Pan-cancer analyses reveal the molecular and clinical characteristics of TET family members and suggests that TET3 maybe a potential therapeutic target.

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors.

BACKGROUND: The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM: To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS: Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS: Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION: Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Vincristine exposure impairs mouse oocyte quality by inducing spindle defects and early apoptosis.

Vincristine (VCR) is a microtubule-destabilizing chemotherapeutic agent commonly administered for the treatment of cancers in patients, which can induce severe side effects including neurotoxicity. In context of the effects on female fertility, ovarian toxicity has been found in patients and mice model after VCR exposure. However, the influence of VCR exposure on oocyte quality has not been elucidated. We established VCR exposure in vitro and in vivo model. The results indicated in vitro VCR exposure contributed to failure of oocyte maturation through inducing defects in spindle assembly, activation of SAC, oxidative stress, mitochondrial dysfunction, and early apoptosis, which were confirmed by using in vivo exposure model. Moreover, in vivo VCR exposure caused aneuploidy, reduced oocyte-sperm binding ability, and the number of cortical granules in mouse oocyte cortex. Taken together, this study demonstrated that VCR could cause meiotic arrest and poor quality of mouse oocyte.

Flexible solar cells based on foldable silicon wafers with blunted edges.

Flexible solar cells have a lot of market potential for application in photovoltaics integrated into buildings and wearable electronics because they are lightweight, shockproof and self-powered. Silicon solar cells have been successfully used in large power plants. However, despite the efforts made for more than 50 years, there has been no notable progress in the development of flexible silicon solar cells because of their rigidity1-4. Here we provide a strategy for fabricating large-scale, foldable silicon wafers and manufacturing flexible solar cells. A textured crystalline silicon wafer always starts to crack at the sharp channels between surface pyramids in the marginal region of the wafer. This fact enabled us to improve the flexibility of silicon wafers by blunting the pyramidal structure in the marginal regions. This edge-blunting technique enables commercial production of large-scale (>240 cm2), high-efficiency (>24%) silicon solar cells that can be rolled similarly to a sheet of paper. The cells retain 100% of their power conversion efficiency after 1,000 side-to-side bending cycles. After being assembled into large (>10,000 cm2) flexible modules, these cells retain 99.62% of their power after thermal cycling between -70 °C and 85 °C for 120 h. Furthermore, they retain 96.03% of their power after 20 min of exposure to air flow when attached to a soft gasbag, which models wind blowing during a violent storm.

Novel hypoxia-related gene signature for predicting prognoses that correlate with the tumor immune microenvironment in NSCLC.

Background: Intratumoral hypoxia is widely associated with the development of malignancy, treatment resistance, and worse prognoses. The global influence of hypoxia-related genes (HRGs) on prognostic significance, tumor microenvironment characteristics, and therapeutic response is unclear in patients with non-small cell lung cancer (NSCLC). Method: RNA-seq and clinical data for NSCLC patients were derived from The Cancer Genome Atlas (TCGA) database, and a group of HRGs was obtained from the MSigDB. The differentially expressed HRGs were determined using the limma package; prognostic HRGs were identified via univariate Cox regression. Using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression, an optimized prognostic model consisting of nine HRGs was constructed. The prognostic model's capacity was evaluated by Kaplan‒Meier survival curve analysis and receiver operating characteristic (ROC) curve analysis in the TCGA (training set) and GEO (validation set) cohorts. Moreover, a potential biological pathway and immune infiltration differences were explained. Results: A prognostic model containing nine HRGs (STC2, ALDOA, MIF, LDHA, EXT1, PGM2, ENO3, INHA, and RORA) was developed. NSCLC patients were separated into two risk categories according to the risk score generated by the hypoxia model. The model-based risk score had better predictive power than the clinicopathological method. Patients in the high-risk category had poor recurrence-free survival in the TCGA (HR: 1.426; 95% CI: 0.997-2.042; p = 0.046) and GEO (HR: 2.4; 95% CI: 1.7-3.2; p < 0.0001) cohorts. The overall survival of the high-risk category was also inferior to that of the low-risk category in the TCGA (HR: 1.8; 95% CI: 1.5-2.2; p < 0.0001) and GEO (HR: 1.8; 95% CI: 1.4-2.3; p < 0.0001) cohorts. Additionally, we discovered a notable distinction in the enrichment of immune-related pathways, immune cell abundance, and immune checkpoint gene expression between the two subcategories. Conclusion: The proposed 9-HRG signature is a promising indicator for predicting NSCLC patient prognosis and may be potentially applicable in checkpoint therapy efficiency prediction.

