolerances to A. alternata. We also found a positive association between mancozeb tolerance and aggressiveness of A. alternata, suggesting no fitness penalty of developing mancozeb resistance in the pathogen and hypothesize that mechanisms such as antimicrobial compound efflux and detoxification that limit intercellular accumulation of natural/synthetic chemicals in pathogens might account for the cross-resistance and the positive association between pathogen aggressiveness and mancozeb tolerance. CONCLUSIONS: The detection of cross-resistance among different classes of fungicides suggests that the mode of action alone may not be an adequate sole criterion to determine what components to use in the mixture and/or rotation of fungicides in agricultural and medical sects. Similarly, the observation of a positive association between the pathogen's aggressiveness and tolerance to mancozeb suggests that intensive application of site non-specific fungicides might simultaneously lead to reduced fungicide resistance and enhanced ability to cause diseases in pathogen populations, thereby posing a greater threat to agricultural production and human health. In this case, the use of evolutionary principles in closely monitoring populations and the use of appropriate fungicide applications are important for effective use of the fungicides and durable infectious disease management.

Deletion of the Riemerella anatipestifer type IX secretion system gene sprA results in differential expression of outer membrane proteins and virulence.

Riemerella anatipestifer (RA), the causative agent of infectious serositis that targets ducklings and other poultry, secretes protein via the type IX secretion system (T9SS). The proteins transported by T9SS are located on the bacterial cell surface or secreted into the extracellular milieu. In this study, a sprA deletion mutant was constructed encoding a core protein of T9SS to investigate its influence on outer membrane protein expression and its role in virulence. Compared with the wild-type RA-YM strain, the deletion mutant ΔsprA failed to digest gelatin, showed the same growth rate in the logarithmic phase and exhibited greater sensitivity to the bactericidal activity of duck sera, whereas the complemented strain restored these phenotypes. The outer membrane proteome of RA-YM and the ΔsprA mutant were analyzed by Tandem Mass Tags, which revealed 198 proteins with predicted localization to the cell envelope. Sixty-three of these proteins were differentially expressed in the outer membrane, with 43 up-regulated and 20 down-regulated. Among the twelve outer membrane proteins which were secreted by T9SS, four proteins were up-regulated and one protein was down-regulated. Animal experiments demonstrated that the median lethal dose of the mutant strain ΔsprA was about 500 times higher than that of the wild-type RA-YM strain, and bacterial loads in blood, brain, heart, liver and spleen of the ΔsprA-infected ducks were significantly reduced. Our results indicate that the SprA is a virulence-associated factor of RA, and its absence results in altered abundance of outer membrane proteins, and secretion disorders associated with some of the T9SS effector proteins.

Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing.

Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.

Vaspin as a Risk Factor of Insulin Resistance in Obstructive Sleep Apnea-Hypopnea Syndrome in an Animal Model.

BACKGROUND: In this study, we aimed to establish a chronic intermittent hypoxia model in rats and explore the possible role of vaspin in insulin sensitivity. METHODS: Healthy male Wistar rats were randomly divided into two groups: normal control group (NC) and chronic intermittent hypoxia group (CIH). The NC group was raised under physiological conditions and the CIH group was kept in the plexiglass chamber between 9 am and 5 pm undergoing intermittent hypoxic challenge for 8 hours/day for 8 weeks. Arterial blood pressure of rats (tail cannulation) was measured before and after the study. Fasting plasma glucose (FPG), total cholesterol (TC), triglycerides (TG), fasting insulin (FINS), vaspin, and leptin levels were measured. Vaspin mRNA expression in visceral adipose tissues was measured with Real Time-PCR. The protein levels of vaspin, Akt and phospho-Akt in visceral tissues were determined by Western-blot. RESULTS: At baseline, all the measurements in the CIH and NC groups were comparable. By the end of the experiment, the blood pressure of the CIH group was significantly higher than the NC group. The levels of FPG, FINS, TG, TC, leptin, and vaspin in the CIH group were significantly higher than in NC group. Plasma vaspin levels were correlated with FINS, HOMA-IR, and TG levels. Vaspin expression in both mRNA and protein levels in visceral adipose tissues of the CIH group were clearly higher than the NC group. Phospho-Akt protein level was decreased in visceral adipose tissues of the CIH group compared to the NC group. CONCLUSIONS: In the chronic intermittent hypoxia rat model, the expression of vaspin in visceral adipose tissues and plasma were increased, which were correlated with insulin resistance.

