Tumor microenvironment is the result of dynamic interactions between different cellular and non-cellular components,including cancer cells themselves,extracellular matrix,immune cells and various non immune cells.Microenvironment is closely related to the growth,metastasis and prognosis of breast cancer,and is closely related to the current popular targeted therapy and immunotherapy.Radiomics is a new field of translational medicine based on extracting high-dimensional data from images to obtain reliable models that can be applied to clinical practice.In this review,the latest advances in the application of radiomics to the tumor microenvironment of breast cancer are discussed.

Tumor microenvironment is the result of dynamic interactions between different cellular and non-cellular components,including cancer cells themselves,extracellular matrix,immune cells and various non immune cells.Microenvironment is closely related to the growth,metastasis and prognosis of breast cancer,and is closely related to the current popular targeted therapy and immunotherapy.Radiomics is a new field of translational medicine based on extracting high-dimensional data from images to obtain reliable models that can be applied to clinical practice.In this review,the latest advances in the application of radiomics to the tumor microenvironment of breast cancer are discussed.

BACKGROUND:Agomelatine is a clinically proven treatment for neuropsychiatric symptoms,such as anxiety and depression.Furthermore,our previous study has demonstrated that agomelatine ameliorates cognitive behaviors,hippocampal synaptic plasticity,and brain pathology in a mouse model of Alzheimer's disease.However,it remains unclear whether agomelatine can improve anxiety and depression-like behaviors in Alzheimer's disease model mice. OBJECTIVE:To investigate the improving effects of agomelatine on anxiety-and depression-like behaviors in APP/PS1 transgenic mice and its underlying molecular mechanisms. METHODS:(1)Eighteen APP/PS1 transgenic mice were randomly divided into model control group(n=9)and model intervention group(n=9).Another wild-type mice were randomized into control group(n=9)and intervention group(n=9).Model intervention group and intervention group were intraperitoneally injected with 10 mg/kg agomelatine per day for 31 continuous days.Behavioral experiments,including the elevated cross maze and forced swimming tests,and mRNA sequencing of the hippocampus were then performed.(2)Mouse hippocampal neuronal cell lines(HT22)and brain microvascular endothelial cell lines(bEnd.3)were cultured and divided into four groups:blank group without any drug,drug group with 20 μmol/L agomelatine,model group with 10 μmol/L β-amyloid 1-42,and experimental group with 10 μmol/L β-amyloid 1-42+20 μmol/L agomelatine.After 24 hours of incubation,protein expression of S416p-tau and S9p-GSK3β in HT22 cells was detected by immunoblotting,and protein expression of low-density lipoprotein receptor-related protein 1 and glycosylation end-product receptor in bEnd.3 cells was detected by immunoblotting. RESULTS AND CONCLUSION:In the elevated plus maze test,the time spent in the open arms(P＜0.01)and the entries into open arms(P＜0.05)in the mice of model control group were evidently lower than those in the control group,whereas those were obviously increased in the model intervention group compared with the model control group(P＜0.05).Forced swimming test results showed that the immobile time exhibited a marked increase in the model control group compared with the control group(P＜0.05),but it was significantly decreased in the model intervention group compared with the model control group(P＜0.05).Hippocampal tissue mRNA sequencing showed that agomelatine enhanced the expression of low-density lipoprotein receptor-related protein 1 in the hippocampus of APP/PS1 mice.Western blot analysis revealed that the level of S416p-tau in HT22 cells was higher in the model group than the blank group(P＜0.05),while it was markedly decreased in the experimental group compared with the model group(P＜0.05);the level of S9p-GSK3β in HT22 cells was higher in the drug group than the blank group(P＜0.05)as well as higher in the experimental group than the model group(P＜0.05).Moreover,the expression of low-density lipoprotein receptor-related protein 1 in bEnd.3 cells was higher in the experimental group than the model group(P＜0.05).To conclude,agomelatine can alleviate anxiety-and depression-like behaviors in Alzheimer's disease mice by promoting the clearance of β-amyloid and phosphorylated tau.

