New advances of TMEM88 in cancer initiation and progression, with special emphasis on Wnt signaling pathway.

Transmembrane protein 88 (TMEM88), a newly discovered protein localized on the cell membrane. Recent studies showed that TMEM88 was involved in the regulation of several types of cancer. TMEM88 was expressed at significantly higher levels in breast cancer (BC) cell line than in normal breast cell line with co-localized with Dishevelled (DVL) in the cytoplasm of BC cell line. TMEM88 silencing in the ovarian cancer cell line CP70 resulted in significant upregulation of Wnt downstream genes (c-Myc, cyclin-D1) and other Wnt target genes including JUN, PTIX2, CTNNB1 (ß-catenin), further supporting that TMEM88 inhibits canonical Wnt signaling pathway. Wnt signaling pathway has been known to play important roles in many diseases, especially in cancer. For instance, hepatocellular carcinoma (HCC) has become one of the most common tumors harboring mutations in the Wnt signaling pathway. As the inhibitor of Wnt signaling, TMEM88 has been considered to act as an oncogene or a tumor suppressor. Up-regulated TMEM88 or gene therapy approaches could be an effective therapeutic approach against tumor as TMEM88 inhibits Wnt signaling through direct interaction with DVL. Here, we review the current knowledge on the functional role and potential clinical application of TMEM88 in the control of various cancers. Highlights Wnt signaling displays an important role in several pathogenesis of cancer. Wnt signaling pathway is activated during cancer development. TMEM88 has an impact on cancer by inhibiting canonical Wnt signaling. We discuss the importance and new applications of TMEM88 in cancer therapy.

The association between social capital and quality of life among type 2 diabetes patients in Anhui province, China: a cross-sectional study.

BACKGROUND: To investigate the association between social capital and quality of life among type 2 diabetes patients in Anhui province, China. METHODS: In a cross-sectional study, 436 adults with type 2 diabetes were interviewed. The two domains of Quality of life, physical component summary (PCS) and mental component summary (MCS), were measured using the Short-Form Health Survey (SF-36). A modified instrument scale was used to measure cognitive and structural social capital. Multiple logistic regression models were used to assess the associations between social capital and quality of life, adjusting for social economic status and risk factors for health. RESULTS: 24.3 % of participants (106) were in poor PCS and 25.0 % (109) in poor MCS. The proportions of participants who had low cognitive and structural social capital were 47.0 % (205) and 64.4 % (281), respectively. Results of logistic regression models showed that cognitive social capital was positively associated with PCS (OR = 1.84; 95 % CI: 1.12, 3.02) and MCS (OR = 1.65; 95 % CI: 1.03, 2.66). However, the associations between structural social capital and PCS (OR = 0.80, 95 % CI: 0.48, 1.34) and MCS (OR = 0.62; 95 % CI: 0.38, 1.01) were not statistically significant. CONCLUSIONS: It is the first study in China to investigate associations between quality of life and social capital in type 2 diabetes. Findings document that cognitive social capital is associated with the quality of life of type 2 diabetes patients. Our study suggests that the social capital theory may provide a new approach to increase physical resources in diabetes prevention and control, especially in Low and Middle Income countries (LMICs).

Association between interleukin-6 levels and stroke: a systematic review and meta-analysis.

OBJECTIVES: We aimed to evaluate the association of interleukin-6 (IL-6) expression levels with stroke. METHODS: According to the set search strategy, we systematically screened relevant studies using PubMed and extracted study results regarding IL-6 from the literature for comprehensive quantitative analysis to explore the relationship between IL-6 level and stroke risk. RESULTS: This study included 15 publications with a total of 1696 participants, with 975 cases in the case group and 721 cases in the control group. Meta-analysis showed that IL-6 levels were significantly higher in the stroke population than those in the control group (standardized mean difference = 1.22, 95% confidence interval = 0.79-1.64). Subgroup analysis showed that there was no significant difference in heterogeneity for IL-6 detection methods between the two groups (I2 = 0, P = 0.47). The difference in heterogeneity test results regarding geographic region was statistically significant (I2 = 89.7%, P < 0.01). The results of heterogeneity testing for mean participant age were also statistically significant (I2 = 84.3%, P = 0.01). CONCLUSION: The present study results showed that IL-6 may be significantly associated with stroke development.

