Pathological diagnosis is the gold standard for confirming breast cancer. Traditional manual pathological diagnosis methods for breast cancer are time-consuming, labor-intensive, highly subjective, and exhibit poor diagnostic consistency. In recent years, artificial intelligence (AI) technology has rapidly advanced and is progressively being applied clinically as a promising early diagnostic tool. However, many existing AI models lack interpretability, which limits the trustworthiness of their clinical application. Khater et al, by combining a high-precision machine learning model with an explainable AI model, achieved highly accurate breast tumor diagnosis and provided explanations for key biological and pathological features influencing the diagnostic results. This points the way for the future application and development of AI in medical diagnosis and treatment. The article interprets the main content of that study, and analyzes the advantages and limitations of AI in medical diagnosis and treatment, with the aim of promoting its better application in clinical practice.

Breast cancer is one of the most common malignant tumors in women, and its treatment and management strategies are crucial for improving patients’ prognosis and quality of life. Early breast cancer refers to lesions confined to the breast and regional lymph nodes (N1 stage) without distant metastasis. Thanks to the improvement of screening techniques, the detection rate of early breast cancer has increased. The “early diagnosis and early treatment” model has led to a decrease in breast cancer mortality, especially among young women. The 2024 European Society for Medical Oncology (ESMO) clinical practice guideline for the diagnosis, treatment, and follow-up of early breast cancer aims to provide comprehensive and standardized recommendations for the diagnosis and treatment of early breast cancer, helping clinicians make optimal decisions. This article interprets the main content of the guideline in order to provide references and assistance for the current clinical diagnosis and treatment of early breast cancer in China.

OBJECTIVE To optimize the freeze-drying process for sheep placenta slices. METHODS An orthogonal test design was used with pre-freezing time， drying time and drying temperature as indicators to screen for the optimal freeze-drying process for sheep placenta slices. The peptide content， ethanol-soluble extract content， and freeze-drying rate of sheep placenta were used as indicators，the analytic hierarchy process-criteria importance through intercriteria correlation （AHP-CRITIC） method was employed to determine the weight of each indicator and calculate the comprehensive score， which was verified using the technique for order of preference by similarity to ideal solution （TOPSIS） model. RESULTS The optimal preparation process was found to be the pre-freezing time of 2 hours， the drying time of 16 hours， and the drying temperature of 30 °C. The average values of peptide content， ethanol-soluble extract content， and freeze-drying rate for three batches of samples were 5.883 mg/mL， 27.1%， and 95.77%， respectively； the comprehensive scores of three batches were 96.42， 99.18 and 99.58， with RSD of 1.75%. CONCLUSIONS This study successfully optimized the freeze-drying process for sheep placenta slices， which can provide a reference for the quality standard setting and industrial production of this type of slice.

Objective:To prepare hydroxyapatite(HA)coating on polyether ether ketone(PEEK)surface by magnetron sputtering technique and to study its biosafety.Methods:Sulfonated PEEK was used to increase the binding area and HA coating was constructed on it using magnetron sputtering technology.SEM and energy dispersive spectroscopy(EDAX)were used to detect the construction effect.Cell adhesion assay,cytoskeletal fluorescence staining and SEM validation were used to assess cytologrcal safety.In vivo safety tests were conducted in SD rats and golden hamsters.Results:HA coating with gradient morphology was successfully constructed on the PEEK surface using above technique.The coating promoted cell adhesion,extension and proliferation.No systemic toxicity and no sig-nificant influence in HE staining of the main infernal organs samples were observed.The coating alleviated the oral mucosal irritation caused by simple sulfonation to a certain extent.Conclusion:HA coating can be prepared stably with magnetron sputtering technology and can meet the biosafety needs for clinical applications.