Objective:To explore the characteristics of gut microbiota changes in individuals with Sarcopenic Obesity(SO)based on 16S rRNA sequencing.Methods:This cross-sectional study was conducted in Chongming District, Shanghai from April to November 2021.Fecal samples were collected from 20 elderly SO patients (case group)and 40 elderly non-SO individuals(control group)for 16S rRNA sequencing in order to analyze the diversity, structural composition, and species differences of gut microbiota, and then to predict the differential metabolic functions of the gut microbiota.Results:A total of 60 subjects were included.The case group consisted of 20 individuals(15 males and 5 females)with an average age of 73.15 ± 4.09 years; the control group included 40 individuals(20 males and 20 females)with an average age of 71.20 ± 4.12 years.The α-diversity analysis revealed that the richness indices ACE and Chao 1 of the case group were significantly lower than those of the control group( P<0.05), while the diversity indices Shannon and Simpson showed a trend of being lower in the case group, but the differences were not statistically significant( P>0.05). Principal coordinate analysis based on the Unweighted-unifrac distance metric demonstrated a statistically significant difference in β-diversity between the two groups( P=0.003). The structure and composition of the gut microbiota in the case group were altered, with a significant reduction in the relative abundance of the Blautia genus in the case group( P<0.05). LEfSe analysis identified 5 and 16 enriched microbial species in the case and control groups, respectively (Linear Discriminant Analysis score >2, P<0.05). Additionally, PICRUSt2 functional prediction revealed significant differences( P<0.05)in metabolic pathways between the two groups, including quorum sensing, fat digestion and absorption, and folate biosynthesis. Conclusions:The gut microbiota in elderly SO patients is disordered, mainly manifested as a decrease in diversity and characteristic changes in structural composition, as well as a reduction in the abundance of the beneficial bacterium Blautia.The Progression of SO is closely associated with gut microbiota metabolic disturbances, and targeting the gut microbiota is expected to become a novel therapeutic approach for SO.

Objective:To explore the split-face phenomenon in patients with bulbar-involved amyotrophic lateral sclerosis (ALS) through clinical and electrophysiological studies.Methods:A total of 52 clinically definite and clinically probable cases of bulbar-involved ALS, diagnosed according to the World Federation of Neurology El Escorial criteria, were retrospectively collected in the Third Central Hospital of Tianjin from September 2019 to November 2022. And 58 patients with idiopathic facial nerve paralysis with onset time≤7 days who visited the Department of Neurology of the Third Central Hospital of Tianjin during the same period were collected as control group. The firm eye closure (FC) score and cheek bulge (CB) score were used to assess the clinical involvement of facial muscles (dividing into facial muscle involvement group and non-facial muscle involvement group) and the presence of the split-face phenomenon (strong eye closure and weak cheek bulging) in ALS patients. The compound muscle action potential (CMAP) amplitudes of the bilateral orbicularis oculi and orbicularis oris muscles were measured using the Nicolet EDX Viking electromyography/evoked potential system. The CMAP amplitude ratio was calculated. The facial nerve electrophysiological differences were compared between ALS patients with bulbar involvement and patients with idiopathic facial nerve paralysis. The analysis of electrophysiological data across various groups was carried out utilizing the Kruskal-Wallis H test, while pairwise comparisons between groups were executed employing the Bonferroni correction method. Additionally, a stepwise binary Logistic regression analysis was implemented to ascertain the factors associated with facial muscle involvement in patients with bulbar-involved ALS. The receiver operating characteristic (ROC) curve was used to assess the diagnostic accuracy of facial nerve electrophysiological testing in diagnosing ALS in the presence of symptoms of facial muscle involvement. Results:Among the 52 ALS patients with bulbar involvement, there were 20 cases (38.5%) with facial muscle involvements, all of which were bilateral; 16 patients (30.8%) exhibited weakness solely in the ability to puff their cheeks, 1 patient (1.9%) presented with weakness exclusively in closing the eyes, and 3 patients (5.8%) experienced weakness in both closing the eyes and puffing the cheeks. The Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score of the facial muscle involvement group was lower compared to the non-facial muscle involvement group (36.90±9.20 vs 40.75±5.21, t=2.419, P=0.019), while the FC score and CB score were