Background and objective Small cell lung cancer(SCLC)is known as recalcitrant cancer with high malignancy and heterogeneity.Immunotherapy has changed the treatment pattern of extensive-disease SCLC(ED-SCLC),but the beneficiary population is limited.Therefore,exploring new therapeutic strategies is an urgent clinical problem to be solved for SCLC.SCLC is characterized by highly active glycolytic metabolism and pyruvate kinase Ml(PKM1)is one of the isozymes of PK,an important rate-limiting enzyme in glycolysis pathway.Previous studies have shown that PKM1 is related to autophagy and drug sensitivity,however,how PKM1 regulates drug sensitivity in SCLC and its mechanism remain unclear.The aim of this study was to investigate the biological functions of PKM1 in SCLC,including its effects on proliferation,migra-tion,autophagy,drug sensitivity,and expression of neuroendocrine(NE)-related markers in SCLC.Methods Western blot was used to detect the expression level of PKM1 in SCLC cells.PKM1 gene-overexpressed SCLC cell lines were constructed by stable lentivirus transfection.Proliferation of cells and drug sensitivity were detected by MTT,and migration ability of cells was determined by Transwell.The level of autophagy was detected by flow cytometry.Western blot was used to determine the expression levels of NE-related proteins.Results PKM1 was differentially expressed among various SCLC cell lines,and was lower in H1092 cells(P＜0.01).Compared with the control group,there was no significant difference in proliferation level of PKM1 overexpressing H1092 cell,but the migration ability was significantly increased(P＜0.001),the drug sensitivity was re-duced,and the level of autophagy was inhibited(P＜0.001).Additionally,overexpression of PKM1 could upregulate the expres-sion of non-neuroendocrine(non-NE)-related proteins(P＜0.01)and decrease the expression of NE-related proteins(P＜0.01).Conclusion PKM1 was differentially expressed in SCLC cell lines,and high expression of PKM1 did not affect the prolifera-tion,but affected the migration of SCLC cells.PKM1 might affect drug sensitivity by inhibiting autophagy and regulating the expression of NE markers.These results provide a theoretical basis for exploring the role of PKM1 in SCLC.

Purpose: Prostate cancer (PCa) is an epithelial malignancy that originates in the prostate gland and is generally categorized into low, intermediate, and high-risk groups. The primary diagnostic indicator for PCa is the measurement of serum prostate-specific antigen (PSA) values. However, reliance on PSA levels can result in false positives, leading to unnecessary biopsies and an increased risk of invasive injuries. Therefore, it is imperative to develop an efficient and accurate method for PCa risk stratification. Many recent studies on PCa risk stratification based on clinical data have employed a binary classification, distinguishing between low to intermediate and high risk. In this paper, we propose a novel machine learning (ML) approach utilizing a stacking learning strategy for predicting the tripartite risk stratification of PCa. Methods: Clinical records, featuring attributes selected using the lasso method, were utilized with 5 ML classifiers. The outputs of these classifiers underwent transformation by various nonlinear transformers and were then concatenated with the lasso-selected features, resulting in a set of new features. A stacking learning strategy, integrating different ML classifiers, was developed based on these new features. Results: Our proposed approach demonstrated superior performance, achieving an accuracy of 0.83 and an area under the receiver operating characteristic curve value of 0.88 in a dataset comprising 197 PCa patients with 42 clinical characteristics. Conclusions This study aimed to improve clinicians’ ability to rapidly assess PCa risk stratification while reducing the burden on patients. This was achieved by using artificial intelligence-related technologies as an auxiliary method for diagnosing PCa.

