Clinicopathological characteristics and prognostic factors in invasive micropapillary carcinoma of the breast.

Introduction: Invasive micropapillary carcinoma (IMPC) treatment only relies on the standard treatment of nonspecific invasive breast cancer (NSIBC), and it remains controversial whether the survival of patients improves. Therefore, this study aimed to analyze the clinicopathological features of IMPC and to investigate the factors affecting its prognosis. Material and methods: This retrospective cohort study included 104 IMPC patients who met the study's inclusion criteria out of a total of 4,532 patients with invasive breast cancer between January 2015 and December 2019. A contemporaneous cohort of 230 patients with non-specific invasive breast cancer (NSIBC) who underwent surgery was identified and matched using propensity scores. Results: The survival rate for patients with IMPC ranged from 1.12% to 7.03%. Statistically significant differences were observed in the proportion of endocrine treatment, lymphatic invasion, estrogen receptor (ER)-positive rate, molecular subtypes, molecular typing, and 5-year loco-regional recurrence-free survival (LRRFS) between the two cohorts (p < 0.05). The univariate analysis showed that T stage, N stage, lymphatic invasion, vascular invasion, ER-positive rate, and progesterone receptor (PR)-negative rate were all prognosis risk factors (p < 0.05) for IMPC. Furthermore, the multivariate analysis indicated that lymphatic invasion and N stage were independent prognostic factors (p < 0.05). Conclusions: The incidence of micropapillary IMPC, among other pathological subtypes, is steadily increasing. ER-positive and PR-positive rates, as well as luminal subtypes, are frequent, with a concurrent increase in the 5-year locoregional recurrence rate. It would be interesting to compare the effect following these therapeutic modifications in larger cohorts in future studies.

The Role of Ki-67 in HR+/HER2- Breast Cancer: A Real-World Study of 956 Patients.

Objective: This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;. Materials and Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone. Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P<0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P <0.001). Survival analysis was based on all patients for a median of 51 months (24-89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium. Conclusion: In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.

Left ventricular thrombosis caused cerebral embolism during venoarterial extracorporeal membrane oxygenation support: A case report.

BACKGROUND: Venoarterial (VA) extracorporeal membrane oxygenation (ECMO), an effective short-term circulatory support method for refractory cardiogenic shock, is widely applied. However, retrospective analyses have shown that VA-ECMO-assisted cases were associated with a relatively high mortality rate of approximately 60%. Embolization in important organs caused by complications of left ventricular thrombosis (LVT) during VA-ECMO is also an important reason. Although the incidence of LVT during VA-ECMO is not high, the consequences of embolization are disastrous. CASE SUMMARY: A 37-year-old female patient was admitted to hospital because of fever for 4 d and palpitations for 3 d. After excluding the diagnosis of coronary heart disease, we established a diagnosis of "clinically explosive myocarditis". The patient still had unstable hemodynamics after drug treatment supported by VA-ECMO, with heparin for anticoagulation. On day 4 of ECMO support, a left ventricular thrombus attached to the papillary muscle root of the mitral valve was found by transthoracic echocardiography. Left ventricular decompression was performed and ECMO was successfully removed, but the patient eventually died of multiple cerebral embolism. CONCLUSION: LVT with high mobility during VA-ECMO may cause embolism in important organs. Therefore, a "wait and see" strategy should be avoided.

GRA: Graph Representation Alignment for Semi-Supervised Action Recognition.

Graph convolutional networks (GCNs) have emerged as a powerful tool for action recognition, leveraging skeletal graphs to encapsulate human motion. Despite their efficacy, a significant challenge remains the dependency on huge labeled datasets. Acquiring such datasets is often prohibitive, and the frequent occurrence of incomplete skeleton data, typified by absent joints and frames, complicates the testing phase. To tackle these issues, we present graph representation alignment (GRA), a novel approach with two main contributions: 1) a self-training (ST) paradigm that substantially reduces the need for labeled data by generating high-quality pseudo-labels, ensuring model stability even with minimal labeled inputs and 2) a representation alignment (RA) technique that utilizes consistency regularization to effectively reduce the impact of missing data components. Our extensive evaluations on the NTU RGB+D and Northwestern-UCLA (N-UCLA) benchmarks demonstrate that GRA not only improves GCN performance in data-constrained environments but also retains impressive performance in the face of data incompleteness.