higher in the facial muscle involvement group [FC score: 0(0, 1) vs 0(0, 0), U=5.854, P<0.001; CB score: 4(3, 4) vs 0(0, 0), U=9.069, P<0.001], showing statistically significant differences. There was no statistically significant difference in the CMAP amplitude of the orbicularis oculi muscle between the facial muscle involvement group and the healthy side of the idiopathic facial nerve paralysis group, the affected side of the idiopathic facial nerve paralysis group, and the non-facial muscle involvement group (all P>0.05). The CMAP amplitude of the orbicularis oris muscle in the facial muscle involvement group [1 100.00 (775.00, 1 375.00) μV] was lower than that in the healthy side of the idiopathic facial nerve paralysis group [1 800.00 (1 400.00, 2 300.00) μV] and the non-facial muscle involvement group [1 555.00 (1 202.50, 1 980.00) μV], with statistically significant differences ( H=5.884, P<0.001; H=4.114, P<0.001). There was no statistically significant difference in the CMAP amplitude of the orbicularis oris muscle between the facial muscle involvement group and the affected side of the idiopathic facial nerve paralysis group ( P>0.05). The CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles in the facial muscle involvement group [0.83(0.51, 1.14)] was higher than that in the healthy side of the idiopathic facial nerve paralysis group [0.55(0.39, 0.73)], the affected side of the idiopathic facial nerve paralysis group [0.57(0.40, 0.73)], and the non-facial muscle involvement group [0.60(0.42, 0.71)], with statistically significant differences ( H=-3.440, P=0.003; H=-3.433, P=0.004; H=-3.225, P=0.008). Logistic regression analysis revealed that the CMAP amplitude of orbicularis oris muscle ( OR=0.998,95% CI 0.997-0.999, P<0.001) and ALSFRS-R score ( OR=0.916,95% CI 0.857-0.979, P=0.010) were factors associated with facial muscle involvement in ALS patients with bulbar involvement. The ROC curve analysis results showed that the area under the curve (AUC) of the orbicularis oculi muscle CMAP was 0.629, the AUC of the orbicularis oris muscle CMAP was 0.838, and the AUC of the CMAP amplitude ratio of the orbicularis oculi/orbicularis oris muscles was 0.690 in the facial muscle involvement group. Conclusions:Patients with bulbar-involved ALS have split-face phenomenon characterized by strong eye closure and weak cheek bulging. When bulbar-involved ALS patients have symptoms of facial muscle involvement, the CMAP amplitude of the orbicularis oris muscle decreases significantly, whereas the CMAP amplitude of the orbicularis oculi muscle remains relatively stable, further illustrating the split phenomenon.

Objective:To analyze the clinical and electrophysiological characteristics of patients with sensory neuronopathies (SNN), and to evaluate the significance of electrophysiological markers in the diagnosis and assessment of disease progression.Methods:A retrospective analysis was performed to evaluate the clinical manifestations, electrophysiological characteristics, and spinal cord magnetic resonance imaging (MRI) features of 8 cases diagnosed with SNN at the Third Central Hospital of Tianjin between 2015 and 2023. The neurophysiological examination mainly included limb nerve conduction study (NCS), same core needle electrode electromyography, somatosensory evoked potential (SEP), skin sympathetic reflex (SSR), and contact heat evoked potential (CHEP).Results:Among the 8 cases with SNN, 7 cases exhibited asymmetrical onset and a non-length-dependent pattern. All the 8 cases presented with severe deep sensory ataxia, accompanied by superficial sensory abnormalities and tendon areflexia. Paraneoplastic SNN were the most prevalent etiological subtype (4 cases), all of whom presented peripheral neuropathy as the initial symptom. Among these 4 cases, malignancies were identified in 3 cases and 3 cases presented with anti-Hu antibodies. Among the remaining 4 patients, 2 cases were autoimmune and the other 2 cases were idiopathic. NCS results of the 8 cases revealed decrease or absence of sensory nerve action potential (SNAP) amplitudes, with normal sensory conduction velocities. Six cases showed abnormal SEP, including 2 cases of central damage and 4 cases of peripheral damage, 5 cases had abnormal SSR, and 2 cases exhibited abnormal CHEP. Motor nerve conduction studies were normal in all 8 cases. Six patients underwent spinal MRI, and 4 exhibited abnormal signals in dorsal columns.Conclusions:The hallmark clinical manifestation of SNN is sensory ataxia, characterized by substantial impairment of superficial sensation, typically manifesting in a non-length-dependent distribution. Beyond the widespread and significant reduction in SNAP amplitudes, SNN may also exhibit additional electrophysiological impairments, such as those observed in SEP, SSR and CHEP.SEP combined with spinal cord MRI can improve the detection rate for damages in the central sensory conduction pathway.