The Relieving Effects of a Polyherb-Based Dietary Supplement ColonVita on Gastrointestinal Quality of Life Index (GIQLI) in Older Adults with Chronic Gastrointestinal Symptoms Are Influenced by Age and Cardiovascular Disease: A 12-Week Randomized Placebo-Controlled Trial.

Chronic gastrointestinal symptoms (CGS) negatively affect the quality of life in about 15-30% of the population without effective drugs. Recent studies suggest that dietary supplement may improve CGS, but inconsistent results exist. The goal of this study is to evaluate the effect of a polyherbal-based supplement ColonVita on the gastrointestinal quality of life index (GIQLI) in 100 old adults with CGS (63.1 ± 9.6 years) who were randomly assigned to daily ColonVita or placebo tablets (n = 50/group) for 12 weeks in a double-blind, randomized controlled trial design. No significant fibrdifferences were found between ColonVita and placebo in the baseline total GIQLI score (101.12 ± 16.87 vs. 101.80 ± 16.48) (P > 0.05) or postintervention total GIQLI score (114.78 ± 9.62 vs. 111.74 ± 13.01) (P > 0.05). However, ColonVita significantly improved 16 scores of the 19 core GI symptoms compared with 10 items improved by placebo. The ColonVita group significantly improved the remission rate of 5 core GI symptoms compared to placebo and significantly improved the total GIQLI scores (118.09 ± 7.88 vs. 109.50 ± 16.71) (P < 0.05) and core GI symptom scores (64.61 ± 3.99 vs. 60.00 ± 8.65) (P < 0.05) in people ≥60 years of age (n = 49) but not in those under 60 y (n = 51). ColonVita significantly improved the total GIQLI scores and core GI symptom scores in people without cardiovascular diseases (CVD) (n = 56) (116.74 ± 9.38 vs. 110.10 ± 14.28) (P < 0.05) and (63.11 ± 4.53 vs. 59.93 ± 8.03) (P=0.07), respectively, but not in those with CVD (n = 44). Thus, ColonVita was beneficial for old adults with CGS, especially those ≥60 years of age and without CVD. Because a heterogenous pathogenesis of CGS-like irritable bowel syndrome (IBS) and inflammatory bowel disease (ISD) is differentially associated with CVD, different comorbidities may have influenced the outcomes of different trials that should be controlled in further studies.

Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury.

Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been identified, its relationship with altered expression of neurodegenerative proteins has not been examined before. This study aimed to investigate 1) how TBI could affect mitochondrial ETC and neurodegeneration in rat brain regions related to behavioral alteration, and 2) if administration of the key mitochondrial substrate pyruvate can improve the outcome of mild TBI (mTBI). In a rat lateral fluid percussion injury model of mTBI, sodium pyruvate in sterile distilled water (1 g/kg body weight) was administered orally daily for 7 days. The protein expression of mitochondrial ETC enzymes, and neurodegeneration proteins in the hippocampus and cerebral cortex and was assessed on Day 7. The hippocampal and cortical expressions of ETC complex I, III, IV, V were significantly and variably impaired following mTBI. Pyruvate treatment altered ETC complex expression, reduced the nitrosyl stress and the MBP expression in the injured brain area, but increased the expression of the glial fibrillary acidic protein (GFAP) and Tau proteins. Pyruvate after mTBI augmented the Rotarod performance but decreased the horizontal and vertical open field locomotion activities and worsened neurobehavioural severity score, indicating a debilitating therapeutic effect on the acute phase of mTBI. These results suggest bidirectional neuroprotective and neurodegenerative modulating effects of pyruvate on TBI-induced alteration in mitochondrial activity and motor behavior. Pyruvate could potentially stimulate the proliferation of astrogliosis, and lactate acidosis, and caution should be exercised when used as a therapy in the acute phase of mTBI. More effective interventions targeted at multiple mechanisms are needed for the prevention and treatment of TBI-induced long-term neurodegeneration.

