Objective Construction of an immune-tumor dual humanized mouse model to explore the role of targeting monoamine oxidase A(MAOA)in the immune microenvironment of prostate cancer.Methods Bioinformatics analysis was used to examine the relationship between MAOAhigh cancer associated fibroblasts(CAFs)and T cells in prostate cancer.Multiplex immunofluorescence was employed to analyze the relationship between stromal MAOA expression and CD8+T cells.An immune-tumor dual humanized mouse model was constructed for in vivo verification of the infiltration of CD8+T cells in response to the targeting of stromal MAOA.Results MAOA expression in the stroma was inversely proportional to the infiltration of CD8+T cells.Inhibiting MAOA expression in the stroma enhanced the infiltration of CD8+T cells in vivo,which may reflect suppression of the accumulation of collagen in the tumor microenvironment.Conclusions Stromal MAOA plays an important role in the immunosuppressive microenvironment of prostate cancer,and its inhibition may promote the infiltration of immune cells.MAOA inhibitors have therapeutic potential in immune combination therapy for patients with prostate cancer.

[Purpose]To analyze the diagnostic yield of quantitative fecal immunochemical test(FIT)at different cut-offs in colorectal cancer(CRC)screening.[Methods]The sequential screening method was adapted in Jiashan CRC screening program for local residents aged 40～74 years old,which included a quantitative FIT and high-risk factor questionnaire for primary screening and subsequent colonoscopy for the diagnostic screening.Subjects who participated in quantitative FIT were included in this study between September,2021 and August,2023.The positive predictive values(PPVs)for colorectal neoplasms were calculated at the cut-offs of 100,120,140,160,180 and 200 ng/mL of FIT.The Cochran-Armitage trend test was performed to compare the trend of PPVs at different cut-offs.The effects of different starting age and FIT cut-offs on requirement of colonoscopy and advanced neoplasia detection were assessed.[Results]A total of 58 256 individuals completed the quantitative FIT,and 3 106 had fecal hemoglobin concentrations＞100 ng/mL,among whom 2 186 underwent colonoscopic examination with a compliance rate of 70.38％.The colonoscopy detected 588 cases of non-advanced adenomas and 355 cases of advanced neoplasms(AN),in-cluding 30 cases of CRC and 325 cases of advanced adenomas.Progressively increasing the cut-off showed a decrease in PPVs of non-advanced adenomas and an increase of AN.The ratio of the rate of reduced requirement of colonoscopy to the missed rate of the progressive lesions was the smallest when the screening start age was 45 years old and the positive FIT threshold was set at 100 ng/mL.[Conclusion]There were significant differences in the diagnostic yield at different cut-offs of FIT.Increasing the cut-offs of FIT will elevate PPVs for the advanced neoplasms.

[Purpose]To analyze the diagnostic yield of quantitative fecal immunochemical test(FIT)at different cut-offs in colorectal cancer(CRC)screening.[Methods]The sequential screening method was adapted in Jiashan CRC screening program for local residents aged 40～74 years old,which included a quantitative FIT and high-risk factor questionnaire for primary screening and subsequent colonoscopy for the diagnostic screening.Subjects who participated in quantitative FIT were included in this study between September,2021 and August,2023.The positive predictive values(PPVs)for colorectal neoplasms were calculated at the cut-offs of 100,120,140,160,180 and 200 ng/mL of FIT.The Cochran-Armitage trend test was performed to compare the trend of PPVs at different cut-offs.The effects of different starting age and FIT cut-offs on requirement of colonoscopy and advanced neoplasia detection were assessed.[Results]A total of 58 256 individuals completed the quantitative FIT,and 3 106 had fecal hemoglobin concentrations＞100 ng/mL,among whom 2 186 underwent colonoscopic examination with a compliance rate of 70.38％.The colonoscopy detected 588 cases of non-advanced adenomas and 355 cases of advanced neoplasms(AN),in-cluding 30 cases of CRC and 325 cases of advanced adenomas.Progressively increasing the cut-off showed a decrease in PPVs of non-advanced adenomas and an increase of AN.The ratio of the rate of reduced requirement of colonoscopy to the missed rate of the progressive lesions was the smallest when the screening start age was 45 years old and the positive FIT threshold was set at 100 ng/mL.[Conclusion]There were significant differences in the diagnostic yield at different cut-offs of FIT.Increasing the cut-offs of FIT will elevate PPVs for the advanced neoplasms.