Therapeutic Effect of Metformin on Chemerin in Non-Obese Patients with Non-Alcoholic Fatty Liver Disease (NAFLD).

BACKGROUND: Chemerin is an important risk factor of insulin resistance. Non-alcoholic fatty liver has typical characteristics of insulin resistance. The aim of this study was to explore the potential role of chemerin in NAFLD. METHODS: 45 subjects included 22 control subjects (A group) and 23 subjects diagnosed with non-alcoholic fatty liver disease (B group) participated in the study. 23 patients in the NAFLD group received oral daily metformin at a dose of 20 mg/kg/day for 24 weeks follow-up. Chemerin and insulin resistance markers were determined at baseline and 24 weeks. RESULTS: The levels of WHR, BMI, FINS, HOMA-IR, TG, ALT, AST, and Chemerin in B group were significantly higher than A group. After 24 weeks of metformin treatment, the levels of WHR, AST, ALT, TG, chemerin and HOMA-IR were significantly reduced (p < 0.05) and other indexes were not changed significantly. Correlation analysis indicated that serum chemerin concentrations were positively correlated with BMI, WHR, HOMA-IR, FINS, TG, ALT, and AST levels. Logistic regression analysis showed chemerin, TG, and ALT were independent variables associated with NAFLD. CONCLUSIONS: These findings showed a significant increase of chemerin level in NAFLD patients. Metformin treatment can improve NAFLD and decrease the level of chemerin. Chemerin, TG, and ALT were independent variables associated with NAFLD.

Novel mutations of the RS1 gene in a cohort of Chinese families with X-linked retinoschisis.

PURPOSE: X-linked retinoschisis is a retinal dystrophy caused by mutations in the RS1 gene in Xp22.1. These mutations lead to schisis (splitting) of the neural retina and subsequent reduction in visual acuity in affected men (OMIM # 312700). The aim of this study was to identify the RS1 gene mutations in a cohort of Chinese patients with X-linked retinoschisis, and to describe the associated phenotypes. METHODS: Patients and unaffected individuals from 16 unrelated families underwent detailed ophthalmic examinations. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. All exons including the exon-intron boundaries of the RS1 gene, were amplified by PCR and the products were analyzed by direct sequencing. Long-range PCR followed by DNA sequencing was used to define the breakpoints of the large deletion. RESULTS: Sixteen male individuals from 16 families were diagnosed with retinoschisis by clinical examination. The median age at review was 13.2 years (range: 5-34 years); the median best-corrected visual acuity upon review was 0.26 (range 0.02-1.0). Foveal schisis was found in 82.8% of the eyes (24/29) while peripheral schisis was present in 27.5% of the eyes (8/29). Sequencing of the RS1 gene identified 16 mutations, nine of which were novel. The mutations included eight missense mutations, all located in exons 4-6 (50.0%), two nonsense mutations (12.5%), four small deletions or insertions (25.0%), one splice site mutation (6.25%), and one large genomic deletion that included exon1 (6.25%). CONCLUSIONS: The mutations found in our study broaden the spectrum of RS1 mutations. The identification of the specific mutation in each pedigree will allow future determination of female carrier status for genetic counseling purposes.

Involvement of CSE/ H2S in high glucose induced aberrant secretion of adipokines in 3T3-L1 adipocytes.