Effects of Yunanan Baiyao adjunct therapy on postoperative recovery and clinical prognosis of patients with traumatic brain injury: A randomized controlled trial.

BACKGROUND: Effective therapies are needed to prevent the secondary injury and poor prognosis associated with emergency craniotomy of traumatic brain injury (TBI). HYPOTHESIS/PURPOSE: The wound-healing medicine Yunnan Baiyao (YB) and Xingnaojing (XNJ) adjunct-therapy may improve the outcome of orthodox mono-therapy (OT). STUDY DESIGN: Randomized controlled trial. METHODS: Eighty patients with moderate-to-severe TBI received emergency craniotomy (within 12 h after TBI) at the Chinese PLA General Hospital before being randomly assigned to 4 different treatments (n = 20) for 7 days: 1) OT; 2) OT+XNJ (i.v. 20 ml/daily); 3) OT+low dose-YB (oral, 1,000 mg/day); 4) OT+high dose-YB, 2,000 mg/day). RESULTS: GCS score was improved more quickly and became significantly higher in XNJ, l-YB, h-YB groups than in OT group (p<0.01). Serum S100B peaked higher but declined more slowly in OT group than in other groups (p<0.01). On postoperative Day 7, S100B was 20% below baseline in YB and XNJ groups but remained 19% above baseline in OT group which also lost 38% of superoxide dismutase (SOD) activity on Day 3 and recovered 69% of SOD on Day 7 whereas the YB and XNJ groups lost 16%∼23% of SOD activity on Day 3 and recovered 92%∼99% of SOD on Day 7 (p<0.01). Clinical prognosis (Glasgow Outcome Scale and Karnofsky Performance Scale) were significantly better (25%∼30%) in the XNJ, l-YB and h-YB groups than in OT group 3 months post-surgery and were correlated with serum S100B and SOD. CONCLUSIONS: YB and XNJ adjunct therapies improved postoperative recovery and clinical prognosis in patients with moderate-to-severe TBI partly through divergent regulation of S100B and SOD pathways. (The trial was registered at Chinese Clinical Trial Registry (ChiCTR) trial registration number: ChiCTR2000030280).

Shi-Zhen-An-Shen Decoction, a Herbal Medicine That Reverses Cuprizone-Induced Demyelination and Behavioral Deficits in Mice Independent of the Neuregulin-1 Pathway.

Shi-Zhen-An-Shen decoction (SZASD), a Chinese herbal medicine that is a liquor extracted from plants by boiling, has been reported to be effective in treating schizophrenia. However, the mechanism is unclear. Abnormal demyelination has been implicated in schizophrenia. The aim of this study was to investigate the effect of SZASD on myelin in demyelinated mice exhibiting schizophrenia-like behaviors. Sixty male C57BL/6 mice were randomly divided into six groups (n = 10 per group): (1) control group, (2) cuprizone (CPZ, a copper chelator that induced demyelination, 0.2% w/w)+saline, (3) CPZ+low-dose SZASD (8.65 g·kg-1·d-1), (4) CPZ+medium-dose SZASD (17.29 g·kg-1·d-1), (5) CPZ+high-dose SZASD (25.94 g·kg-1·d-1), and (6) CPZ+quetiapine (QTP, an atypical antipsychotic that served as a positive treatment control, 10 mg·kg-1·d-1). Mice in groups 2-6 were treated with CPZ added to rodent chow for six weeks to induce demyelination. During the last two weeks, these mice were given an oral gavage of sterile saline, SZASD, or quetiapine. Behavioral tests and brain analyses were conducted after the last treatment. The brain expression of myelin basic protein (MBP) and neuregulin-1 (NRG-1) was assessed using immunohistochemistry and Western blots. CPZ induced significant schizophrenia-like behaviors in the mice, including reduced nest-building activity and sensory gating deficits. Hyperlocomotor activity was accompanied by significant reductions in MBP expression in the corpus callosum, hippocampus, and cerebral cortex. However, both QTP and SZASD significantly reversed the schizophrenia-like behaviors and demyelination in CPZ-fed mice. The QTP and medium-dose SZASD resulted in better therapeutic effects compared to the low and high SZASD doses. Reduced NRG-1 expression was observed in CPZ-fed mice compared with controls, but neither QTP nor SZASD showed significant influence on NRG-1 expression in the hippocampus. Together, SZASD showed a therapeutic effect on demyelinated mice, and the improvement of demyelination might not be through the NRG-1 pathway.