Machine learning is an effective method to predict the 3-month prognosis of patients with acute ischemic stroke.

Background and objectives: Upwards of 50% of acute ischemic stroke (AIS) survivors endure varying degrees of disability, with a recurrence rate of 17.7%. Thus, the prediction of outcomes in AIS may be useful for treatment decisions. This study aimed to determine the applicability of a machine learning approach for forecasting early outcomes in AIS patients. Methods: A total of 659 patients with new-onset AIS admitted to the Department of Neurology of both the First and Second Affiliated Hospitals of Bengbu Medical University from January 2020 to October 2022 included in the study. The patient' demographic information, medical history, Trial of Org 10,172 in Acute Stroke Treatment (TOAST), National Institute of Health Stroke Scale (NIHSS) and laboratory indicators at 24 h of admission data were collected. The Modified Rankine Scale (mRS) was used to assess the 3-mouth outcome of participants' prognosis. We constructed nine machine learning models based on 18 parameters and compared their accuracies for outcome variables. Results: Feature selection through the Least Absolute Shrinkage and Selection Operator cross-validation (Lasso CV) method identified the most critical predictors for early prognosis in AIS patients as white blood cell (WBC), homocysteine (HCY), D-Dimer, baseline NIHSS, fibrinogen degradation product (FDP), and glucose (GLU). Among the nine machine learning models evaluated, the Random Forest model exhibited superior performance in the test set, achieving an Area Under the Curve (AUC) of 0.852, an accuracy rate of 0.818, a sensitivity of 0.654, a specificity of 0.945, and a recall rate of 0.900. Conclusion: These findings indicate that RF models utilizing general clinical and laboratory data from the initial 24 h of admission can effectively predict the early prognosis of AIS patients.

Genomic and phenotypic characterization of Streptococcus mutans isolates suggests key gene clusters in regulating its interaction with Streptococcus gordonii.

Streptococcus mutans (S. mutans) is one of the primary pathogens responsible for dental caries. Streptococcus gordonii (S. gordonii) is one of the early colonizers of dental plaque and can compete with S. mutans for growth. In the present analysis, we explored key target genes against S. gordonii in S. mutans using 80 S. mutans clinical isolates with varying capabilities against S. gordonii. A principal coordinate analysis revealed significant genetic diversity differences between antagonistic and non-antagonistic groups. Genomic comparisons revealed 33 and 61 genes that were, respectively, positively and negatively correlated with S. mutans against S. gordonii, with RNA-sequencing (RNA-seq) highlighting 11 and 43 genes that were, respectively, upregulated and downregulated in the antagonistic group. Through a combination of these results and antiSMASH analysis, we selected 16 genes for qRT-PCR validation in which the expression levels of SMU_137 (malate dehydrogenase, mleS), SMU_138 (malate permease, mleP), SMU_139 (oxalate decarboxylase, oxdC), and SMU_140 (glutathione reductase) were consistent with RNA-seq results. SMU_1315c-1317c (SMU_1315c transport-related gene) and SMU_1908c-1909c were, respectively, downregulated and upregulated in the antagonistic group. The expression patterns of adjacent genes were closely related, with correlation coefficient values greater than 0.9. These data reveal new targets (SMU_137-140, SMU_1315c-1317c, and SMU_1908c-1909c) for investigating the critical gene clusters against S. gordonii in S. mutans clinical isolates.

ß2-Microglobulin is a Novel and Reliable Biomarker for Predicting Ischemic Stroke Recurrence: A Prospective Cohort Study.