BACKGROUND: Deregulated secretion of adipokines contributes to subclinical systemic inflammation associated with type 2 diabetes mellitus (T2DM). However, the mechanisms underlying are not fully understood. Hydrogen sulfide (H2S), as an endogenous gasotransmitter, possesses an anti-inflammation activity. The aim of this study was to examine the possible involvement of H2S in high glucose induced adipokine secretion in 3T3-L1 adipocytes. METHODS: The expression of cystathionine-gamma-lyase (CSE), the H2S-forming enzyme, was evaluated by Western-blotting and real-time PCR. The secretion of TNF-α, MCP-1 and adiponectin was determined by radioimmunoassay and enzyme-linked immunosorbent assay (ELISA), respectively. Lentiviral empty vector and vector expressing mouse CSE were used for in vitro transduction. RESULTS: High glucose (HG) significantly decreased CSE expression at both protein and mRNA levels in mature 3T3-L1 adipocytes. In parallel, HG significantly increased secretion of MCP-1 while decreasing secretion of adiponectin, but had no effect on secretion of TNF-α. HG induced changes in MCP-1 and adiponectin secretion were partly attenuated by forced expression of CSE or sodium hydrosulfide (NaHS), a source of exogenous H2S. CONCLUSION: High glucose induces aberrant secretion of adipokines in mature 3T3-L1 adipocytes, favoring inflammation. The mechanism is partly related to inhibition of CSE/ H2S system.

Simultaneous Resection of Colorectal Cancer and Liver Metastases through Hand-assisted Laparoscopic Surgery: Preliminary Exploration.

BACKGROUND/AIMS: To describe the initial experience of simultaneous resection of colorectal cancer and liver metastases through hand-assisted laparoscopy (HALS). METHODOLOGY: After endotracheal general anesthesia, patients were placed in the Trendelenburg with lithotomy position. A 5-cm longitudinal subumbilical port was created, and the Lap Disc device was placed and pneumoperitoneum was established. A laparoscope was inserted to explore the liver and the whole pelvic cavity. The surgeon stood on the right side or between the patient's legs, and a 10-mm trocar was placed in the abdominal wall based upon the location of the tumor. The liver and the colorectal lesion were reselected with the assisted-hand through the Lap Disc to establish the possibility of resection, the tumor margin, and metastasis. RESULTS: Simultaneous resection of colorectal cancer and liver metastases through HALS were successful in all eight patients with operating time of 2-4 h. Average intraoperative blood loss was 100-300 ml, and no severe postoperative complications were observed. The average length of postoperative hospital stay was 7.5 days. CONCLUSIONS: HALS for simultaneous resection of colorectal and metastatic liver cancer has the advantages of safety, feasibility, minimal invasion, shorter operation time, reduced operative difficulty less pain and rapid recovery.

Varied microbial community assembly and specialization patterns driven by early life microbiome perturbation and modulation in young ruminants.

Perturbations and modulations during early life are vital to affect gut microbiome assembly and establishment. In this study, we assessed how microbial communities shifted during calf diarrhea and with probiotic yeast supplementation (Saccharomyces cerevisiae var. boulardii, SCB) and determined the key bacterial taxa contributing to the microbial assembly shifts using a total of 393 fecal samples collected from 84 preweaned calves during an 8-week trial. Our results revealed that the microbial assembly patterns differed between healthy and diarrheic calves at 6- and 8-week of the trial, with healthy calves being stochastic-driven and diarrheic calves being deterministic-driven. The two-state Markov model revealed that SCB supplementation had a higher possibility to shift microbial assembly from deterministic- to stochastic-driven in diarrheic calves. Furthermore, a total of 23 and 21 genera were specific ecotypes to assembly patterns in SCB-responsive (SCB-fed calves did not exhibit diarrhea) and nonresponsive (SCB-fed calves occurred diarrhea) calves, respectively. Among these ecotypes, the area under a receiver operating characteristic curve revealed that Blautia and Ruminococcaceae UCG 014, two unidentified genera from the Ruminococcaceae family, had the highest predictiveness for microbial assembly patterns in SCB-responsive calves, while Prevotellaceae, Blautia, and Escherichia-Shigella were the most predictive bacterial taxa for microbial assembly patterns in SCB-nonresponsive calves. Our study suggests that microbiome perturbations and probiotic yeast supplementation serving as deterministic factors influenced assembly patterns during early life with critical genera being predictive for assembly patterns, which sheds light on mechanisms of microbial community establishment in the gut of neonatal calves during early life.