Comparison of inflammatory, nutrient, and neurohormonal indicators in patients with schizophrenia, bipolar disorder and major depressive disorder.

Psychiatric disorders are severe, debilitating conditions with unknown etiology and are commonly misdiagnosed, when based solely on clinical interviews, because of overlapping symptoms and similar familial patterns. Until now, no valid and objective biomarkers have been used to diagnose and differentiate between psychiatric disorders. We compared clinically tested serum indicators in terms of inflammation (C-reactive protein, complement proteins C3 and C4, and serum Immunoglobulins A, M, and G), nutrients (homocysteine, folate, and vitamin B12), and neurohormones (adrenocorticotropic hormone and cortisol) in patients with schizophrenia (SCZ, n = 1659), bipolar disorder (BD, n = 1901), and major depressive disorder (MDD, n = 1521) to investigate potential biomarkers. A receiver operating characteristic (ROC) curve was used to analyze the diagnostic potential of these analytes. We found that compared with MDD, serum levels of C-reactive protein, C3, C4, and homocysteine were higher in SCZ and BD groups, and folate and vitamin B12 were lower in SCZ and BD groups. In contrast with BD, adrenocorticotropic hormone and cortisol increased in patients with MDD. Although ROC analysis suggested that they were not able to effectively distinguish between the three, these biological indicators showed different patterns in the three disorders. As such, more specific biomarkers should be explored in the future.

miR-212 as potential biomarker suppresses the proliferation of gastric cancer via targeting SOX4.

BACKGROUND: Circulating microRNAs that post-transcriptionally regulate gene expressions have been reported as promising biomarkers in cancer monitoring. This study was to identify the potential role of circulating miR-212 in gastric cancer and whether it could serve as a novel biomarker for gastric cancer. METHODS: We detected the serum levels of miR-212 in 100 health people and 110 gastric cancer patients and analyzed the relationships of the serum level of miR-212 with gastric cancer. We detected the expression of miR-212 in human gastric mucosal epithelial cell line (GES-1) and human gastric cancer cell lines (NCI-N87 and SNU-16) using qRT-PCR. Then, we detected the role of 5-aza-deoxycytidine on the epigenetic regulation of miR-212 in human gastric cancer cell lines. Furthermore, luciferase reporter assay was used to detect binding activity of miR-212 on SOX4 mRNA, and their functions on the cell proliferation and apoptosis. RESULTS: The expression of miR-212 was higher in health people than that in gastric cancer patients, higher in gastric mucosal epithelial cell line than that in gastric cancer cells. miR-212 can be a circulating biomarker and an independent prognostic factor of gastric cancer. Moreover, miR-212 can directly regulate the 3'UTR of SOX4 mRNA to suppress p53 and Bax, resulting gastric cancer cells proliferation inhibition and apoptosis induction. CONCLUSION: Our study demonstrated that miR-212 was epigenetically downregulated in gastric cancer, and resulting low level of miR-212 can be a potential circulating biomarker and poor prognosis predicator of gastric cancer.

Subjective Cognitive Decline and Related Cognitive Deficits.

Since late stage dementia, including Alzheimer's disease (AD), cannot be reversed by any available drugs, there is increasing research interest in the preclinical stage of AD, i.e., subjective cognitive decline (SCD). SCD is characterized by self-perceptive cognitive decline but is difficult to detect using objective tests. At SCD stage, the cognitive deficits can be more easily reversed compared to that of mild cognitive impairment (MCI) and AD only if accurate diagnosis of SCD and early intervention can be developed. In this paper, we review the recent progress of SCD research including current assessment tools, biomarkers, neuroimaging, intervention and expected prognosis, and the potential relevance to traumatic brain injury (TBI)-induced cognitive deficits.

Playing Mahjong for 12 Weeks Improved Executive Function in Elderly People With Mild Cognitive Impairment: A Study of Implications for TBI-Induced Cognitive Deficits.

