Preclinical studies show that GABA exerts anti-diabetic effects in rodent models of type 1 diabetes. Because little is known about its absorption and effects in humans, we investigated the ...pharmacokinetics and pharmacodynamics of GABA in healthy volunteers. Twelve subjects were subjected to an open-labeled, three-period trial involving sequential oral administration of placebo, 2 g GABA once, and 2 g GABA three times/day for 7 days, with a 7-day washout between each period. GABA was rapidly absorbed (Tmax: 0.5 ~ 1 h) with the half-life (t1/2) of 5 h. No accumulation was observed after repeated oral GABA administration for 7 days. Remarkably, GABA significantly increased circulating insulin levels in the subjects under either fasting (1.6-fold, single dose; 2.0-fold, repeated dose; p < 0.01) or fed conditions (1.4-fold, single dose; 1.6-fold, repeated dose; p < 0.01). GABA also increased glucagon levels only under fasting conditions (1.3-fold, single dose, p < 0.05; 1.5-fold, repeated dose, p < 0.01). However, there were no significant differences in the insulin-to-glucagon ratio and no significant change in glucose levels in these healthy subjects during the study period. Importantly, GABA significantly decreased glycated albumin levels in the repeated dosing period. Subjects with repeated dosing showed an elevated incidence of minor adverse events in comparison to placebo or the single dosing period, most notably transient discomforts such as dizziness and sore throat. However, there were no serious adverse events observed throughout the study. Our data show that GABA is rapidly absorbed and tolerated in human beings; its endocrine effects, exemplified by increasing islet hormonal secretion, suggest potential therapeutic benefits for diabetes.
Background:
Traditional Chinese medicine (TCM) is widely integrated into cancer care in China. An overview in 2011 identified 2384 randomized and non-randomized controlled trials (RCTs, non-RCTs) on ...TCM for cancer published in the Chinese literature. This article summarizes updated evidence of RCTs on TCM for cancer care.
Methods:
We searched 4 main Chinese databases: China National Knowledge Infrastructure, Chinese Scientific Journal Database, SinoMed, and Wanfang. RCTs on TCM used in cancer care were analyzed in this bibliometric study.
Results:
Of 5834 RCTs (477 157 cancer patients), only 62 RCTs were indexed in MEDLINE. The top 3 cancers treated were lung, stomach, and breast cancer. About 4752 RCTs (81.45%) tested TCM combined with conventional treatment, and 1082 RCTs (18.55%) used TCM alone for treating symptoms and side-effects. Herbal medicine was the most frequently used TCM modality (5087 RCTs; 87.20%). The most frequently reported outcome was symptom improvement (3712 RCTs; 63.63%) followed by quality of life (2725 RCTs; 46.71%), and biomarkers (2384 RCTs; 40.86%). The majority of RCTs (4051; 69.44%) concluded there were beneficial effects using either TCM alone or TCM plus conventional treatment compared with conventional treatment.
Conclusion:
Substantial randomized trials demonstrated different types/stages of cancer were treated by various TCM modalities, alone or in combination with conventional medicine. Further evaluation on the effects and safety of TCM modalities focusing on outcomes such as quality of life is required.
Gastric cancer continues to be a significant health concern in China, with a high incidence rate. To mitigate its impact, early detection and treatment is key. However, conducting large-scale ...endoscopic gastric cancer screening is not feasible in China. Instead, a more appropriate approach would be to initially screen high-risk groups and follow up with endoscopic testing as needed. We conducted a study on 25,622 asymptomatic participants aged 45–70 years from a free gastric cancer screening program in the Taizhou city government's Minimum Living Guarantee Crowd (MLGC) initiative. Participants completed questionnaires, blood tests, and underwent gastrin-17 (G-17), pepsinogen I and II (PGI and PGII), and H. pylori IgG antibody (IgG) assessments. Using the light gradient boosting machine (lightGBM) algorithm, we developed a predictive model for gastric cancer risk. In the full model, F1 score was 2.66%, precision was 1.36%, and recall was 58.14%. In the high-risk model, F1 score was 2.51%, precision was 1.27%, and recall was 94.55%. Excluding IgG, the F1 score was 2.73%, precision was 1.40%, and recall was 68.62%. We conclude that H. pylori IgG appears to be able to be excluded from the prediction model without significantly affecting its performance, which is important from a health economic point of view. It suggests that screening indicators can be optimized, and expenditures reduced. These findings can have important implications for policymakers, as we can focus resources on other important aspects of gastric cancer prevention and control.