OBJECTIVE: To investigate the effects of fecal microbiota transplantation (FMT) on intestinal microbiome and organism in patients with severe pneumonia during the convalescence period. METHODS: A prospective non-randomized controlled study was conducted. From December 2021 to May 2022, patients with severe pneumonia during the convalescence period who received FMT (FMT group) and patients with severe pneumonia during the convalescence period who did not receive FMT (non-FMT group) admitted to the First Affiliated Hospital of Guangzhou Medical University were enrolled. The differences of clinical indicators, gastrointestinal function and fecal traits between the two groups were compared 1 day before and 10 days after enrollment. The 16S rDNA gene sequencing technology was used to analyze the changes of intestinal flora diversity and different species in patients with FMT before and after enrollment, and metabolic pathways were analyzed and predicted by Kyoto Encyclopedia of Genes and Genomes database (KEGG). Pearson correlation method was used to analyze the correlation between intestinal flora and clinical indicators in FMT group. RESULTS: The level of triacylglycerol (TG) in FMT group was significantly decreased at 10 days after enrollment compared with before enrollment [mmol/L: 0.94 (0.71, 1.40) vs. 1.47 (0.78, 1.86), P < 0.05]. The level of high-density lipoprotein cholesterol (HDL-C) in non-FMT group was significantly decreased at 10 days after enrollment compared with before enrollment (mmol/L: 0.68±0.27 vs. 0.80±0.31, P < 0.05). There were no significant differences in other clinical indexes, gastrointestinal function or fecal character scores between the two groups. Diversity analysis showed that the α diversity indexes of intestinal flora in FMT group at 10 days after enrollment were significantly higher than those in non-FMT group, and β diversity was also significantly different from that in non-FMT group. Differential species analysis showed that the relative abundance of Proteobacteria at the level of intestinal flora in FMT group at 10 days after enrollment was significantly lower than that in non-FMT group [8.554% (5.977%, 12.159%) vs. 19.285% (8.054%, 33.207%), P < 0.05], while the relative abundance of Fusobacteria was significantly higher than that in non-FMT group [6.801% (1.373%, 20.586%) vs. 0.003% (0%, 9.324%), P < 0.05], and the relative abundance of Butyricimonas, Fusobacterium and Bifidobacterium at the genus level of the intestinal flora was significantly higher than that in non-FMT group [Butyricimonas: 1.634% (0.813%, 2.387%) vs. 0% (0%, 0.061%), Fusobacterium: 6.801% (1.373%, 20.586%) vs. 0.002% (0%, 9.324%), Bifidobacterium: 0.037% (0%, 0.153%) vs. 0% (0%, 0%), all P < 0.05]. KEGG metabolic pathway analysis showed that the intestinal flora of FMT group was changed in bisphenol degradation, mineral absorption, phosphonate and phosphinate metabolism, cardiac muscle contraction, Parkinson disease and other metabolic pathways and diseases. Correlation analysis showed that Actinobacteria and prealbumin (PA) in intestinal flora of FMT group were significantly positively correlated (r = 0.53, P = 0.043), Bacteroidetes was positively correlated with blood urea nitrogen (BUN; r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Firmicutes was positively correlated with BUN (r = 0.56, P = 0.029) and complement C3 (r = 0.57, P = 0.027), Fusobacteria was significantly positively correlated with immunoglobulin M (IgM; r = 0.71, P = 0.003), Proteobacteria was significantly positively correlated with procalcitonin (PCT; r = 0.63, P = 0.012) and complement C4 (r = 0.56, P = 0.030). CONCLUSIONS FMT can reduce TG level, reconstruct intestinal microecological structure, change body metabolism and function, and alleviate inflammatory response by reducing the relative abundance of harmful bacteria in patients with severe pneumonia during the convalescence period.
Humans ; Fecal Microbiota Transplantation ; Complement C3 ; Convalescence ; Prospective Studies ; Feces

Humans ; Depressive Disorder, Major ; Motor Cortex ; Magnetic Resonance Imaging

Objective To retrieve,evaluate and integrate evidence related to prevention and management of lifestyle-related dry eye patients.Methods The clinical decisions,recommended practices,evidence summaries,technical reports,guidelines,expert consensuses and systematic evaluations on the prevention and management of lifestyle-related dry eye patients in domestic and foreign databases were retrieved by the computer.The evidence was extracted and summarized according to the subject after the independent literature quality evaluation by 2 researchers.The literature retrieval time limit was from the establishment of the databases to September 2022.Results According to the inclusion criteria,13 pieces of the literature were screened,including 1 guideline,5 systematic reviews,3 expert consensuses,2 technical reports and 2 evidence summaries.Through literature reading,evidence extraction and classification,a total of 25 pieces of evidence were summarized,including assessment,symptom identification,identification of risk factors,artificial tear management,eye care,diet management,health guidance,follow-up education.Conclusion This study summarized the best evidence of prevention and management of lifestyle-related dry eye patients,so as to provide references for nurses to carry out clinical practice.In the process of evidence transformation,the actual situation should be combined to improve the quality of nursing.

Linarin, as a natural coumponent belongs to flavonoid glycoside, is widely existed in herbal plants such as chrysanthemum indicum and Mongolian flower, which has a variety of pharmacological effects, such as anti-inflammation, anti-cancer, liver protection, analgesia, antipyretic, anti-oxidation, anti-apoptosis, sedation and sleep, neuroprotection, preventing and treating hypertension, treatingdiabetes, preventing and treating osteoporosis, whitening, skin care and sunscreen. It is difficult to dissolve in water and has poor oral efficacy, but when combined with different substances or combined (forming phospholipid complex), its bioavailability can be improved, so as to improve its pharmacological efficacy.