Background: Mild cognitive impairment (MCI) is common among elderly people. So far, effective treatment that can stabilize or reverse the cognitive decline associated with MCI is lacking. Recent studies suggest that playing mahjong may improve attention and memory in elderly people. However, its effect on executive function remains unknown. Methods: 56 elderly people (74.3 ± 4.3 years of age) with MCI from the First Social Welfare the First Nursing Home of Nanchong were randomized into mahjong and control groups (N = 28, each group). Subjects in the mahjong group played mahjong three times a week for 12 weeks, while people in the control group assumed normal daily activity. Executive function was evaluated using the Montreal Cognitive Assessment-Beijing (MoCA-B), the Shape Trail Test (STT), and the Functional Activities Questionnaire (FAQ) before the study and then at 6 and 12 weeks after mahjong administration. Results: There were no baseline differences in MoCA-B, STT, and FAQ scoring between the two groups. The MoCA-B, STT, and FAQ scores, however, improved significantly in the mahjong group but not in the control group after the 12-week mahjong administration. Significant correlations were also found between STT and FAQ scores. Conclusions: Playing Mahjong for 12 weeks improved the executive function of elderly people with MCI. Because Mahjong is a simple, low-cost entertainment activity, it could be widely applied to slow down or reverse the progression of cognitive decline in people with MCI, including those with traumatic brain injury.

A Clinicopathological Report of a 93-Year-Old Former Street Boxer With Coexistence of Chronic Traumatic Encephalopathy, Alzheimer's Disease, Dementia With Lewy Bodies, and Hippocampal Sclerosis With TDP-43 Pathology.

Chronic traumatic encephalopathy (CTE) was recently recognized as a new tauopathy in which multifocal perivascular phosphorylated tau aggregates accumulate in neurons, astrocytes, and neurites at the depths of the cortical sulci. Traumatic brain injury (TBI) in early or mid-life is known to be associated with an increased risk of dementia in late life. This case report describes a 93-year-old former street boxer with a premortem diagnosis of severe dementia, who showed pathological evidence of the coexistence of Alzheimer's disease, CTE, dementia with Lewy bodies, and hippocampal sclerosis with TDP-43 pathology. These findings suggest that TBI may trigger a variety of misfolded proteins leading to dementia. Currently, clear clinical diagnostic criteria for CTE have not been established. Therefore, clinicians should be aware that TBI is a risk factor for dementia and that CTE can overlap with other neurodegenerative diseases.

Association of CYP2C19 Polymorphism with Clopidogrel Resistance in Patients with Acute Coronary Syndrome in China.

BACKGROUND The relationship between clopidogrel-resistance (CR) and polymorphism located in genes encoding clopidogrel metabolism-related enzymes has not been fully explored. Thus far, few studies on CR-associated polymorphism have been conducted in the Chinese population. The purpose of this study was to identify CYP2C19 polymorphism associated with CR in patients with acute coronary syndrome in China. MATERIAL AND METHODS There were 125 patients with acute coronary syndromes (ACS) selected for this study. Of these, 27 patients (21.6%) showed CR (less than 10% reduction in platelet accumulation rate), while the remaining 98 patients (78.4%) were non-clopidogrel-resistant (NCR). RESULTS There were significant differences in the allele frequencies of CYP2C19 (rs4244285) (P=0.03) and CYP2C19 (rs4986893) (P=0.005) between the 2 groups; however, there was no significant difference in allele frequencies of ABCB1 (rs1045642) (P=0.661) and PON1 (rs662) (P=0.690) between the 2 groups. The null allele in the CYP2C19 (rs4244285) [odds ratio (OR)=5.317, 95% confidence interval (CI) 1.542-26.428, P=0.001] and CYP2C19 (rs4986893) (OR=4.295, 95%CI 1.312-17.517, P=0.013) is one of the causes of CR in patients with ACS in China. CONCLUSIONS The CYP2C19 polymorphism (rs4244285 and rs4986893) is the correlative factor of CR in patients with ACS in China. It was found that the null allele in the CYP2C19 polymorphism was related to the higher CR risk. According to the key role of CYP2C19 in the clopidogrel activation and the evaluated role of CYP2C19 in this study, further studies should be carried out to formulate therapeutic alternative methods for CR in patients with ACS.