Objective Construction of an immune-tumor dual humanized mouse model to explore the role of targeting monoamine oxidase A(MAOA)in the immune microenvironment of prostate cancer.Methods Bioinformatics analysis was used to examine the relationship between MAOAhigh cancer associated fibroblasts(CAFs)and T cells in prostate cancer.Multiplex immunofluorescence was employed to analyze the relationship between stromal MAOA expression and CD8+T cells.An immune-tumor dual humanized mouse model was constructed for in vivo verification of the infiltration of CD8+T cells in response to the targeting of stromal MAOA.Results MAOA expression in the stroma was inversely proportional to the infiltration of CD8+T cells.Inhibiting MAOA expression in the stroma enhanced the infiltration of CD8+T cells in vivo,which may reflect suppression of the accumulation of collagen in the tumor microenvironment.Conclusions Stromal MAOA plays an important role in the immunosuppressive microenvironment of prostate cancer,and its inhibition may promote the infiltration of immune cells.MAOA inhibitors have therapeutic potential in immune combination therapy for patients with prostate cancer.

Objective To analyze the prevalence and risk factors of sleep apnea syndrome (SAS) in patients with Alzheimer's disease (AD), and to provide theoretical basis for the prevention of SAS in AD patients. Methods A total of 130 AD patients admitted to the Department of Neurology of Guang'an People's Hospital of Sichuan Province from January 2019 to September 2022 were selected and divided into control group (without SAS) and observation group (with SAS) according to whether the patients were complicated with SAS{AHI ≥5 times/h}. Snoring, waking at night, dry mouth in the morning, AHI and SaO2 values were compared between the two groups. Clinical data of AD patients, including age, gender, body mass index (BMI), AD course, tobacco and alcohol history, and neurodegenerative diseases, were collected by self-made questionnaire and consulting the patient's electronic medical record bed. Univariate analysis and logistic regression were used to analyze the independent risk factors for SAS in AD patients. Results Among 130 AD patients, 43 cases (33.08%) of SAS occurred. The proportion of snoring, awakening at night, dry mouth in the morning and AHI value in the observation group were significantly lower than those in the control group (P<0.05). SaO2 value in observation group was significantly lower than that in control group (P<0.05). There were significant differences in age, duration of AD, BMI, smoking history, combined hypertension, neurodegenerative disease, PSQI score and PSQI score between the two groups (P<0.05). Multivariate logistic regression analysis showed that BMI≥28 kg/m², PSQI score >16 points and CDR score ≥2 points were independent risk factors for SAS in AD patients (P<0.05). Conclusion The incidence of SAS associated with AD is higher, and the main risk factors are BMI≥28 kg/m², PSQI score >16 and CDR score. Polysomnosis monitoring should be performed regularly to prevent SAS.

Background Air pollution is related to the occurrence and development of mental diseases. Olfactory bulb damage might be the potential prodromal symptom and sign of these diseases. The toxicity of diesel exhaust (DE), one of the main sources of air pollution, on olfactory bulb and the underlying mechanisms remain to be elucidated. Objective To explore the toxicity of DE on mouse olfactory bulb and underlying mechanisms. Methods A total of 40 C57BL/6 mice were randomly divided into four groups for exposure to DE by systemic inhalation: control group (filtered air), low exposure group (750 μg·m⁻³ DE), medium exposure group (1500 μg·m⁻³ DE), and high exposure group (3000 μg·m⁻³ DE). The mouse inhalation exposure to DE was performed 1 h per day for 28 d. HE staining was performed to observe pathological changes in mouse olfactory bulb tissue. TUNEL assay was used to observe apop-tosis in olfactory bulb. Kyoto Encyclopedia of Genes and Genomes (KEGG) was exhibited to explore potential mechanisms of olfactory bulb damage associated with DE. Quantitative real-time PCR (qPCR) was used to determine mRNA expression levels of inflammatory factors including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Immunofluorescence staining was conducted to observed the microglia and astrocyte activation in olfactory bulb. Results The HE staining results showed that the number of periglomerular cells in the glomerular layer of olfactory bulb decreased in a dose-dependent manner, and the cells in the granule cell layer of olfactory bulb became disordered after DE exposure. The TUNEL staining showed that TUNEL positive cells in olfactory bulb tissue and neuronal apoptosis increased in the exposed groups compared with the control group (P＜0.05). The KEGG pathway analysis showed that DE associated with significant enrichment of TNF signaling pathway in olfactory bulb tissue. The qPCR results showed that the TNF-α relative expression level significantly increased by 67% and the IL-6 relative expression level by 340% in the DE high exposure dose group compared with the control group (P＜0.05). According to the immunofluorescence staining results, the numbers of activated microglia and astrocytes in olfactory bulb tissue significantly increased in the DE high exposure group, the relative fluorescence intensity of ionized calcium binding adaptor molecule 1 (IBA-1) increased by 120%, the granule cell layer relative fluorescence intensity of glial fibrillary acidic protein (GFAP) increased by 400%, and the glomerular layer relative fluorescence intensity of GFAP increased by 240% than those in the control group (P＜0.05). Conclusion Inhalation exposure to DE can lead to glial cell activation including microglia and astrocytes in olfactory bulb tissue by activating inflammatory pathways and releasing inflammatory factors TNF-α and IL-6, leading to neuronal apoptosis in olfactory bulb tissue.