X-ray excited luminescent nanoparticles for deep photodynamic therapy.

Photodynamic therapy (PDT), as a non-invasive treatment, has received wide attention because of its high selectivity and low side effects. However, traditional PDT is influenced by the excitation light source and the light penetration depth is limited, which can only be used for superficial epidermal tumor treatment, and it is still a great challenge for deep tumor treatment. In recent years, X-ray excitation photodynamic therapy (X-PDT) using penetrating X-rays as an external excitation source and X-ray excited luminescent nanoparticles (XLNP) as an energy transfer medium to indirectly excite photosensitizer (PS) has solved the problem of insufficient penetration depth in tissues and become a research hotspot in the field of deep tumor treatment. In this review, the recent research progress of nanoparticles for efficient X-PDT, listing different types of XLNP and luminescence enhancement strategies. The loading method of PS is highlighted to achieve efficient energy transfer by regulating the intermolecular distance between both XLNP/PS. In addition, the water-soluble modification of XLNP surface is discussed and different hydrophilic modification methods are proposed to provide reference ideas for improving the dispersibility and biocompatibility of XLNP in aqueous solution. Finally, the therapeutic effects about X-PDT are discussed, and the current challenges and future perspectives for its clinical applications are presented.

Co-pyrolysis of dyeing sludge and pine sawdust in a fluidized bed: Characterization and analysis of pyrolytic products and investigation of synergetic effects.

Co-pyrolysis of dyeing sludge (DS) and pine sawdust (PS) was carried out in a fluidized bed pyrolyser. The results revealed that addition of PS increased the yields of condensate and gas, and dramatically improved pore structure of co-pyrolysis char, enhancing immobilization of the metals, nutrient and pollution elements. Catalysts (Na-ZSM-5 and HZSM-5) significantly reduced tar and coke, strengthened the integrity of pore structure. Yield of nitrogen-containing compounds declined sharply from 88.66% to 8.14% when 25% of PS was added. Addition of 50% PS promoted ring opening to generate chain compounds and abundant oxygenates (such as ketones, aldehydes and carboxylic acids) in pyrolysis oil (PO) at 650 °C. Correspondingly, yield of gaseous products was inhibited except CO2 and H2 when PS content was dominant. The catalysts greatly increased yield of gaseous products by enhancing primary and secondary cracking depending on different feedstocks and catalysts (e.g., DS over Na-ZSM-5 and PS over HZSM-5). The maximum energy efficiency (69.75%) was obtained at 650 °C when 75% PS was added.

WAKE-mediated modulation of cVA perception via a hierarchical neuro-endocrine axis in Drosophila male-male courtship behaviour.

The nervous and endocrine systems coordinate with each other to closely influence physiological and behavioural responses in animals. Here we show that WAKE (encoded by wide awake, also known as wake) modulates membrane levels of GABAA receptor Resistance to Dieldrin (Rdl), in insulin-producing cells of adult male Drosophila melanogaster. This results in changes to secretion of insulin-like peptides which is associated with changes in juvenile hormone biosynthesis in the corpus allatum, which in turn leads to a decrease in 20-hydroxyecdysone levels. A reduction in ecdysone signalling changes neural architecture and lowers the perception of the male-specific sex pheromone 11-cis-vaccenyl acetate by odorant receptor 67d olfactory neurons. These finding explain why WAKE-deficient in Drosophila elicits significant male-male courtship behaviour.

Refractory adult Coats disease treated with dexamethasone intravitreal implant: A case report.

INTRODUCTION: Coats disease is a sporadic, retinal vascular abnormality, causing blindness. Several interventional methods, including laser photocoagulation, have been proposed; however, the use of intravitreal dexamethasone in refractory Coats disease is not well described. PATIENT CONCERNS: A 38-year-old man presented with a painless reduction in visual acuity in his right eye, commencing 15 days prior to initial assessment. DIAGNOSIS: Clinical manifestations and multimodal imaging indicated Coats disease. INTERVENTIONS: Retinal laser photocoagulation was performed in the nonperfused areas, 15 months later, the exudative retinal detachment, and macular edema remained, the patient was then treated with an intravitreal slow-release dexamethasone implant. OUTCOMES: The exudative retinal detachment and macular edema had resolved, and the BCVA had also improved. CONCLUSION: Dexamethasone intravitreal implantation was effective in treating refractory Coats disease.

