Deep Learning Based on Computed Tomography Predicts Response to Chemoimmunotherapy in Lung Squamous Cell Carcinoma.

Non-small-cell lung carcinoma (NSCLC) often carries a dire prognosis. The advent of neoadjuvant chemoimmunotherapy (NCI) has become a promising approach in NSCLC treatment, making the identification of reliable biomarkers for major pathological response (MPR) crucial. This study aimed to devise a deep learning (DL) model to estimate the MPR to NCI in lung squamous cell carcinoma (LUSC) patients and uncover its biological mechanism. We enrolled a cohort of 309 LUSC patients from various medical institutions. A ResNet50 model, trained on contrast-enhanced computed tomography images, was developed, and validated to predict MPR. We examined somatic mutations, genomic data, tumor-infiltrating immune cells, and intra-tumor microorganisms. Post-treatment, 149 (48.22%) patients exhibited MPR. The DL model demonstrated excellent predictive accuracy, evidenced by an area under the receiver operating characteristic curve (AUC) of 0.95 (95% CI: 0.98-1.00) and 0.90 (95% CI: 0.81-0.98) in the first and second validation sets, respectively. Multivariate logistic regression analysis identified the DL model score (low vs. high) as an independent predictor of MPR. The prediction of MPR (P-MPR) correlated with mutations in four genes, as well as gene ontology and pathways tied to immune response and antigen processing and presentation. Analysis also highlighted diversity in immune cells within the tumor microenvironment and in peripheral blood. Moreover, the presence of four distinct bacteria varied among intra-tumor microorganisms. Our DL model proved highly effective in predicting MPR in LUSC patients undergoing NCI, significantly advancing our understanding of the biological mechanisms involved.

Probiotics improves abnormal behavior and hippocampal injury in pregnant-stressed offspring rats. / ç›Šç”ŸèŒæ”¹å–„å­•æœŸåº”æ¿€å­ä»£å¤§é¼ å¼‚å¸¸è¡Œä¸ºå’Œæµ·é©¬æŸä¼¤.

OBJECTIVES: During pregnancy, pregnant women are prone to stress reactions due to external stimuli, affecting their own health and fetal development. At present, there is no good treatment for the stress reactions from pregnant women during pregnancy. This study aims to explore the effect of probiotics on abnormal behavior and hippocampal injury in pregnant stressed offspring. METHODS: SD pregnant rats were divided into a control group, a stress group, and a probiotics group, with 6 rats in each group. The control group was untreated; the stress group was given restraint stress on the 15th-20th day of pregnancy; the probiotics group was given both bifidobacterium trisporus capsules and restraint stress on the 15th-20th day of pregnancy, and the offspring continued to be fed with probiotics until 60 days after birth (P60). The offspring rats completed behavioral tests such as the open field test, the elevated plus maze test, the new object recognition test, and the barnes maze test at 60-70 d postnatally. Nissl's staining was used to reflect the injury of hippocampal neurons; immunohistochemical staining was used to detect the expression of microglia marker ionized calcium binding adapter molecule 1 (IBA-1) which can reflect microglia activation; ELISA was used to detect the content of plasma TNF-α and IL-1ß; Western blotting was used to detect the expression of Bax, Bcl-2, and caspase-3. RESULTS: The retention time of offspring rats in the stress group in the central area of the open field was significantly less than that in the control group (P<0.01), and the retention time of offspring rats in the probiotic group in the central area of the open field was significantly more than that in the stress group (P<0.05). The offspring rats in the stress group stayed in the open arm for a shorter time than the control group (P<0.05) and entered the open arm less often than the control group (P<0.01); the offspring rats in the probiotic group stayed in the open arm for a longer time than the stress group and entered the open arm more often than the stress group (both P<0.05). The discrimination ratio for new to old objects in the offspring rats of the stress group was significantly lower than that of the control group (P<0.01), and the discrimination ratio for new to old objects in the offspring rats of the probiotic group was significantly higher than that of the stress group (P<0.05). The offspring rats in the stress group made significantly more mistakes than the control group (P<0.05), and the offspring rats in the probiotic group made significantly fewer mistakes than the stress group (P<0.05). Compared with the control group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly reduced in the offspring rats of the stress group (all P<0.001), the number of activated microglia in DG area of hippocampus was significantly increased (P<0.01), the contents of TNF-α and IL-1ß in peripheral blood were significantly increased (P<0.05 or P<0.01), the protein expression level of Bcl-2 was significantly down-regulated, and the protein expression levels of Bax and caspase-3 were significantly up-regulated (all P<0.001). Compared with the stress group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly increased in the probiotic group offspring rats (P<0.001, P<0.01, P<0.05), the number of activated microglia in the DG area of hippocampus was significantly reduced (P<0.05), and the TNF-α and IL-1ß levels in peripheral blood were significantly decreased (both P<0.05), the protein expression level of Bcl-2 was significantly up-regulated, and the protein expression levels of Bax and caspase-3 were significantly down-regulated (all P<0.001). CONCLUSIONS: Probiotic intervention partially ameliorated anxiety and cognitive impairment in rats offspring of pregnancy stress, and the mechanism may be related to increasing the number of neurons, inhibiting the activation of hippocampal microglia, and reducing inflammation and apoptosis.

HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.

Human immunodeficiency virus (HIV)-infected people's livelihoods are gradually being prolonged with the use of combined antiretroviral therapy (ART). Conversely, despite viral suppression by ART, the symptoms of HIV-associated neurocognitive disorder (HAND) endure. HAND persists because ART cannot really permanently confiscate the virus from the body. HAND encompasses a variety of conditions based on clinical presentation and severity level, comprising asymptomatic neurocognitive impairment, moderate neurocognitive disorder, and HIV-associated dementia. During the early stages of HIV infection, inflammation compromises the blood-brain barrier, allowing toxic virus, infected monocytes, macrophages, T-lymphocytes, and cellular products from the bloodstream to enter the brain and eventually the entire central nervous system. Since there are no resident T-lymphocytes in the brain, the virus will live for decades in macrophages and astrocytes, establishing a reservoir of infection. The HIV proteins then inflame neurons both directly and indirectly. The purpose of this review is to provide a synopsis of the effects of these proteins on the central nervous system and conceptualize avenues to be considered in mitigating HAND. We used bioinformatics repositories extensively to simulate the transcription factors that bind to the promoter of the HIV-1 protein and possibly could be used as a target to circumvent HIV-associated neurocognitive disorders. In the same vein, a protein-protein interaction complex was also deduced from a Search Tool for the Retrieval of Interacting Genes. In conclusion, this provides an alternative strategy that could be used to avert HAND.

Gene diagnosis for nine Chinese patients with DMD/BMD by multiplex ligation-dependent probe amplification and prenatal diagnosis for one of them.

This study aims to perform gene diagnosis for nine patients with Duchenne/Becker muscular dystrophy (DMD/BMD) and their parents with multiplex ligation-dependent probe amplification (MLPA), and to carry out prenatal gene diagnosis for one of them. Genomic DNA of the peripheral blood and fetal amniotic fluid cell was extracted from the pedigrees' members with DMD/BMD. Gene diagnosis was performed for theses pedigrees' members using a SALSA KIT. Short tandem repeats (STR) genotyping and X-linkage analysis were performed for the pedigree members of the fetus, which was used in the prenatal diagnosis. MLPA analysis results show that five of nine patients (DMD-1, DMD-2, DMD-4, DMD-8, and DMD-9) with DMD/BMD were found to have several hemizygous exon deletions in the dystrophin gene. The other patients and the fetus did not have any hemizygous deletion or duplication of any exons. The genomic DNA of the fetus was not contaminated by his mother's DNA as identified by STR genotyping. In addition, X-linkage analysis results show that the only X chromosome of the fetus comes from one of his mother's normal X chromosomes. Combined with STR genotyping and X-linkage analysis, MLPA is a convenient, highly effective and reliable gene diagnosis technique for congenital genetic disease.

Successful boosting of a DNA measles immunization with an oral plant-derived measles virus vaccine.

Despite eradication attempts, measles remains a global health concern. Here we report results that demonstrate that a single-dose DNA immunization followed by multiple boosters, delivered orally as a plant-derived vaccine, can induce significantly greater quantities of measles virus-neutralizing antibodies than immunization with either DNA or plant-derived vaccines alone. This represents the first demonstration of an enhanced immune response to a prime-boost vaccination strategy combining a DNA vaccine with edible plant technology.