BACKGROUND: Meningeal metastasis (MM) is a form of malignant metastasis where tumor cells spread from the primary site to the pia mater, dura mater, arachnoid, subarachnoid space, and other cerebrospinal fluid compartments. Lung cancer is one of the most common malignant tumor types with MM. MM not only signifies that the lung cancer has progressed to an advanced stage but also leads to a range of severe clinical symptoms due to meningeal involvement. Currently, the risk factors associated with the development of MM are not fully elucidated. The aim of this study was to investigate the risk factors for MM in patients with lung adenocarcinoma (LUAD) who underwent non-surgical interventions, in order to identify LUAD patients at high risk for MM. METHODS: This retrospective study analyzed the clinical data of patients diagnosed with LUAD at the First Affiliated Hospital of Zhengzhou University from January 2020 to July 2024. Missing data were imputed using multiple imputation methods, and risk factors were identified through LASSO, univariate, and multivariate Logistic regression analyses. RESULTS: A total of 170 patients with LUAD were included in this study and divided into two groups: 87 patients with MM and 83 patients without MM. Univariate and multivariate Logistic regression analyses revealed that younger age at diagnosis (P=0.004), presence of the epidermal growth factor receptor (EGFR) L858R gene mutation (P=0.008), and concurrent liver metastasis at baseline (P=0.004) were independent risk factors for developing MM in LUAD patients who did not undergo surgical intervention. Conversely, higher baseline globulin levels (P=0.039) and the presence of the anaplastic lymphoma kinase (ALK) gene mutation (P=0.040) were associated with a reduced risk of MM development. CONCLUSIONS Age at diagnosis, EGFR L858R mutation status, ALK gene mutation status, concurrent liver metastasis, globulin levels at baseline were significantly associated with the risk of developing MM in patients with LUAD patients who did not undergo surgical intervention. For patients diagnosed at a younger age, carrying the EGFR L858R mutation, or presenting with baseline liver metastasis, early implementation of tertiary prevention strategies for MM is crucial. Regular monitoring of MM status should be conducted in these high-risk groups.