Chromosome-Scale Genome Assembly for Soft-Stem Bulrush (Schoenoplectus tabernaemontani) Confirms a Clade-Specific Whole-Genome Duplication in Cyperaceae.

Schoenoplectus tabernaemontani (C. C. Gmelin) Palla is a typical macrophyte in diverse wetland ecosystems. This species holds great potential in decontamination applications and carbon sequestration. Previous studies have shown that this species may have experienced recent polyploidization. This would make S. tabernaemontani a unique model to study the processes and consequences of whole-genome duplications in the context of the well-documented holocentric chromosomes and dysploidy events in Cyperaceae. However, the inference was not completely solid because it lacked homology information that is essential to ascertain polyploidy. We present here the first chromosome-level genome assembly for S. tabernaemontani. By combining Oxford Nanopore Technologies (ONT) long reads and Illumina short reads, plus chromatin conformation via the Hi-C method, we assembled a genome spanning 507.96 Mb, with 99.43% of Hi-C data accurately mapped to the assembly. The assembly contig N50 value was 3.62 Mb. The overall BUSCO score was 94.40%. About 68.94% of the genome was comprised of repetitive elements. A total of 36,994 protein-coding genes were predicted and annotated. Long terminal repeat retrotransposons accounted for ∼26.99% of the genome, surpassing the content observed in most sequenced Cyperid genomes. Our well-supported haploid assembly comprised 21 pseudochromosomes, each harboring putative holocentric centromeres. Our findings corroborated a karyotype of 2n = 2X = 42. We also confirmed a recent whole-genome duplication occurring after the divergence between Schoenoplecteae and Bolboschoeneae. Our genome assembly expands the scope of sequenced genomes within the Cyperaceae family, encompassing the fifth genus. It also provides research resources on Cyperid evolution and wetland conservation.

Posterior Eye Shape in Myopia.

Purpose: To explore prevalence and associated factors of abnormalities of the posterior eye shape in dependence of axial length. Design: Population-based study. Participants: Of the participants (n = 3468) of the Beijing Eye Study, we included all eyes with an axial length of ≥25 mm, and a randomized sample of eyes with an axial length of <25 mm. Methods: Using 30°-wide, serial horizontal, and fovea-centered radial, OCT images, we examined location and depth of the most posterior point of the retinal pigment epithelium/Bruch's membrane line (PP-RPE/BML). Main Outcome Measures: Prevalence and depth of an extrafoveal PP-RPE/BML. Results: The study included 366 eyes (314 individuals). On the radial OCT scans, the PP-RPE/BML was located in the foveola in 190 (51.9%) eyes, in 121 (33.1%) eyes in the 6 o'clock part of the vertical meridian (distance to foveola: 1.73 ± 0.70 mm), and in 54 (14.8%) eyes in the 12 o'clock part of the vertical meridian (fovea distance: 2.01 ± 0.66 mm). On the horizontal OCT scans, the PP-RPE/BML was located in the foveola in 304 (83.1%) eyes, between foveola and optic disc in 36 (9.8%) eyes (fovea distance: 1.59 ± 0.76 mm), and temporal to the foveola in 26 (7.1%) eyes (fovea distance: 1.20 ± 0.60 mm). Higher prevalence of an extrafoveal PP-RPE/BML correlated with longer axial length (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.28, 1.89), higher corneal astigmatism (OR: 1.78; 95% CI: 1.14, 2.79), and female sex (OR: 2.74; 95% CI: 1.30, 5.77). The curvature of the RPE/BML at the posterior pole was similar to the RPE/BML curvature outside of the posterior pole in 309 (84.4%) eyes, and it was steeper (i.e., smaller curvature radius) in 57 (15.6%) eyes. In these eyes, axial length was longer (24.41 ± 1.78 mm versus 27.74 ± 1.88 mm; P < 0.001). Conclusions: With longer axial length, the foveola is more often located outside of the geometrical posterior pole. It may be of importance for biometric axial length measurements. An extrafoveal location of the PP-RPE/BML may be due to an axial elongation-associated, meridionally asymmetric enlargement of Bruch's membrane in the fundus midperiphery. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Linking active rectal mucosa-attached microbiota to host immunity reveals its role in host-pathogenic STEC O157 interactions.