Immune and inflammatory mechanisms play key roles in the development and outcome of acute ischemic stroke (AIS). ß2-Microglobulin (ß2M) is the light chain of major histocompatibility complex-1 (MHC-1), which can directly and quickly reflect the immune and inflammatory state of the body. Previous studies have shown a close relationship between ß2M and AIS, but its relationship with the recurrence of AIS has not been reported. This study attempted to explore the relationship between ß2M and the recurrence of AIS. A single-center AIS cohort involving 135 patients was followed for approximately 26-46 months. Clinical and laboratory data from the patients were collected when hospitalized. The endpoint was the occurrence of recurrent AIS after patients were discharged. Propensity score matching was used to match cohort groups. Cox regression analysis was used to predict risk factors for recurrent AIS, and receiver operating characteristic curve (ROC) analysis was used to calculate the optimal cutoff value for discriminating recurrence in patients with AIS. The rate of recurrence was 29.6% [95% CI, 21.8%-37.3%] in the follow-up group. Patients with higher levels of serum ß2M had a higher risk of AIS recurrence than patients with lower levels of ß2M (adjusted hazard ratio, 3.214 [95% CI, 1.557-6.633]; adjusted hazard ratio after matching, 5.831, [95% CI, 2.052-16.572]). A ß2M value of 2.31 mg/L was calculated by ROC analysis as the optimal cutoff value for AIS recurrence (area under the curve 0.770, [95% CI, 0.687-0.853]). As a quick responder to the body's immune and inflammatory states, ß2M may be a novel and reliable biomarker in predicting AIS recurrence.

Design and Initial Validation of a Humanistic Care Evaluation Tool.

OBJECTIVE: This study aimed at developing and validating a humanistic care tool in Anhui province that could be used across Chinese public hospitals, and to reflect the humanistic care from patients' perspective. PARTICIPANTS: A cross-sectional survey was conducted in three public hospitals of Anhui Province, China by adopting simple random sampling, which included 312 outpatients and 323 inpatients. METHODS: The dimensions of the tool were set according to "Further Improve Medical Service Action Plan" in China and Patient-Doctor Relationship Questionnaire. Cronbach's alpha values were calculated and used to evaluate the reliability of this tool. Construct validity was tested by the exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). The associations between characteristics and humanistic care were analyzed by binary logistic regression. RESULTS: These initial findings showed that about two-thirds of the respondents experienced humanistic care. Both the reliability and construct validity of the humanistic care evaluation tool were suitable Social aspects (location and yearly income), treatment style and having a regular doctor were significantly associated with better humanistic care (all P<0.05). CONCLUSION: The humanistic care tool can directly reflect the humanistic care from patients' perspective, and can be popularized and applied across Chinese public hospitals. These findings have important implications to further improve medical service in Chinese public hospitals.

Phenotypic and genetic characteristics of Streptococcus mutans isolates from site-specific dental plaque in China.

Introduction. Streptococcus mutans is an important cariogenic microbe.Hypothesis/Gap Statement. The potential characteristics of S. mutans isolates from site-specific dental plaque are still not clear.Aim. This study aimed to investigate the phenotypic and genetic characteristics of S. mutans isolates from site-specific dental plaque in China.Methodology. We used S. mutans isolated from children with early-childhood caries (ECC) and caries-free children to compare the phenotypic and genetic characteristics of S. mutans from site-specific dental plaque samples. The ECC subjects presented two sites: a cavitated lesion and a sound surface. The caries-free subjects presented one sound surface. Growth pattern, biofilm, decrease in pH, extracellular polysaccharide, expression levels of virulence-related genes, multilocus sequence typing (MLST) and phylogenetic trees were evaluated among these three sites.Results. The phenotypes detected between the cavitated and sound surfaces of ECC children were similar. However, the capacity for biofilm formation, pH drop and expression levels of genes (gtfB and spaP) of S. mutans in the caries-free group were lower compared with those of the ECC group. We identified 44 new alleles and 77 new sequence types. More than 90 % of the children with ECC shared an identical sequence type. The distribution of sequence types among different subjects showed diversity, and child-to-child transmission was detected.Conclusions. This is the first report of MLST on site-specific dental plaques in a single subject, and indicates that S. mutans isolated from site-specific dental plaque of a single subject showed similar phenotypes as a result of the isolates were closely related.