Objective To compare cortical inhibition(CI)function between patients with schizophrenia and depression,and to explore the correlation between CI function and clinical symptoms.Methods A total of 35 first episode schizophrenia(FES)patients,41 depression patients(21 with first episode depression,20 with recurrent depression),and 35 healthy controls(HC)were recruited.The positive and negative syndrome scale(PANSS)was used to assess symptoms in FES patients,while the 17-item Hamilton depression scale(HAMD-17)and Hamilton anxiety scale(HAMA)were used to assess symptoms in depression patients.All participants'cortical inhibition and excitation measures were examined using single or paired pulses transcranial magnetic stimulation.Analysis of covariance/generalized linear model was employed to compare cortical inhibition and excitation measures among groups including age,gender,and medication status as covariates.The correlations between cortical inhibition and excitation measures and clinical symptoms were analyzed.Results The cortical silent period(CSP)in FES group was longer than that in control group and depression group[(92.08±35.43)ms vs.(70.27±22.12)ms vs.(70.81±29.29)ms,P<0.05].Depression group was further divided into first episode depression(FED)and recurrent depression(RD)subgroups.The short-interval cortical inhibition(SICI)was weaker in FED group than in the RD group and the control group(0.76±0.44 vs.0.43±0.32 vs.0.45±0.20,P<0.05).In FED group,CSP was negatively correlated with the general symptom score of PANSS(r=-0.544,P<0.001),and SICI was negatively correlated with the negative symptom score of PANSS(r=-0.501,P=0.005).In the FED group,SICI was positively correlated with HAMD-17 score(r=0.605,P=0.028).Conclusion Both FES patients and FED patients exhibit abnormal CI.There are distinct characteristics between FES and FED.FES patients exhibit prolonged CSP,while FED patients exhibit decreased SICI.The abnormal CI in FES and FED are correlated with their clinical symptoms.

Glutamate receptor-like (GLR) is an important class of Ca²⁺ channel proteins, playing important roles in plant growth and development as well as in response to biotic and abiotic stresses. In this paper, we performed genome-wide identification of banana GLR gene family based on banana genomic data. Moreover, we analyzed the basic physicochemical properties, gene structure, conserved motifs, promoter cis-acting elements, evolutionary relationships, and used real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) to verify the expression patterns of some GLR family members under low temperature of 4 ℃ and different hormone treatments. The results showed that there were 19 MaGLR family members in Musa acuminata, 16 MbGLR family members in Musa balbisiana and 14 MiGLR family members in Musa itinerans. Most of the members were stable proteins and had signal peptides, all of them had 3-6 transmembrane structures. Prediction of subcellular localization indicated that all of them were localized on the plasma membrane and irregularly distributed on the chromosome. Phylogenetic analysis revealed that banana GLRs could be divided into 3 subclades. The results of promoter cis-acting elements and transcription factor binding site prediction showed that there were multiple hormone- and stress-related response elements and 18 TFBS in banana GLR. RT-qPCR analysis showed that MaGLR1.1 and MaGLR3.5 responded positively to low temperature stress and were significantly expressed in abscisic acid/methyl jasmonate treatments. In conclusion, the results of this study suggest that GLR, a highly conserved family of ion channels, may play an important role in the growth and development process and stress resistance of banana.
Musa/metabolism* ; Phylogeny ; Abscisic Acid/metabolism* ; Temperature ; Stress, Physiological/genetics* ; Hormones/metabolism* ; Gene Expression Regulation, Plant ; Plant Proteins/metabolism* ; Gene Expression Profiling

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease(5x FAD)and wild type mice at 2-,12-,and 24-month of age,we found an increased percentage of microglia in aging and Alzheimer's disease(AD)mice.Blood brain barrier injury may also have contributed to this increase.Immune regulation by microglia plays a major role in the progression of aging and AD,according to the functions of 41 intersecting differentially expressed genes in microglia.Signaling crosstalk between C-C motif chemokine ligand(CCL)and major histocompatibility complex-1 bridges intercellular communi-cation in the hippocampus during aging and AD.The amyloid precursor protein(APP)and colony stimulating factor(CSF)signals drive 5x FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus.Microglia are involved in the progression of aging and AD can be divided into 10 functional types.The strength of the interaction among microglial subtypes weakened with aging,and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.