Luminescent and magnetic bifunctional coordination complex based on a chiral tartaric acid derivative and europium.

A new mononuclear europium complex incorporating the (+)-di-p-toluoyl-D-tartaric acid (D-H2DTTA) ligand, namely, catena-poly[tris{µ2-3-carboxy-2,3-bis[(4-methylphenyl)carbonyloxy]propanoato}tris(methanol)europium(III)], [Eu(C20H17O8)3(CH3OH)3]n, (I), has been synthesized and characterized by IR spectroscopy, elemental analysis, powder X-ray diffraction and single-crystal X-ray diffraction analysis. The structure analysis indicates that complex (I) crystallizes in the trigonal space group R3 and exhibits an infinite one-dimensional chain structure, in which the Eu3+ ion is surrounded by six O atoms from six D-HDTTA- ligands and three O atoms from three coordinated methanol molecules, thus forming a tricapped trigonal prism geometry. The D-H2DTTA ligand is partially deprotonated and adopts a µ1,6-coordination mode via two carboxylate groups to link adjacent Eu3+ ions, affording an infinite one-dimensional propeller-shaped coordination polymer chain along the c axis, with an Eu...Eu distance of 7.622 (1) Å. Moreover, C-H...π interactions lead to the formation of helical chains running along the c axis and the whole structure displays a snowflake pattern in the ab plane. The circular dichroism spectrum confirms the chirality of complex (I). The solid-state photoluminescence properties were also investigated at room temperature and (I) exhibits characteristic red emission bands derived from the Eu3+ ion (CIE 0.63, 0.32), with a reasonably long lifetime of 0.394 ms, indicating effective energy transfer from the ligand to the metal centre. In addition, a magnetic investigation reveals single-ion magnetic behaviour. The spin-orbit coupling parameter (λ) between the ground and excited states is fitted to be 360 (2) cm-1 through Zeeman perturbation. Therefore, complex (I) may be regarded as a chiral optical-magneto bifunctional material.

Analysis of the related risk factors of postoperative delirium in patients with Stanford type A aortic dissection / 天津医药

Objective To analyze the related risk factors of postoperative delirium(POD)in patients with Stanford type A aortic dissection, and to guide clinical practices. Methods The clinical data of 118 cases [81 males and 37 females, average age (55.0 ± 10.3) years] with Stanford type A aortic dissection in Tianjin Chest Hospital from January 2016 to December 2017 were analysed in this study. According to whether developed delirium after surgery, the patients were divided into POD group(n=56)and Non-POD group(n=62).The preoperative,perioperative,and postoperative clinical data were collected.The univariate and multivariate Logistic regression analysis was used to investigate the risk factors of POD in patients with the Stanford type A aortic dissection. Results Single factor analysis showed that the proportions of drinking and cerebrovascular history significantly increased,the proportions of early electrolyte disorder and hypoxemia significantly increased, the levels of granulocytes / lymphocytes, circulatory time and blood volume during operation increased significantly, and the duration from onset to operation was decreased, but fibrinogen level decreased significantly in POD group than those of Non-POD group (P < 0.05). Multivariate Logistic analysis indicated that the more intraoperative consumption of blood (OR=1.733, 95% CI:1.409-2.129) and early postoperative electrolyte disorder (OR=10.500, 95% CI:2.930-37.622)were independent risk factors of POD,while the higher level of preoperative fibrinogen(OR=0.157,95% CI:0.050-0.635) and longer time from onset to surgery (OR=0.871, 95% CI:0.808-0.943) were protective factors of POD in patients with Stanford type A aortic dissection.Conclusion The early identification of risk factors of POD,and the active intervention of POD have a positive significance to reduce the occurrence of POD.

miR-3646 promotes cell proliferation, migration, and invasion via regulating G2/M transition in human breast cancer cells.