Effects of 12-Week Supplementation of a Polyherbal Formulation in Old Adults with Prehypertension/Hypertension: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Uncontrolled blood pressure is the leading cause of mortality and disability due to associated cerebral and cardiovascular diseases and kidney failure. More than one-third of the old adult population have hypertension or prehypertension and many of their blood pressure are poorly controlled. OBJECTIVE: We hypothesized that plant extracts-based antioxidants may benefit those with prehypertension/hypertension. METHOD: One hundred age- and gender-matched healthy older adults were randomly assigned to receive HyperBalance capsules (n=50) or placebo (n=50) at Tang-Qiao Community Health Service Center, Shanghai. Blood pressure and severity scores of hypertension treatment-related symptoms (dizziness, headache, ringing/buzzing in ears, rapid heart rate, and chest tightness) were evaluated before and after the 12-week intervention. RESULTS: Ninety-eight people completed the study, with 2 dropouts in the placebo group before the end of the study. Forty-one subjects (82%) of the HyperBalance group and 40 subjects (83.3%) of the placebo group had prehypertension (systolic blood pressures (SBP) between 130-139 and diastolic blood pressure (DBP) between 85-89mmHg), and 9 subjects (18%) in the HyperBalance group and 8 subjects (16.7%) in the placebo group had hypertension (≥140/90mmHg) before the intervention. HyperBalance significantly (P<0.01) reduced SBP from 136.18±4.38 to 124.14±3.96 mmHg and reduced DBP from 82.45±2.91 to 80.24±2.41mmHg, respectively, and reversed all 9 hypertension people to normotension or prehypertension state, whereas the placebo moderately reduced SBP from 135.79±4.22 to 132.35±4.656mmHg and reduced DBP from 82.90±3.07 to 82.27±3.01mmHg. All symptom severity scores became significantly lower in the HyperBalance group than in the placebo group after HyperBalance intervention: dizziness (0.82±0.44; vs 2.02±0.64, P<0.01); headache (0.46±0.50; vs 1.81±0.61, P<0.01); ringing/buzzing in ears (0.44±0.50; vs 1.04±0.29, P<0.01); and rapid heart rate and chest tightness (0.30±0.46; vs 0.92±0.28, P<0.01). CONCLUSION: Polyherbal supplementation such as HyperBalance could benefit old adults with prehypertension/hypertension and improve treatment-related symptoms. Further studies are needed to validate the current findings.

Postprandial Glucose Levels Are Better Associated with the Risk Factors for Diabetes Compared to Fasting Glucose and Glycosylated Hemoglobin (HbA1c) Levels in Elderly Prediabetics: Beneficial Effects of Polyherbal Supplements-A Randomized, Double-Blind, Placebo Controlled Trial.

BACKGROUNDS: Prediabetes is a condition in which a person's blood glucose levels are higher than normal physiological levels but lower compared to patients with diabetes. Up to 70% of individuals with prediabetes will eventually develop diabetes. To date, there have been no pharmaceutical drugs to treat diabetes. It is believed that early diagnosis and nonpharmacological intervention for prediabetes are critical for effective prevention of diabetes. Most individuals with prediabetes remain undiagnosed even after being evaluated using the standard tests for fasting glucose (FG) and HbA1c. We investigated if postprandial glucose levels (2h-PG) were associated with pre/diabetes and if polyherbal supplements could be beneficial for individuals with prediabetes. MATERIALS AND METHODS: 100 elderly individuals with impaired 2h-PG or fasting glucose levels were recruited to receive either a 12-week supplement of GlucoVita (an antioxidative polyherbal formulation) (n=50) or placebo (n=50). RESULTS: No baseline differences were observed for FG, HbA1c, or 2h-PG. Individuals who received a twelve-week administration of GlucoVita supplements had significantly reduced 2h-PG (8.15±1.67 versus 7.35±2.06 mmol/l, P<0.05) levels compared to individuals in the placebo group. In addition, HbA1c levels were lower in individuals who received GlucoVita (5.81±0.49 %) compared to the individuals in the placebo group (6.00±0.51%) (P=0.08) after 12-weeks. Stratified analysis, based on impaired fasting glucose (IFG), 2h-PG, metabolic symptom, and age, demonstrated that, after the 12-week intervention, HbA1c levels were significantly lower in the GlucoVita administered group compared to the placebo group (IFG subgroup; 5.85±0.46%, n= 27 versus 6.14±0.50, n=33, P<0.05) and the metabolic symptom-free subgroup (5.73±0.45%, n=23 versus 6.04±0.52%, n=24, P<0.05). GlucoVita also reduced FG in individuals with normal 2h-PG (6.37±0.27 versus 6.08±0.38 mmol/l, P<0.05). Baseline 2h-PG levels, but not HbA1c or FG levels, were significantly correlated with body weight, waist circumference, and BMI (r=0.25, P<0.05; r=0.31, P<0.01; r=0.22, P<0.05, respectively). CONCLUSION: 2h-PG levels were better associated with body weight, waist circumference, and BMI risk factors compared to FG and HbA1c levels in elderly individuals with prediabetes. Polyherbal formulation GlucoVita supplements improved 2h-PG and HbA1c levels only in elderly individuals who were overweight but were symptom-free and under 65 years of age. Due to the small cohort size of this pilot study, future studies are required to validate our findings.