In order to explore the antitumor effect and mechanism of different extracts of cultivated Phellinus vaninii fruit body on H₂₂ tumor bearing mice, 150 ICR mice were randomly divided into blank group, model group, CTX group, P. vaninii water extract group, ethanol extract group, petroleum ether extract group and crude polysaccharide group. H₂₂ liver cancer cells were used to establish a solid tumor model and the mice were sacrificed on the 10th day after administration. The spleen and thymus organ index and tumor inhibition rate were calculated, the serum levels of TNF-α, INF-γ, VEGF, and hematoxylin-eosin were detected, and the immunohistochemical staining method was used to observe the pathological changes of tumor tissues, while Western blotting was used to detect the expression of tumor-related proteins. The high-dose petroleum ether extract group showed the best tumor inhibition rate (73.21%), increased serum levels of TNF-α, IFN-γ, and VEGF, as well as significantly promoted tumor necrosis and ablation. The immunohistochemistry of the water extract group showed negative regulation, indicating an insignificant tumor suppression. Western blotting showed the apoptosis genes Caspase-3, Caspase-9 and pathway genes NF-κB and JAK were all highly expressed in each administration group compared with the model group, and their expression levels gradually decreased with increasing doses. In summary, the petroleum ether extract of P. vaninii fruit body showed a significant anti-tumor effect which is presumably mediated through the mitochondrial pathway. The metabolism of drug in the body induces activation of Caspase-3 and Caspase-9 apoptotic proteins by Bax, Bcl-2, and TNF, which further caused nuclear chromatin or DNA to condense or degrade, and subsequently destroy the normal proliferation of tumor cells, thereby inducing their apoptosis and inhibiting tumor growth.
Animals ; Apoptosis ; Basidiomycota ; Mice ; Mice, Inbred ICR ; Neoplasms/metabolism*