MicroRNAs (miRNAs) are small non-coding RNAs that are often located in genomic breakpoint regions and play a critical role in regulating a variety of the cellular processes in human cancer. miR-3646 has been reported to take part in tumorigenic progression in breast and bladder cancer, but its potential functions and exact mechanistic roles in breast cancer are still unclear. The objective of this study was to investigate the role of miR-3646 in breast cancer growth and metastasis using both bioinformatic and experimental approaches. Before starting the bench work, we conducted a bioinformatic study to predict the target genes regulated by miR-3646 using a panel of different algorithms. The results showed that miR-3646 might regulate a large number of genes that are related to cell growth, proliferation, metabolis, transport, and apoptosis and some were cancer-related genes. We found that the expression level of miR-3646 was significantly upregulated in breast cancer cells and tissues compared with normal breast cells and no tumor tissues. Subsequently, the MTT and colony formation assay results showed that up-regulation of miR-3646 promoted the cell viability and proliferation. Our results also showed that down-regulation of miR-3646 arrested the cells in G2/M phase in MCF7 and MDA-MB-231 cells which was accompanied by the down-regulation of CDK1/CDC2 and cyclin B1 and upregulation of p21Waf1/Cip1, p27 Kip1, and p53, suggesting that down-regulation of miR-3646 induces G2/M arrest through activation of the p53/p21/CDC2/cyclin B1 pathway. In addition, overexpression of miR-3646 promoted migration and invasion of MCF7 and MDA-MB-231 cells. Taken together, miR-3646 is a potential oncogene in breast cancer and it may represent a new niomarker in the diagnosis and prediction of prognosis and therapeutic response.

Identification of 13 novel mutations including a retrotransposal insertion in SLC25A13 gene and frequency of 30 mutations found in patients with citrin deficiency.

Deficiency of citrin, liver-type mitochondrial aspartate-glutamate carrier, is an autosomal recessive disorder caused by mutations of the SLC25A13 gene on chromosome 7q21.3 and has two phenotypes: neonatal intrahepatic cholestatic hepatitis (NICCD) and adult-onset type II citrullinemia (CTLN2). So far, we have described 19 SLC25A13 mutations. Here, we report 13 novel SLC25A13 mutations (one insertion, two deletion, three splice site, two nonsense, and five missense) in patients with citrin deficiency from Japan, Israel, UK, and Czech Republic. Only R360X was detected in both Japanese and Caucasian. IVS16ins3kb identified in a Japanese CTLN2 family seems to be a retrotransposal insertion, as the inserted sequence (2,667-nt) showed an antisense strand of processed complementary DNA (cDNA) from a gene on chromosome 6 (C6orf68), and the repetitive sequence (17-nt) derived from SLC25A13 was found at both ends of the insert. All together, 30 different mutations found in 334 Japanese, 47 Chinese, 11 Korean, four Vietnamese and seven non-East Asian families have been summarized. In Japan, IVS16ins3kb was relatively frequent in 22 families, in addition to known mutations IVS11 + 1G > A, 851del4, IVS13 + 1G > A, and S225X in 189, 173, 48 and 30 families, respectively; 851del4 and IVS16ins3kb were found in all East Asian patients tested, suggesting that these mutations may have occurred very early in some area of East Asia.

[Progresses and perspectives in the study on citrin deficiency].

Citrin deficiency causes autosomal recessive disorders including adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The responsive gene of citrin deficiency, SLC25A13, locates on chromosome 7q21.3 and encodes citrin as a liver-type mitochondrial aspartate/glutamate carrier (AGC). The mutations on SLC25A13 will result in deficiency of citrin and CTLN2 or NICCD. Citrin deficiency was found at first in Japan. However, recently, some of cases were identified in China, Korea, Vietnam, Israel, Czech, United States and England, and racial differences of the SLC25A13 mutations were found, suggesting the patients with citrin deficiency maybe exist worldwide. In this article, authors reviewed the progresses in the study on citrin deficiency up to now and put forward authors' considerations for further research on it.

Fasting-induced reduction in locomotor activity and reduced response of orexin neurons in carnitine-deficient mice.

We found reduced locomotor activity (LA) under fasting in systemic carnitine-deficient juvenile visceral steatosis (jvs(-/-)) mice. When food was withdrawn at 8:00 a.m. (lights-off at 7:00 p.m., 12h/cycle), the nocturnal LA of jvs(-/-) mice was much less than the control (jvs(+/+) and jvs(+/-)) mice. LA recovered under carnitine or sucrose administration, but not under medium-chain triglyceride. In addition, fasted jvs(-/-) mice, without any energy supply, were activated by modafinil, a stimulator of the dopamine pathway. These results suggest that the reduced LA is not adequately explained by energy deficit. As the fasted jvs(-/-) mice showed lower body core temperature (BT), we examined the central nervous system regulating LA and BT. We found lower percentage of c-Fos positive orexin neurons in the lateral hypothalamus and reduced orexin-A concentration in the cerebrospinal fluid of fasted jvs(-/-) mice. Sleep analysis revealed that fasted jvs(-/-) mice had disruption of prolonged wakefulness, with a higher frequency of brief episodes of non-REM sleep during the dark period than fasted jvs(+/+) mice. These results strongly suggest that the reduced LA in fasted jvs(-/-) mice is related to the inhibition of orexin neuronal activity.