Objective:To investigate the mechanism of levosimendan on acute kidney injury after cardiopulmonary resuscitation (CPR) in rats.Methods:Twenty-five healthy adult male SD rats were randomly divided into three groups: control group ( n=5), levosimendan group ( n=10) and experimental group ( n=10). A cardiac arrest-cardiopulmonary resuscitation model was established using smothering method in the experimental group and levosimendan group. The levosimendan group was treated with levosimandan during and after resuscitation, while the experimental group was given equivalent volume of saline solution during and after resuscitation, and the control group was only given equivalent volume of saline without performance of CPR. The rats in the three groups were sacrificed at 6 h after resuscitation. The serum and kidney tissue samples were collected. Serum biochemical indicators [serum creatinine (Scr), blood urea nitrogen (Bun), interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α)] were measured. HE staining and Paller score were used to identify the degree of kidney damage. Apoptosis was estimated by TUNEL staining. Western blot was used to detect the expression levels of phosphorylation of extracellular regulated protein kinases (p-ERK). One-way analysis of variance was used to compare the mean values of normally distributed measurement data between groups. Comparisons between groups were performed using the least significant difference t-test. Results:Scr (85.02±1.31) μmol/L, Bun (7.36±0.13) mmol/L, Paller score (7.3±0.2), IL-1β (302.20±17.35) pg/mL, IL-6 (564.60±23.24) pg/mL and TNF-α (1346±83.73) pg/mL in the experimental group were significantly higher than those of the control group [(15.94±0.96) μmol/L, (2.95±0.18) mmol/L, (0.7±0.2), (7.27±0.44) pg/mL, (51.30±2.87) pg/mL, and (10.39±0.52) pg/mL] (all P<0.01). Compared with the experimental group, Scr (63.88±2.01) μmol/L, Bun (5.45±0.47) mmol/L, paller score (4.8±0.2), IL-1β (78.61±3.66) pg/mL, IL-6 (297.90±13.64) pg/mL and TNF-α (276.2±20.18) pg/mL were significantly decreased in the levosimendan group (all P<0.01). TUNEL staining showed that levosimendan could improve the apoptosis of renal cells ( P<0.01). The expression of p-ERK protein in the levosimendan group was significantly higher than that in the experimental group ( P<0.01). Conclusions:Lovosimendan could attenuate acute kidney injury following cardiac arrest and cardiopulmonary resuscitation via suppression apoptosis. The mechanism of levosimendan protective effect might be associated with activation of ERK signaling pathway.