Humans ; Male ; Adenocarcinoma of Lung/therapy* ; Female ; Middle Aged ; Risk Factors ; Lung Neoplasms/therapy* ; Retrospective Studies ; Aged ; Meningeal Neoplasms/genetics* ; Adult

Objective:To explore the correlation between smoking behavior of employees in heavy industry enterprises and risk factors for cardiovascular and cerebrovascular diseases.Methods:A cross-sectional study design was adopted. A questionnaire survey and physical examination data collection were conducted on employees of a heavy industry enterprise in Shaanxi Province using a cluster sampling method from March to April 2024. A total of 2 209 cases met the inclusion criteria. According to the smoking index (SI), participants were divided into a non-smoking group (SI=0, 1 316 cases), a low smoking group (SI400, 656 cases), and a high smoking group (SI≥400, 237 cases). According to the fagerstrom test for nicotine dependence (FTND) score, participants were divided into a non-dependence group (FTND=0, 1 316 cases), a mild dependence group (FTND=1-3, 623 cases), a moderate dependence group (FTND=4-6, 204 cases), and a severe dependence group (FTND≥7, 66 cases). Spearman rank correlation, univariate, and multivariate logistic regression analyses were used to compare differences in blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, homocysteine, and body mass index among the groups.Results:As the SI and FTND scores increased, blood pressure, low-density lipoprotein cholesterol, triglycerides, uric acid, and homocysteine all showed an increasing trend, while high-density lipoprotein cholesterol showed a decreasing trend (all P0.05). The systolic blood pressure, diastolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol (LDL-C), triglycerides, serum uric acid, and homocysteine in the high smoking group were higher than those in the non-smoking group [(124.93±16.55) vs (122.32±16.62) mmHg (1 mmHg=0.133 kPa), (80.86±11.10) vs (76.18±11.63) mmHg, 5.58 vs 5.29 mmol/L, (3.13±0.65) vs (2.95±0.56) mmol/L, 1.70 vs 1.09 mmol/L, (336.80±69.94) vs (299.00±86.43) μmol/L, 14.20 vs 11.76 μmol/L, all P0.001], the high-smoking group had lower HDL cholesterol than the non-smoking group [(1.34±0.30) vs (1.39±0.27) mmol/L, P0.001], the systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglycerides, serum uric acid, and homocysteine in the severely dependent group were higher than those in the non-dependent group [(132.09±16.69 )vs (122.32±16.62) mmHg, (81.32±12.97) vs (76.18±11.63) mmHg, 5.61 vs 5.29 mmol/L, (4.98±0.91 )vs (4.70±0.88) mmol/L, (3.19±0.62) vs (2.95±0.56) mmol/L, 1.87 vs 1.09 mmol/L, (328.95±75.21) vs (299.03±86.43) μmol/L, 14.38 vs 11.76 μmol/L, all P0.05], and the high density lipoprotein cholesterol (HDL-C) in the severely dependent group was lower than that in the non-dependent group [(1.32±0.30) vs (1.39±0.27) mmol/L, P0.001]. Multivariate analysis showed that SI and degree of tobacco dependence (DTD), were significantly correlated with fasting blood glucose, triglycerides, and LDL cholesterol, but the effect size of SI was too small ( OR=1.001, 95% CI: 1.000-1.001, P=0.002, OR=1.001, 95% CI: 1.001-1.002, P0.001, OR=1.001, 95% CI: 1.000-1.001, P=0.032). Conclusions:Smoking behavior among employees in heavy industry enterprises is significantly correlated with risk factors for cardiovascular and cerebrovascular diseases. The degree of tobacco dependence is closely related to the risk of abnormal fasting blood glucose, low-density lipoprotein cholesterol, and triglycerides.

Objective:To explore the characteristics of gut microbiota changes in individuals with Sarcopenic Obesity(SO)based on 16S rRNA sequencing.Methods:This cross-sectional study was conducted in Chongming District, Shanghai from April to November 2021.Fecal samples were collected from 20 elderly SO patients (case group)and 40 elderly non-SO individuals(control group)for 16S rRNA sequencing in order to analyze the diversity, structural composition, and species differences of gut microbiota, and then to predict the differential metabolic functions of the gut microbiota.Results:A total of 60 subjects were included.The case group consisted of 20 individuals(15 males and 5 females)with an average age of 73.15 ± 4.09 years; the control group included 40 individuals(20 males and 20 females)with an average age of 71.20 ± 4.12 years.The α-diversity analysis revealed that the richness indices ACE and Chao 1 of the case group were significantly lower than those of the control group( P<0.05), while the diversity indices Shannon and Simpson showed a trend of being lower in the case group, but the differences were not statistically significant( P>0.05). Principal coordinate analysis based on the Unweighted-unifrac distance metric demonstrated a statistically significant difference in β-diversity between the two groups( P=0.003). The structure and composition of the gut microbiota in the case group were altered, with a significant reduction in the relative abundance of the Blautia genus in the case group( P<0.05). LEfSe analysis identified 5 and 16 enriched microbial species in the case and control groups, respectively (Linear Discriminant Analysis score >2, P<0.05). Additionally, PICRUSt2 functional prediction revealed significant differences( P<0.05)in metabolic pathways between the two groups, including quorum sensing, fat digestion and absorption, and folate biosynthesis. Conclusions:The gut microbiota in elderly SO patients is disordered, mainly manifested as a decrease in diversity and characteristic changes in structural composition, as well as a reduction in the abundance of the beneficial bacterium Blautia.The Progression of SO is closely associated with gut microbiota metabolic disturbances, and targeting the gut microbiota is expected to become a novel therapeutic approach for SO.