Effects of High-Frequency Transcranial Magnetic Stimulation for Cognitive Deficit in Schizophrenia: A Meta-Analysis.

Objective: Repetitive transcranial magnetic stimulation (rTMS) has been applied to dorsolateral prefrontal cortex (DLPFC) to improve cognitive function of patients with schizophrenia (SZs). The aim of this meta-analysis was to evaluate whether a high-frequency rTMS course could enhance cognitive function in SZs. Methods: Studies published in PubMed, Cochrane Library, Embase, ScienceDirect, and Web of science were searched until April 2018. The search terms included: "repetitive transcranial magnetic stimulation" or "Rtms," "SZ," or "schizophrenia," and "neuro-cognition" or "neurocognitive performance" or "cognitive effects" or "cognitive" or "cognition" or "working memory" or "executive function" or "language function" or "processing speed," After screening the literatures according to inclusion and exclusion criteria, extracting data, and evaluating the methodological quality of the included studies, a meta-analysis was performed using RevMan 5.3 software (The Cochrane Collaboration, USA). Results: A total of 9 studies on cognitive dysfunction of SZs were included and involved 351 patients. A significant efficacy of high-frequency rTMS on working memory in SZs was found compared to sham stimulation [p = 0.009, standardized mean difference (SMD) = 0.34]. Specifically, rTMS treatment positioned on the left DLPFC, with a total pluses <30,000 was more significantly more effective in improving the working memory (SMD = 0.33, p = 0.03). No improvement was found in other cognitive domains such as executive function, attention, processing speed, and language function. For the follow-up observations, high-frequency rTMS had long-lasting sustained effects on working memory (SMD = 0.45, p = 0.01) and language function (SMD = 0.77, p = 0.02) in SZs. Conclusions: High-frequency rTMS over the left DLPFC with a total pulses <30,000 stimulation could significantly improve working memory in SZs for an extended period of time.

Transcranial Direct Current Stimulation Improves Cognitive Function in Mild to Moderate Alzheimer Disease: A Meta-Analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the therapeutic effect of transcranial direct current stimulation (tDCS) on mild to moderate Alzheimer disease (AD) patients. MATERIALS AND METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched until April 2018. The primary cognitive outcomes were extracted from included articles. A crude standardized mean difference with 95% CI was calculated by using fixed or random effect models. RESULTS: Seven studies with 146 patients were included in this meta-analysis. The pooled result showed that tDCS significantly improved cognitive function of AD patients (standardized mean difference=0.37; 95% CI, 0.09-0.65; P=0.01). Subgroup analyses showed that: a single session of tDCS was significantly effective (P<0.05) whereas repeated sessions of tDCS was not lower current density (0.06 mA/cm) (P>0.05) but not higher current density (0.08 mA/cm) significantly improved cognitive performance; stimulating the temporal cortex (P<0.05) but not the left dorsal lateral prefrontal cortex significantly improved cognitive function of AD patients; and improved cognitive function occurred in the group with higher education (P<0.05) but not in the group with lower education. CONCLUSIONS: Current evidence suggests that tDCS has a beneficial effect in mild to moderate AD patients. We must be cautious about the results of subgroup analysis given small sample sizes, and further well-designed studies with larger sample size are required to verify these results.