Integrated computer analysis and a self-built Chinese cohort study identified GSTM2 as one survival-relevant gene in human colon cancer potentially regulating immune microenvironment.

According to a recent report by GLOBOCAN, colorectal cancer is the third most common and second most deadly cancer in 2020. In our previous proteomic study, we found that the expression of GSTM2 in colon tissues was significantly lower than that in para-cancer tissues, and its lower expression was associated with reduced overall survival rate of patients, suggesting that this gene might play a role in the occurrence of colon cancer. As a member of the detoxifying enzyme family, GSTM2 is likely to play an important role in the initiation of tumors. Whereas, the functions of GSTM2 in colon cancer are barely known. In this study, using the RNA-Seq datasets of colon cancer patients from public database (ntumor = 457, nnormal = 41), we confirmed the reduced expression of GSTM2 and its prognostic value in colon cancer. Furthermore, we used our own Chinese cohort (ntumor = 100, nnormal = 72) verified the lower GSTM2 expression in colon cancer, and also its effects on patient prognosis. Subsequently, we uncovered two potential reasons for the lower expression of GSTM2 in colon cancer tissues, including the deep deletion of GSTM2 on genome, and the up-regulation of RAD21 or SP1. Moreover, we disclosed that GSTM2 might be involved in several immune-related pathways in colon cancer, such as chemokine signaling and leukocyte transendothelial migration. Finally, we revealed that the GSTM2 expression was closely related to the immune-related scores of colon cancer and the infiltration ratios of various immune cells, suggesting that GSTM2 might regulate the development of colon cancer by modulating immune microenvironment. In conclusion, we uncovered the prognostic value of GSTM2 based on the public data and our own data, revealed its potential regulatory role in tumor immune microenvironment, and disclosed the probable reasons for its lower expression in colon cancer. The findings of our study provide a potential prognostic biomarker and drug target for clinical diagnosis and treatment of colon cancer.

Relationship between tooth loss and sarcopenia in suburban community-dwelling older adults in Shanghai and Tianjin of China.

Both sarcopenia and loss of teeth are associated with aging. The purpose of this study was to investigate potential relationships between tooth loss and sarcopenia and its components in suburban community-dwelling older adults of Shanghai and Tianjin, China. The subjects were 1494 people over 60 years of age (40.7% men; aged 71.64 ± 5.97 years) from Chongming District of Shanghai and Hangu District of Tianjin. Asian Working Group for Sarcopenia(AWGS) criteria were used to define sarcopenia. Muscle mass, muscle strength, and physical performance were assessed using a bioelectrical impedance analyzer, a grip strength test, and a four-meter walk test, respectively. The subjects were divided into groups depending on self-reported loss of teeth. Our studies found no correlation between tooth loss and sarcopenia or muscle mass. However, the walking speed of female participants with at least 10 teeth lost was 0.059 m/s slower than that of participants with fewer than 10 teeth lost (p < 0.001), and grip strength was 1.577 kg lower among male participants with at least 10 teeth lost than among males with fewer than 10 teeth lost (p = 0.023). These results are consistent with the importance of good oral hygiene in preventing declines of physical performance in older adults.

Gender-specific associations of speech-frequency hearing loss, high-frequency hearing loss, and cognitive impairment among older community dwellers in China.

BACKGROUND AND AIMS: This study aimed atinvestigating the relationship between speech-frequency hearing loss (SFHL), high-frequency hearing loss (HFHL), and cognitive impairment (CI) and then to determine whether there are any differences in gender among older community dwellers in China. METHODS: 1012 adults aged ≥ 60 years (428 males; average age, 72.61 ± 5.51 years) and living in Chongming District, Shanghai were enrolled in the study. We used the audiometric definition of hearing loss (HL) adopted by the World Health Organization (WHO). Speech-frequencies were measured at 0.5 kHz, 1 kHz, 2 kHz, and 4 kHz; high-frequencies were measured at 4 kHz and 8 kHz. Pure tone average (PTA) was measured as hearing sensitivity. Cognitive performance was measured using the mini mental state examination (MMSE). RESULTS: Our studies demonstrated a 37.6% prevalence of HL in males and a 36.0% prevalence of HL in females. Adjusted for confounding variables, the results from a multivariate analysis showed that SFHL was associated with CI in females (OR = 2.922, 95% Confidence Interval = 1.666-5.124) and males (OR = 2.559, 95% Confidence Interval = 1.252-5.232). However, HFHL was associated with CI only in females (OR = 3.490, 95% Confidence Interval = 1.834-6.643). HL was associated with poorer cognitive scores (P < 0.05). "Registration" (P < 0.05) in MMSE was associated with speech- and high-frequency hearing sensitivity. CONCLUSIONS: The associations between HL and CI varied according to gender in older community-dwellers, suggesting that different mechanisms are involved in the etiology of HL. Moreover, hearing sensitivity was negatively associated with cognition scores; therefore, early screening for HL and CI among older community-dwelling adults is advised.