Objective:To explore the correlation between smoking behavior of employees in heavy industry enterprises and risk factors for cardiovascular and cerebrovascular diseases.Methods:A cross-sectional study design was adopted. A questionnaire survey and physical examination data collection were conducted on employees of a heavy industry enterprise in Shaanxi Province using a cluster sampling method from March to April 2024. A total of 2 209 cases met the inclusion criteria. According to the smoking index (SI), participants were divided into a non-smoking group (SI=0, 1 316 cases), a low smoking group (SI400, 656 cases), and a high smoking group (SI≥400, 237 cases). According to the fagerstrom test for nicotine dependence (FTND) score, participants were divided into a non-dependence group (FTND=0, 1 316 cases), a mild dependence group (FTND=1-3, 623 cases), a moderate dependence group (FTND=4-6, 204 cases), and a severe dependence group (FTND≥7, 66 cases). Spearman rank correlation, univariate, and multivariate logistic regression analyses were used to compare differences in blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, uric acid, homocysteine, and body mass index among the groups.Results:As the SI and FTND scores increased, blood pressure, low-density lipoprotein cholesterol, triglycerides, uric acid, and homocysteine all showed an increasing trend, while high-density lipoprotein cholesterol showed a decreasing trend (all P0.05). The systolic blood pressure, diastolic blood pressure, fasting blood glucose, low density lipoprotein cholesterol (LDL-C), triglycerides, serum uric acid, and homocysteine in the high smoking group were higher than those in the non-smoking group [(124.93±16.55) vs (122.32±16.62) mmHg (1 mmHg=0.133 kPa), (80.86±11.10) vs (76.18±11.63) mmHg, 5.58 vs 5.29 mmol/L, (3.13±0.65) vs (2.95±0.56) mmol/L, 1.70 vs 1.09 mmol/L, (336.80±69.94) vs (299.00±86.43) μmol/L, 14.20 vs 11.76 μmol/L, all P0.001], the high-smoking group had lower HDL cholesterol than the non-smoking group [(1.34±0.30) vs (1.39±0.27) mmol/L, P0.001], the systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, low-density lipoprotein cholesterol, triglycerides, serum uric acid, and homocysteine in the severely dependent group were higher than those in the non-dependent group [(132.09±16.69 )vs (122.32±16.62) mmHg, (81.32±12.97) vs (76.18±11.63) mmHg, 5.61 vs 5.29 mmol/L, (4.98±0.91 )vs (4.70±0.88) mmol/L, (3.19±0.62) vs (2.95±0.56) mmol/L, 1.87 vs 1.09 mmol/L, (328.95±75.21) vs (299.03±86.43) μmol/L, 14.38 vs 11.76 μmol/L, all P0.05], and the high density lipoprotein cholesterol (HDL-C) in the severely dependent group was lower than that in the non-dependent group [(1.32±0.30) vs (1.39±0.27) mmol/L, P0.001]. Multivariate analysis showed that SI and degree of tobacco dependence (DTD), were significantly correlated with fasting blood glucose, triglycerides, and LDL cholesterol, but the effect size of SI was too small ( OR=1.001, 95% CI: 1.000-1.001, P=0.002, OR=1.001, 95% CI: 1.001-1.002, P0.001, OR=1.001, 95% CI: 1.000-1.001, P=0.032). Conclusions:Smoking behavior among employees in heavy industry enterprises is significantly correlated with risk factors for cardiovascular and cerebrovascular diseases. The degree of tobacco dependence is closely related to the risk of abnormal fasting blood glucose, low-density lipoprotein cholesterol, and triglycerides.