OBJECTIVE: To study the effect of nanohydroxyapatite (nHA) for promoting surface mineralization of demineralized dentin discs and adsorption of lead ions in simulated sewage water. METHODS: Sixty dentin disks were prepared from freshly extracted teeth with intact crown (including 30 premolars and 30 molars) and treated with 10% citric acid for 2 min to simulate dentinal tubules with dentin hypersensitivity. The etched dentin discs were brushed with distilled water, 0.2 g HA or 0.2 g nHA for 2 min twice a day for 7 consecutive days, after which scanning electron microscopy (SEM) was performed and calcium and phosphorus contents in the dentin discs were detected using EDS. Lead ion adsorption capacities of HA and nHA were tested by mixing 1 mL serial concentrations of HA and nHA suspensions with 50 mL lead ion solutions (1.0 mg/L). After 24 h, the residual lead ion concentration in the supernatant was measured using ICP to calculate lead ion adsorption rate and adsorption capacity of the materials. RESULTS: SEM showed a smooth surface and empty dentin tubules in the acid- etched dentin dics. The dentin dics treated with HA were covered with masses of particles that loosely attached to the surface, and the diameter of the dentin tubules was reduced. In nHA group, the dentin discs showed a fine and homogeneous surface clogging with a tight attachment, and the dentin tubule diameter was obviously reduced. Daily brushing with HA and nHA, especially the latter, significantly increased calcium and phosphorus contents on the surface of the dentin dics ( < 0.000). In lead ion adsorption experiment, the lead ion adsorption rate of HA decreased as its concentration increased with the highest adsorption rate of 83.01%; the adsorption rate of nHA increased with its concentration until the adsorption equilibrium was reached, and its highest adsorption rate was 98.79%. A good liner relationship was found between the adsorption ability and concentration of HA. CONCLUSIONS Compared with HA, nHA has a better capacity for surface mineralization of acid-etched dentin discs and also a better ability of lead ion adsorption.

OBJECTIVE: To explore the correlation between altered levels of neurotransmitters in the frontal lobe and hippocampus and behavioral abnormalities in a Clock variant mice modeling bipolar disorder manic disorder. METHODS: Open field test and Elevated plus-maze test were carried out on the Clock mutant and wild-type control groups. The frontal lobe and hippocampus of Clock mutant mice and controls were dissected, and neurotransmitters in tissue extracts were analyzed by high-performance liquid chromatography and mass spectrometry. The concentration of neurotransmitters and behavioral indicators were assessed by t test and Pearson correlation analysis using SPSS 22.0. RESULTS: The Clock mutant mice showed a significant increase in activity, albeit with no difference in the level of anxiety from the wild-type controls, which suggested that the Clock mutant mice can be used as a model for manic attack of bipolar disorder. Altered neurotransmitter levels were detected in the frontal and hippocampal regions, including elevated histamine in the left hippocampus, reduced histamine in the right hippocampus, reduced gamma-aminobutyric acid (GABA) in bilateral hippocampus, elevated dihydroxyphenylalanine (DOPA) in the left frontal lobe and reduced DOPA in the right hippocampus, and decreased glutamine in bilateral frontal lobes. The reduced glutamine in the left frontal lobe and GABA in the right hippocampus correlated with the increased activity of Clock mutant mice. CONCLUSION Clock mutant mice showed abnormal behavior with increased activity. Reduced glutamine in the left frontal lobe and GABA in the right hippocampus were correlated with increased activity.

Bronchial asthma is characterized by airway inflammation, bronchial hyperresponsiveness, and recurrent episodes of reversible airway obstruction. Due to different pathophysiological mechanisms, the disease is very heterogeneous in clinical manifestation, course of disease, response to treatment, phenotype etc. There is a strong need for biomarkers to assess the characteration and severity of the disease. Recently, lymphocyte and blood cells, antibodies, cytokines, chemokines, noncoding RNA and other protein markers have been studied as blood biomarkers of asthma. The present article summarized these biomarkers in diagnosis, phenotyping and treatment efficacy.

Objective:To explore the effect of artificial intelligence teaching-picture system in training the bone marrow cell morphological reading ability of clinical medical students.Methods:A total of 110 five-year undergraduate students were divided into experimental group (artificial intelligence picture teaching method) and control group (traditional teaching method) in the bone marrow cell morphology reading ability training. On the basis of multimedia teaching, the experimental group was given the teaching by using the bone marrow cell morphology picture storage and transmission system for retrieval, learning and computer adaptive test. Then objective evaluation of image recognition ability and questionnaire were used to compare the teaching effect.Results:The image recognition ability was significantly better in the experimental group than in the control group [(89.6±5.7) vs. (81.4±4.9), P<0.01]. Furthermore, the experimental group showed more obvious advantages in cell morphology recognition [(74.7±4.0) vs. (68.7±4.9)] and diagnosis of hematological diseases [(14.9±3.0) vs. (12.9±2.4)] than the control group (both P<0.01). Questionnaire survey showed that the students expressed their affirmation and support for the artificial intelligence teaching-picture system in the bone marrow cell morphological reading ability training. Conclusion:The application of artificial intelligence teaching-picture system can greatly improve the teaching effect, mobilize students' learning enthusiasm and expand learning resources, which is worthy of further promotion and application.