Relationship between obesity-related anthropometric indicators and cognitive function in Chinese suburb-dwelling older adults.

BACKGROUND: Studies relating obesity to cognition in older people show conflicting results, which may be explained by the choice of obesity indicators. OBJECTIVES: This study aimed to investigate the relationship between obesity-related indicators and cognitive impairment, especially between different age or gender subgroups, and explore whether obesity-related indicators were related to specific cognitive domains. METHODS: This was a cross-sectional study on 1753 participants aged ≥ 60 years (41.0% men; aged 71.36 ± 5.96 years). Obesity-related indicators included body mass index (BMI), waist circumference (WC), calf circumference (CC), waist to hip ratio (WHR), waist to calf circumstance ratio (WCR), fat to fat-free mass ratio (FM/FFM). The Mini-Mental State Examination scale (MMSE) was used to assess cognitive function. Cognitive impairment was defined as a score ≤ 17 for illiterates, ≤ 20 for participants with primary school education, and ≤ 24 for those with junior high school degrees or above. Multiple logistic regression analysis was used to estimate multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Restricted cubic splines were used to analyze and visualize the linear relationships. RESULTS: The prevalence of cognitive impairment was 18.77%. In the fully adjusted model, CC was negatively associated with cognitive impairment (OR = 0.94, 95% CI: 0.90-0.98). Further analysis showed that CC correlated positively with recall and place orientation. A higher FM/FFM was found to be associated with a higher prevalence of cognitive impairment (OR: 1.44, 95%CI: 0.88-2.35, P for trend = 0.029); this association was notable in women (P for trend = 0.002) and the oldest (P for trend = 0.009), and so did the potential effect of BMI on cognitive impairment (70-80 years: P for trend = 0.011; ≥ 80 years: P for trend = 0.013). No statistically significant association was found between cognitive impairment and WC, WHR, or WCR. CONCLUSION: CC and FM/FFM were associated with cognitive impairment in older people. Future research needs to distinguish the effects of fat and muscle mass on cognitive function, with special attention to different ages and genders.

Long Sleep Duration Associated With Cognitive Impairment in Chinese Community-Dwelling Older Adults.

ABSTRACT: We aimed to examine the association between sleep duration and impaired cognitive function in different cognitive domains in Chinese community-dwelling older adults. A total of 1591 participants (≥60 years) were divided into five groups: ≤6 hours (very short sleep duration), >6 to 7 hours (short sleep duration), ≥7 to 8 hours (moderate sleep duration), >8 to 9 hours (moderately long sleep duration), and >9 hours (long sleep duration), according to sleep duration. Cognitive function was assessed using the Mini-Mental State Examination. Long sleep duration significantly increased the likelihood of cognitive impairment. In addition to attention, long sleep duration was negatively related to poorer global cognition and other cognitive domain functions. With the stratification of age groups, long sleep duration was negatively associated with other cognitive domain functions except delayed recall in older elderly (≥75 years) people, but not in younger elderly (60-74 years) people. Long sleep duration was associated with higher rates of cognitive impairment, poorer global cognition, and declined orientation, memory, language ability, and executive function in Chinese community-dwelling older adults, which was more significant in older elderly people.

Association Between Physical Performance and Cognitive Function in Chinese Community-Dwelling Older Adults: Serial Mediation of Malnutrition and Depression.