Objective This study aimed to examine and propagate the medication experience and group formula of traditional Chinese medicine (TCM) Master XIONG Jibo in diagnosing and treating arthralgia syndrome (AS) through data mining. Methods Data of outpatient cases of Professor XIONG Jibo were collected from January 1, 2014 to December 31, 2018, along with cases recorded in A Real Famous Traditional Chinese Medicine Doctor: XIONG Jibo's Clinical Medical Record 1, which was published in December 2019. The five variables collected from the patients’ data were TCM diagnostic information, TCM and western medicine diagnoses, syndrome, treatment, and prescription. A database was established for the collected data with Excel. Using the Python environment, a customized modified natural language processing (NLP) model for the diagnosis and treatment of AS by Professor XIONG Jibo was established to preprocess the data and to analyze the word cloud. Frequency analysis, association rule analysis, cluster analysis, and visual analysis of AS cases were performed based on the Traditional Chinese Medicine Inheritance Computing Platform (V3.0) and RStudio (V4.0.3). Results A total of 610 medical records of Professor XIONG Jibo were collected from the case database. A total of 103 medical records were included after data screening criteria, which comprised 187 times (45 kinds) of prescriptions and 1 506 times (125 kinds) of Chinese herbs. The main related meridians were the liver, spleen, and kidney meridians. The properties of Chinese herbs used most were mainly warm, flat, and cold, while the flavors of herbs were mainly bitter, pungent, and sweet. The main patterns of AS included the damp heat, phlegm stasis, and neck arthralgia. The most commonly used herbs for AS were Chuanniuxi (Cyathulae Radix), Huangbo (Phellodendri Chinensis Cortex), Cangzhu (Atractylodis Rhizoma), Qinjiao (Gentianae Macrophyllae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangqi (Astragali Radix), and Chuanxiong (Chuanxiong Rhizoma). The most common effect of the herbs was “promoting blood circulation and removing blood stasis”, followed by “supplementing deficiency (Qi supplementing, blood supplementing, and Yang supplementing)”, and “dispelling wind and dampness”. The data were analyzed with the support ≥ 15% and confidence = 100%, and after de-duplication, five second-order association rules, 39 third-order association rules, 39 fourth-order association rules, and two fifth-order association rules were identified. The top-ranking association rules of each were “Cangzhu (Atractylodis Rhizoma) → Huangbo (Phellodendri Chinensis Cortex)” “Cangzhu (Atractylodis Rhizoma) + Chuanniuxi (Cyathulae Radix) → Huangbo (Phellodendri Chinensis Cortex)” “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) + Gancao (Glycyrrhizae Radix et Rhizoma) → Qinjiao (Gentianae Macrophyllae Radix)” and “Chuanniuxi (Cyathulae Radix) + Danggui (Angelicae Sinensis Radix) +Gancao (Glycyrrhizae Radix et Rhizoma) + Huangbo (Phellodendri Chinensis Cortex) → Qinjiao (Gentianae Macrophyllae Radix)”, respectively. Five clusters were obtained using cluster analysis of the top 30 herbs. The herbs were mainly drying dampness, supplementing Qi, and promoting blood circulation. The main prescriptions of AS were Ermiao San (二妙散), Gegen Jianghuang San (葛根姜黄散), and Huangqi Chongteng Yin (黄芪虫藤饮). The herbs of core prescription included Cangzhu (Atractylodis Rhizoma), Chuanniuxi (Cyathulae Radix), Gancao (Glycyrrhizae Radix et Rhizoma), Huangbo (Phellodendri Chinensis Cortex), Mugua (Chaenomelis Fructus), Qinjiao (Gentianae Macrophyllae Radix), Danggui (Angelicae Sinensis Radix), and Yiyiren (Coicis Semen). Conclusion Clearing heat and dampness, relieving collaterals and pain, and invigorating Qi and blood are the most commonly used therapies for the treatment of AS by Professor XIONG Jibo. Additionally, customized NLP model could improve the efficiency of data mining in TCM.

Objective To analyze the influencing factors of stunting in children under 5 years old in Jilin province in 2013,with an attempt to further improve the nutrition status among children. Methods Data on stunting in children under 5 years old in Jilin province were extracted from the National Health Services Survey 2013 in Jilin province. The influencing factors of stunting were analyzed by using univariate analysis and Logistic regression analysis.. Results The stunting prevalence in children under 5 years old was 23.8% in 2013. Univariate analysis showed that urban residence (OR=0.38,95% CI=0.25-0.57),high income (OR=0.40,95% CI=0.24-0.66),mother's education level (higher than primary school) (OR=0.50,95% CI=0.32-0.81),safe water coverage (OR=0.41,95% CI=0.22-0.75),and clean toilet coverage (OR=0.36,95% CI=0.24-0.53) are protective factors of stunting. After adjusting other factors,urban residence (OR=0.54,95% CI=0.31-0.94),safe water coverage (OR=0.28,95% CI=0.13-0.60),and clean toilet coverage (OR=0.40,95% CI=0.24-0.67) still showed protective effects. Conclusion The urban-rural disparity and the availability of safe water and clean toilet are the major factors of stunting among children under 5 years old in Jilin province. The major public health service program should be fully implemented to improve the nutrition status among children.

Objective CA125 has been proved to be closely related to peritoneal metastasis of gastric cancer.This study aimed to screen and identify a novel ssDNA aptamer targeting the extracellular domain of Mucin16. Methods Using capillary elec-trophoresis, we screened the aptamers targeting the synthetic peptide of the extracellular domain of Mucin16 and quantitatively deter-mined the Kd value of each cycle and the affinity of the aptamers for the synthetic peptide by CE-SELEX.Then we evaluated the ability of the obtained aptamers to target cancer cells using confocal laser imaging. Results After five cycles of screening, sequencing, af-finity determination, we obtained an ssDNA aptamer targeting the extracellular domain of Mucin16, with a Kd value of 122.7 nm and visible green fluorescent signals on the cell membrane of the human ovarian cancer cell line expressing Mucin16, but not on that of the normal hepatocytes not expressing Mucin16.This confirmed the binding ability of the aptamer to the extracellular domain of Mucin16. Conclusion A novel aptamer targeting the synthetic peptide of the extracellular domain of Mucin16 was successfully obtained by capil-lary electrophoresis, which could be used as a new agent in the diagnosis and treatment of peritoneal metastasis of gastric cancer.