Objective:To investigate the effect of Asarinin on the survival time of transplanted heart after allogeneic heterotopic heart transplantation and to further verify the anti-immune rejection effect of Asarinin in spleen and peripheral blood.Methods:Using 64 Wistar rats as donors, 64 SD rats as recipients to establish the allogeneic heterotopic heart transplantation model in rats.After successful transplantation, 64 rats were use simple randomization divided into control group, cyclosporine A(CsA) group, Asarinin group and half CsA + half Asarinin group with 16 rats in each group.CsA group was given 5 mg/kg by gavage; Asarinin group was given 25 mg/kg; half dose group was given CsA 2.5 mg/kg+ Asarinin 12.5 mg/kg and the control group was given the same volume of normal saline by gavage.After administration for 1 week, half of them were used to observe the survival time.The other half of the rats were fully anesthetized with chloral hydrate, spleen and peripheral blood were taken.Half of the spleen was taken to observe the slices under the microscope.The other half of spleen was used RT-PCR to detect the relative expression of IFN-γ and IL-4.The expression of co-stimulatory molecules CD80, CD86 and CD40 in peripheral blood were detected by flow cytometry.Results:Survival time of transplanted heart was control group (8.4±0.9), CsA group (30.5±8.3), Asarinin group (16.5±4.3) and half-dose group (26.1±5.2) days.Compared with control group, survival time of heart transplantation became prolonged in all groups and the difference was statistically significant ( P<0.05). HE staining of splenic tissue showed that, as compared with control group, the injury of each group was alleviated.The relative expression of IFN-γ in spleen was control group (1.055±0.083), CsA group (0.396±0.038), Asarinin group (0.833±0.094) and half-dose group (0.862±0.104). The last three groups were lower than control group and the difference was statistically significant ( P<0.05). The relative expression of IL-4 in spleen was control group (1.429±0.234), CsA group (3.808±0.729), Asarinin group (2.209±0.306) and half-dose group (2.323±0.321). The last three groups all spiked as compared with control group and the difference was statistically significant ( P<0.05). The expressions of CD80, CD86 and CD40 in peripheral blood were control group (98.21±0.54), (85.78±0.89) and (96.36±0.66), CsA group (89.26±0.36), (56.86±2.32) and (88.11±1.61), Asarinin group (94.19±0.47), (79.01±1.12) and (87.86±1.67) and half-dose group (94.87±0.74), (80.81±0.98) and (89.71±0.97) respectively.The last three groups were lower than control group and the difference was statistically significant ( P<0.05). Conclusions:Asarinin can prolong the survival time of transplanted heart after allogeneic heterotopic heart transplantation in rats, inhibit the immune injury of spleen after allogeneic heterotopic heart transplantation in rats, decrease IFN-γ in spleen, increase IL-4 in spleen and inhibit the expression of peripheral blood costimulatory molecules CD80, CD86 and CD40.

OBJECTIVE: To explore the genetic basis of three families with recurrence of non-immune hydrops fetalis (NIHF) but negative result by copy number variation sequencing (CNV-seq). METHODS: Amniotic fluid sample and/or abortive tissues of the fetuses were collected and subjected to CNV-seq analysis. Peripheral blood samples of the parents were also taken for trio whole exome sequencing (trio WES). RESULTS: Fetus 1 was found to harbor heterozygous c.976G>T(p.Glu326*) variant of the SOX18 gene in addition with compound heterozygous variants c.844C>T(p.Arg282Trp) and c.9472+1G>A of the RYR1 gene. The three variants were all inherited from its parents and have been associated with the etiology of NIHF. Based on the American College of Medical Genetics and Genomics (ACMG) standards and guidelines, the c.976G>T variant of SOX18 gene and c.9472+1G>A of RYR1 gene were predicted to be pathogenic (PVS1+PM2+PP3+PP4, PVS1+PM2+PP3), and c.844C>T variant of RYR1 gene to be likely pathogenic (PM1+PM2+PP3). Fetus 2 was found to harbor compound heterozygous variants c.6682C>T(p.Gln2228*) and c.4373_4383del(p.Val1458Alafs*63) of the PIEZO1 gene. Both variants were also inherited from its parents and are associated with the etiology of NIHF. Based on ACMG standards and guidelines, both c.6682C>T and c.4373_4383del variants of PIEZO1 gene were predicted to be pathogenic (PVS1+PM2+PP4, PVS1+PM2). Fetus 3 was found to harbor compound heterozygous variants of the TTN gene c.29860G>C(p.Asp9954His) and c.21107A>T(p.Asp7036Val), which were respectively inherited from its parents. Both variants have been strongly associated with the phenotype, though the connection between the etiology of NIHF and variants of the TTN gene remains elusive. Based on ACMG standards and guidelines, the c.29860G>C and c.21107A>T variants of TTN gene were predicted to be likely pathogenic (PM1+PM2+PP3). CONCLUSION Trio WES can improve the diagnosis rate of NIHF with a negative result by CNV-seq. Considering the urgency of prenatal diagnosis, CNV-seq and trio WES should be carried out at the same time for fetuses with NIHF.
DNA Copy Number Variations ; Female ; Genomics ; Heterozygote ; Humans ; Hydrops Fetalis/genetics* ; Ion Channels ; Pregnancy ; SOXF Transcription Factors ; United States ; Whole Exome Sequencing