Progresses and perspectives in the study on citrin deficiency / 中华医学遗传学杂志

Citrin deficiency causes autosomal recessive disorders including adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD). The responsive gene of citrin deficiency, SLC25A13, locates on chromosome 7q21.3 and encodes citrin as a liver-type mitochondrial aspartate/glutamate carrier (AGC). The mutations on SLC25A13 will result in deficiency of citrin and CTLN2 or NICCD. Citrin deficiency was found at first in Japan. However, recently, some of cases were identified in China, Korea, Vietnam, Israel, Czech, United States and England, and racial differences of the SLC25A13 mutations were found, suggesting the patients with citrin deficiency maybe exist worldwide. In this article, authors reviewed the progresses in the study on citrin deficiency up to now and put forward authors' considerations for further research on it.

Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.

Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier (AGC), encoded by the SLC25A13 gene on chromosome 7q21.3, causes autosomal recessive disorders: adult-onset type II citrullinemia (CTLN2) and neonatal hepatitis associated with intrahepatic cholestasis (NICCD). So far, we have described 12 SLC25A13 mutations: 11 were from Japan and one from Israel. Three mutations found in Chinese and Vietnamese patients were the same as those in Japanese patients. In the present study, we identified a novel mutation IVS6+1G>C in a Japanese CTLN2 patient and widely screened 12 SLC25A13 mutations found in Japanese patients in control individuals from East Asia to confirm our preliminary results that the carrier frequency was high in Asian populations. Mutations 851-854del and 1638-1660dup were found in all Asian countries tested, and 851-854del associated with 290-haplotype in microsatellite marker D7S1812 was especially frequent. Other mutations frequently detected were IVS11+1G>A in Japanese and Korean, S225X in Japanese, and IVS6+5G>A in Chinese populations. We found a remarkable difference in carrier rates in China (including Taiwan) between north (1/940) and south (1/48) of the Yangtze River. We detected many carriers in Chinese (64/4169 = 1/65), Japanese (20/1372 = 1/69) and Korean (22/2455 = 1/112) populations, suggesting that over 80,000 East Asians are homozygotes with two mutated SLC25A13 alleles.

Clinical heterogeneity of neonatal intrahepatic cholestasis caused by citrin deficiency: case reports from 16 patients.

A deficiency of citrin, which is encoded by the SLC25A13 gene, causes both adult-onset type II citrullinemia (CTLN2) and neonatal intrahepatic cholestasis (NICCD). We analyzed 16 patients with NICCD to clarify the clinical features of the disease. Severe intrahepatic cholestasis with fatty liver was the most common symptom, but the accompanying clinical features were variable, namely; suspected cases of neonatal hepatitis or biliary atresia, positive results from newborn screening, tyrosinemia, failure to thrive, hemolytic anemia, bleeding tendencies and ketotic hypoglycemia. Laboratory data showed elevated serum bile acid levels, hypoproteinemia, low levels of vitamin K-dependent coagulation factors, and hypergalactosemia. Hypercitrullinemia was detected in 11 out of 15 patients examined. Most of the patients were given a lactose-free and/or medium chain triglycerides-enriched formula and lipid-soluble vitamins. The prognosis of the 16 patients is going fairy well at present, but we should observe these patients carefully to see if they manifest any symptom of CTLN2 in the future.

Adult-onset type II citrullinemia and idiopathic neonatal hepatitis caused by citrin deficiency: involvement of the aspartate glutamate carrier for urea synthesis and maintenance of the urea cycle.

Citrin is a mitochondrial aspartate glutamate carrier primarily expressed in the liver, heart, and kidney. We found that adult-onset type II citrullinemia is caused by mutations in the SLC25A13 gene that encodes for citrin. In this report, we describe the frequency of SLC25A13 mutations, the roles of citrin as a member of the urea cycle and as a member of the malate-aspartate shuttle, the relationship between its functions and symptoms of citrin deficiency, and therapeutic issues.