PURPOSE: We aimed to propose a serial mediational model to further analyze the relationship between poor physical performance, malnutrition, depression and cognitive impairment in Chinese community-dwelling older adults. PATIENTS AND METHODS: This study consisted of 1386 community-dwelling Chinese older adults aged 65 years and older in Shanghai, China. Mild cognitive impairment (MCI) was assessed by the Mini-Mental State Examination (MMSE) and Instrumental Activities Of Daily Living (IADL). Physical performance was assessed by short physical performance battery (SPPB). Malnutrition was defined with the Mini Nutritional Assessment (MNA). Depressive symptoms were evaluated by the 30-item Geriatric Depression Scale (GDS). Serial multiple mediator models were used. RESULTS: The mean age of the final analysis sample was 73.62±6.14, and 57.6% (n=809) were females. The prevalence of MCI was 14.35% (n=199). Physical performance (p<0.001), nutritional status (p=0.025), and depressive symptoms (p=0.002) were correlated with MCI. The serial mediational model revealed that MNA and GDS scores significantly mediated association of SPPB and MMSE scores (c'=0.4728, p<0.001). Furthermore, depressive symptoms significantly mediated the association of physical performance and cognition (p=0.0311), while malnutrition had no independent mediating effect between these two factors (p=0.794). CONCLUSION: Our study examined the serial multiple mediation roles of nutritional status and depressive symptoms on the relationship between physical performance and cognitive function in community-dwelling Chinese older adults. Older adults who were in poor physical condition tend to have worse nutritional status, more severe depression, and poorer cognitive function.

Obesity, Even in the Metabolically Healthy, Increases the Risk of Poor Physical Performance: A Cross-Sectional Study of Older People in a Chinese Community.

OBJECTIVE: We examined the association between obesity and physical performance under different metabolic status. METHODS: The sample included 1395 Chinese community-dwelling participants (mean age, 71.88 ± 5.87 years; 40.9% men). Being metabolically healthy was defined as having the presence of < 3 of 5 components of metabolic syndrome (MetS); obesity was defined as having a BMI > 28 kg/m2. Participants were divided into four groups based on BMI (non-obese/obese) and metabolic health (healthy/unhealthy). Physical performance was measured by grip strength, 4-m walking speed, and the timed up and go test (TUGT). RESULTS: After multiple adjustments, compared with metabolically healthy non-obese group, the metabolically unhealthy obese group showed lower relative grip strength, lower 4-m walking speed, and higher TUGT (P all < 0.05), and only relative grip strength of the metabolically healthy obese group was significantly lower than that of metabolically healthy non-obese (P < 0.01). Relative grip strength was negatively associated with impaired fasting glucose (ß = -0.071), elevated triglycerides (ß = -0.062), abdominal obesity (ß = -0.230) and general obesity (ß = -0.225) (P all < 0.01). Walking speed and TUGT were only associated with general obesity, rather than other metabolic components. The associations of MetS with physical performance were mainly driven by abdominal obesity. CONCLUSION: Even in those who are metabolically healthy, obesity (especially general obesity) increases the risk of poor physical performance. Elderly people with general obesity and MetS, whether in combination or alone, have an increased risk of muscle dysfunction, and that combination produces a higher risk of impaired mobility.

Cross-protective immunity against influenza A/H1N1 virus challenge in mice immunized with recombinant vaccine expressing HA gene of influenza A/H5N1 virus.

BACKGROUND: Influenza virus undergoes constant antigenic evolution, and therefore influenza vaccines must be reformulated each year. Time is necessary to produce a vaccine that is antigenically matched to a pandemic strain. A goal of many research works is to produce universal vaccines that can induce protective immunity to influenza A viruses of various subtypes. Despite intensive studies, the precise mechanisms of heterosubtypic immunity (HSI) remain ambiguous. METHOD: In this study, mice were vaccinated with recombinant virus vaccine (rL H5), in which the hemagglutinin (HA) gene of influenza A/H5N1 virus was inserted into the LaSota Newcastle disease virus (NDV) vaccine strain. Following a challenge with influenza A/H1N1 virus, survival rates and lung index of mice were observed. The antibodies to influenza virus were detected using hemagglutination inhibition (HI). The lung viral loads, lung cytokine levels and the percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in spleen were detected using real-time RT-PCR, ELISA and flow cytometry respectively. RESULTS: In comparison with the group of mice given phosphate-buffered saline (PBS), the mice vaccinated with rL H5 showed reductions in lung index and viral replication in the lungs after a challenge with influenza A/H1N1 virus. The antibody titer in group 3 (H1N1-H1N1) was significantly higher than that in other groups which only low levels of antibody were detected. IFN-γ levels increased in both group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1). And the IFN-γ level of group 2 was significantly higher than that of group 1. The percentages of both IFN-γ+CD4+ and IFN-γ+CD8+ T cells in group 1 (rL H5-H1N1) and group 2 (rL H5 + IL-2-H1N1) increased significantly, as measured by flow cytometry. CONCLUSION: After the mice were vaccinated with rL H5, cross-protective immune response was induced, which was against heterosubtypic influenza A/H1N1 virus. To some extent, cross-protective immune response can be enhanced by IL-2 as an adjuvant. Cellular immune responses may play an important role in HSI against influenza virus.