Neutrophil-to-Lymphocyte Ratios Are Closely Associated With the Severity and Course of Non-mild COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is spreading worldwide. Measuring the prevention and control of the disease has become a matter requiring urgent focus. Objective: Based on coronavirus disease 2019 (COVID-19) clinical data from Wuhan, we conducted an in-depth analysis to clarify some of the pathological mechanisms of the disease and identify simple measures to predict its severity early on. Methods: A total of 230 patients with non-mild COVID-19 were recruited, and information on their clinical characteristics, inflammatory cytokines, and T lymphocyte subsets was collected. Risk factors for severity were analyzed by binary logistic regression, and the associations of neutrophil-to-lymphocyte ratios (N/LRs) with illness severity, disease course, CT grading, inflammatory cytokines, and T lymphocyte subsets were evaluated. Results: Our results showed that the N/LRs were closely related to interleukin (IL)-6 and IL-10 (P < 0.001, P = 0.024) and to CD3+ and CD8+ T lymphocytes (P < 0.001, P = 0.046). In particular, the N/LRs were positively correlated with the severity and course of the disease (P = 0.021, P < 0.001). Compared to the values at the first test after admission, IL-6 and IL-10 were significantly decreased and increased, respectively, as of the last test before discharge (P = 0.006, P < 0.001). More importantly, through binary logistic regression, we found that male sex, underlying diseases (such as cardiovascular disease), pulse, and N/LRs were all closely related to the severity of the disease (P = 0.004, P = 0.012, P = 0.013, P = 0.028). Conclusions: As a quick and convenient marker of inflammation, N/LRs may predict the disease course and severity level of non-mild COVID-19; male sex, cardiovascular disease, and pulse are also risk factors for the severity of non-mild COVID-19.

Serum beta2-microglobulin levels are highly associated with the risk of acute ischemic stroke.

Inflammation is considered an important mechanism of cell death or survival after ischemic stroke. As an important marker of inflammation, the role of ß2-microglobulin (ß2M) in acute ischemic stroke is unclear. We investigated the relationship between serum ß2M and the risk of acute ischemic stroke (AIS). Patients with AIS (202 cases), intracerebral hemorrhage (ICH, 41 cases), and healthy controls (253 cases) were recruited. Clinical and biochemical characteristics were collected. We used three binary logistic regression models to evaluate the correlation of ß2M with the risk of AIS. Furthermore, we investigated the relationship between serum ß2M and the National Institute of Health Stroke Scale (NIHSS) score, the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtypes, and the Essen Stroke Risk Score (ESRS) in patients with AIS. Our results showed that serum ß2M levels in patients with AIS were much higher than those in patients with ICH and in the control subjects. Individuals with higher levels of ß2M had higher odds of AIS. Moreover, serum ß2M levels were significantly and positively correlated with ESRS. In addition, the levels of ß2M were varied with different subgroups of AIS (TOAST classification). Serum ß2M is highly associated with the risk of AIS.

Serum ß2-Microglobulin Is Closely Associated With the Recurrence Risk and 3-Month Outcome of Acute Ischemic Stroke.

Background and Purpose: Inflammation plays a significant role in the pathogenesis of acute ischemic stroke (AIS). The role of ß2-microglobulin (ß2M) as a potential initiator of the inflammatory response in AIS is unclear. The purpose of this study was to analyze the relationship of serum ß2M with the recurrence risk and 3-month outcome of AIS. Methods: A total of 205 patients with AIS were recruited, and their clinical and biochemical characteristics were collected. All patients were followed up for 3 months after stroke onset, and the occurrence of death or major disability at 3 months after onset was the outcome of interest in this study. We evaluated the association of serum ß2M levels with the National Institute of Health Stroke Scale (NIHSS) scores, modified Rankin Scale (mRS) scores, and Essen Stroke Risk Score (ESRS) values in patients with AIS. Then, we used receiver operating curve analysis to calculate the optimal cutoff value for discriminating outcomes in patients with AIS and a binary logistic regression model to evaluate the risk factors for a poor outcome after AIS. Results: Our results showed that serum ß2M levels were significantly and positively correlated with ESRS values (r = 0.176, P < 0.001) and mRS scores (r = 0.402, P < 0.001), but the levels of ß2M were not correlated with NIHSS scores (r = 0.080, P = 0.255) or with infarct volume (r = 0.013, P = 0.859). In a further study, we found that 121 patients (59.02%) had poor outcomes. The optimal ß2M cutoff to predict the 3-month outcome of AIS in this study was 1.865 mg/l, and ß2M was independently associated with a poor outcome at 3 months (OR = 3.325, 95% confidence interval: 1.089~10.148). Conclusions: In conclusion, we inferred that serum ß2M was positively associated with the recurrence risk and 3-month outcome of AIS, but it did not appear to be directly related to the severity of AIS or the size of the infarct at admission.