The rectal-anal junction (RAJ) is the major colonization site of Shiga toxin-producing Escherichia coli (STEC) O157 in beef cattle, leading to transmission of this foodborne pathogen from farms to food chains. To date, there is limited understanding regarding whether the mucosa-attached microbiome has a profound impact on host-STEC interactions. In this study, the active RAJ mucosa-attached microbiota and its potential role in host immunity-STEC commensal interactions were investigated using RAJ mucosal biopsies collected from calves orally challenged with two STEC O157 strains with or without functional stx2a (stx2a+ or stx2a-). The results revealed that shifts of microbial diversity, topology, and assembly patterns were subjected to stx2a production post-challenge and Paeniclostridium and Gallibacterium were the keystone taxa for both microbial interactions and assembly. Additional mucosal transcriptome profiling showed stx2a-dependent host immune responses (i.e. B- and T-cell signaling and antigen processing and presentation) post-challenge. Further integrated analysis revealed that mucosa-attached beneficial microbes (i.e. Provotella, Faecalibacterium, and Dorea) interacted with host immune genes pre-challenge to maintain host homeostasis; however, opportunistic pathogenic microbes (i.e. Paeniclostridium) could interact with host immune genes after the STEC O157 colonization and interactions were stx2a-dependent. Furthermore, predicted bacterial functions involved in pathogen (O157 and Paeniclostridium) colonization and metabolism were related to host immunity. These findings suggest that during pathogen colonization, host-microbe interactions could shift from beneficial to opportunistic pathogenic bacteria driven and be dependent on the production of particular virulence factors, highlighting the potential regulatory role of mucosa-attached microbiota in affecting pathogen-commensal host interactions in calves with STEC O157 infection.

Plateletcrit is predictive of clinical outcome and prognosis for early-stage breast cancer: A retrospective cohort study based on propensity score matching.

PURPOSE: Breast cancer (BC) is diagnosed as the most common cancer in women in 2022 according to the American Cancer Society. It is essential to detect early and treat early. Several studies have shown that some blood parameters have important predictive value for BC. In this study, we aim to explore whether some immune-associated blood parameters are relevant to disease-free survival (DFS) in early-stage BC. METHODS: A single-center, regression cohort study of 1490 patients with early-stage BC in Shanghai Cancer Center was conducted from January 2008 to December 2016. The patients were matched according to the ratio of 1:1 based on Propensity Score Matching (PSM). All patients who experienced disease progression were matched successfully. Thus, 58 pairs of subjects were obtained. Matched blood parameters were evaluated by paired samples t-test or Wilcoxon signed-rank test. Factors with statistical difference were further evaluated by stratified COX regression model. RESULTS: Univariate analysis showed differences in platelet-related parameters (PLT, PCT, and PLR) and NLR between the two matched groups. However, stratified COX regression analysis, which ruled out the confounding effects of multiple factors, found that only PCT had prognostic value in early BC patients at baseline and study endpoint. Meanwhile, platelet-related parameters (PLT, MPV) and NLR were different in the progressive group by self before and after comparison. However, the multiple-factor analysis showed that only the NLR had prognostic value. ROC curve analysis indicated that the best sensitivity (65.45%) and specificity (78.18%) were obtained when the baseline PCT was 0.225. The optimal sensitivity (70.91%) and specificity (65.45%) were obtained when the PCT of disease progression was 0.215. The Kaplan-Meier curve was used to calculate the DFS rate based on the critical values of the two groups. CONCLUSIONS: Some blood parameters have value to predict DFS in early-stage BC patients, especially platelet-associated parameters.

Outcomes with and without postmastectomy radiotherapy for pT3N0-1M0 breast cancer: An institutional experience.

AIM: The objective of this study is to comprehensively evaluate the therapeutic efficacy of postmastectomy radiotherapy (PMRT) in treating patients with pT3N0-1M0 breast cancer within the context of modern therapeutic strategies. METHODS: Clinical data from patients with pT3N0-1M0 breast cancer who underwent mastectomy from January 2005 to December 2018 at our institution were retrospectively analyzed. RESULTS: The study involved a total of 222 participants, with 112 individuals undergoing PMRT and 110 individuals not receiving it. The median follow-up duration was 77 months (range: 6-171 months). The entire cohort demonstrated 5-year disease-free survival (DFS) and overall survival (OS) rates of 85.1% and 91.0%, respectively, along with a locoregional recurrence (LRR) rate as low as 7.2%. The PMRT group showed significantly better 5-year DFS (90.2% vs. 80.0%, p = 0.02) and OS (95.5% vs. 86.4%, p = 0.012) rates, as well as a lower LRR rate (4.5% vs. 10.0%, p = 0.122), compared to the group without PMRT. Cox regression analysis confirmed the independent prognostic significance of PMRT for both DFS (p = 0.040) and OS (p = 0.047). Following propensity score matching (PSM), the analysis included 100 matched patients, revealing an improved prognosis for those who received PMRT (DFS: p = 0.067; OS: p = 0.043). CONCLUSIONS: Our study reveals favorable prognoses for pT3N0-1M0 breast cancer patients treated within contemporary therapeutic approaches. The pivotal role of PMRT in this context is evident. However, due to the retrospective design of our study and the relatively limited sample size, further investigation is imperative to validate and enhance these initial findings.

Prevalence, Features and Risk Factors of Macular Retinoschisis in High Myopic Population: the Beijing Eye Study 2011: Macular Retinoschisis in High Myopic Population.

PURPOSE: To investigate the prevalence, features and risk factors of macular retinoschisis (MRS) in highly myopic eyes and their morphological features in Chinese population. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: From Beijing Eye Study 2011, a total of 213 highly myopic eyes from 129 participants were included. METHODS: All participants underwent Spectral-domain optical coherence tomography with a macula cube scan of 30°â€¯× 30°centered in the fovea. MAIN OUTCOME MEASURES: High myopia was defined as a refractive error ≤-6 diopters or an axial length ≥ 26.0 mm. MRS presence and its subtypes were assessed based on location and affected retinal layers were evaluated. Prevalence, features and associated factors of MRS and its subtypes in highly myopic population were assessed. RESULTS: Out of 213 highly myopic eyes (129 participants), MRS was observed in 48 eyes, with a prevalence of 22.5% (95%CI: 16.9, 28.6%) per eye, or 36 participants with 27.9% (95% CI: 20.5, 35.7%) per subject. In addition to well-documented factors like older age and higher myopia, the prevalence of MRS was found to be related with a higher intraocular pressure (P=0.013, OR: 1.25; 95%CI: 1.05, 1.48), a thinner subfoveal choroidal thickness (P=0.006 OR: 0.86; 95%CI: 0.77, 0.96), a wider Gamma zone (P=0.003, OR: 1.99; 95%CI: 1.05, 3.11), the presence of glaucoma (P=0.010, OR: 3.37; 95%CI: 1.34, 8.48) and the presence of epiretinal membrane (P=0.023, OR: 3.13; 95%CI: 1.17, 8.36), after multivariate analysis. Eyes with advanced high myopia (P=0.021) and wider gamma zone (P=0.005) were more likely to develop foveal MRS. Eyes with glaucoma tended to have a higher prevalence of outer retinal MRS compared to inner retinal MRS (60.9% versus 36.0%), though the difference was not statistically significant (P=0.06). MRS located in the foveal region or affecting the outer retina was related with a significant worse best corrected visual acuity (BCVA), as compared to MRS that was perifoveally located or affected other regions (P<0.05). CONCLUSIONS: The prevalence of MRS was 27.9% among the elderly highly myopic population. MRS occurring in the foveal region or involving the outer retina demands increased vigilance due to its significant impact on BCVA. The findings contribute to a deeper understanding of MRS, offering insights into its mechanisms and vision prognosis.