Neutrophil-To-Lymphocyte Ratio Predicts 3-Month Outcome of Acute Ischemic Stroke.

Increasing evidences have demonstrated that inflammation is involved in the mechanisms of acute ischemic stroke (AIS). As an important and easy-to-measure inflammatory marker, neutrophil-to-lymphocyte ratio (NLR) shows a high association with mortality in patients with stroke in recent studies. In this study, we evaluated the prognostic role of NLR in patients with AIS. One hundred forty-three patients with AIS were enrolled. Clinical data were collected and the NLR was calculated from the admission blood work. The patients were followed up for 3 months after stroke onset. The occurrence of death and the major disability at 3 months after onset were end points in this study. Modified Rankin Scale score ≥3 was considered as poor outcome. In this study, 75 patients (52%) had poor outcome. We used binary logistic regression model to evaluate risk factor for poor outcome of AIS and found that the NLR was independently associated with the poor outcome of 3 months (P < 0.001). The optimal cutoff value for NLR as a predictor for 3-month outcome was 2.995. Therefore, in our study, high NLRs inversely predicted 3-month outcome in patients with AIS.

[Toxicity and oxidative stress on rats by hexachlorobenzene].

OBJECTIVE: To study the toxicity on rats by hexachlorobenzene (HCB), and to explore the role of oxidative stress in the mechanism of HCB intoxication. METHODS: SD female rats were fed on a powdered diet containing 0.25 per thousand or 2.00 per thousand HCB for 14 days. The content of malondialdehyde (MDA) and the activity of total-superoxide dismutase (T-SOD), catalase (CAT) and glutathione peroxidase (GSH-PX) in cerebral cortex, hippocampus, liver tissue and serum were determined. Eleven biochemical indicators including alkaline phosphatase (ALP) were surveyed. RESULTS: (1) MDA levels in cerebral cortex, hippocampus, liver and serum of the high dosage group rats and that in hippocampus and serum of the low dosage group were significantly higher than that of the control group. (2) The activity of T-SOD was increased in cerebral cortex and hippocampus of the rats in both groups (P < 0.01), but decreased in the serum of the high dosage group (P < 0.01). (3) The activity of CAT was also increased in the hippocampus of rats in the high dosage group. (4) In cerebral cortex and hippocampus of the rats in the high dosage group and in the hippocampus of the rats in the low dosage group, the activity of GSH-PX was significantly higher compared with the control group. However, in liver of both dosage groups, the activity of GSH-PX was decreased (P < 0.01). (5) The activity of serum alkaline phosphatase of both dosage groups was also decreased, but the contents of both serum albumin and total cholesterol were significantly higher than those of the control group (P < 0.01). CONCLUSION: HCB can induce enhanced lipid peroxidation on SD rats, and the oxidative stress plays an important role in the mechanism of neurotoxicity and hepatotoxicity.

A systematic review of social capital and chronic non-communicable diseases.

Nowadays, chronic non-communicable diseases have become a significant social problem of healthcare which threatens human health along with their rapid progress of morbidity and mortality. How to develop potential, intangible resources to compensate for insufficient physical resources is urgent. By analyzing literature reporting the association between social capital and chronic non-communicable diseases systematically, evidence was found for a positive association between social capital and chronic non-communicable disease prevention and control. The social capital theory may provide a new idea to solve the problem.