•Early detection and treatment are crucial for gastric cancer control in China.•LightGBM, a machine learning model, optimizes gastric cancer screening for high-risk groups.•Excluding H. pylori IgG doesn't affect LightGBM's performance, saving screening costs.•Adopting cost-effective LightGBM-based strategies can enhance gastric cancer prevention.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The combination of a surface acoustic wave (SAW) biosensor with graphene oxide (GO) provides a promising perspective for detecting DNA mutation. The GO-modified SAW biosensor was prepared by ...conjugating GO onto the SAW chip surface via electrostatic interaction. Afterward, the probe was immobilized on the GO surface, and detection of DNA mutation was realized by hybridization. The hybridization with a variety of targets would yield different mass and conformational changes on the chip surface, causing the different SAW signals in real time. A total of 137 clinical samples were detected by a single-shot analytical assay based on GO-modified SAW biosensor and direct sequencing in parallel. The diagnostic performance (both sensitivity and specificity) of the assay was evaluated with the direct sequencing as a reference testing method. The phase-shift value of three genotypes in 137 clinical samples was significantly different (p < 0.001). Furthermore, testing of diagnostic performance yielded diagnostic sensitivity and specificity of 100% and 88.6% for identifying CT and CC genotype, 98.0% and 96.2% for identifying CT and TT genotype, respectively. The single-shot analytical assay based on the GO-modified SAW biosensor could be exploited as a potential useful tool to identify CYP2D6*10 polymorphisms in clinical practice of personalized medicine.
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IJS, KILJ, NUK, PNG, UL, UM
Abstract Schisantherin A (STA) is a main bioactive lignan isolated from Schisandra chinensis (Turcz.) Baill., which has been widely used as a tonic in traditional Chinese medicine for many years. ...Lots of studies have reported that STA exhibited anti-inflammatory and antioxidant effects. This paper was designed to investigate the effects of STA on cognitive function and neurodegeneration in the mouse control of Alzheimer's disease (AD) induced by Aβ1–42 . It was found that successive intracerebroventricular (ICV) administration of STA (0.01 and 0.1 mg/kg) for 5 days significantly attenuated Aβ1–42 -induced learning and memory impairment as measured by the Y-maze test, shuttle-box test and Morris water maze test. Furthermore, STA at a dose of 0.1 mg/kg restored the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) as well as the levels of Aβ1–42 , malondialdehyde (MDA) and glutathione (GSH) to some extent in the hippocampus and cerebral cortex. It also noticeably improved the histopathological changes in the hippocampus. The results suggested that STA might protect against cognitive deficits, oxidative stress and neurodegeneration induced by Aβ1–42 , and serve as a potential agent in treatment of AD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The fruits of Schisandra chinensis have been recorded as an effective somnificant for the treatment of insomnia in some oriental countries pharmacopoeias. However, the mechanism of sedative and ...hypnotic effects of this kind of herb is still unclear. In the present study, schizandrin, which is the main component of Schisandra chinensis, was selected as a target compound to investigate possible mechanisms through behavioral pharmacology methods. The results showed that schizandrin possessed dose-dependent (5–45mg/kg, i.p.) sedative effects on locomotion activity in normal mice, and produced a dose-dependent decrease in sleep latency and an increase in sleep duration in pentobarbital-treated mice; thus, itself did not induce sleep at higher dose which was used in this experiment (45mg/kg, i.p.). It also can reverse the rodent models of insomnia induced by p-chlorophenylalanine (PCPA) and caffeine, which could exhibit a synewith 5-hydroxytryptophan (5-HTP) as well; therefore, the hypnotic effects of schizandrin were not inhibited by flumazenil (a specific gamma aminobutyric acid (GABA)-A-BZD receptor antagonist). Altogether, these results indicated that schizandrin produces beneficial sedative and hypnotic bioactivity, which might be mediated by the modification of the serotonergic system.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Objective To compare the curative effect of intravitreal injection of triamcinolone acetonide and aflibercept on diabetic retinopathy (DR) cystoid macular edema. Methods A total of 102 patients with ...DR cystoid macular edema admitted to the hospital were enrolled between July 2018 and July 2021. According to random number table method, they were divided into the control group (intravitreal injection of triamcinolone acetonide) and the observation group (intravitreal injection of aflibercept), 51 cases in each group. All were followed up for half a year. The clinical curative effect, visual acuity, central subfield macular thickness (CSMT), macular volume, scores of quality of life, and levels of cytokines in aqueous humor (vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), human angiopoietin-like protein 4 (ANGPTL4) at different time points (before and at 6 months after surgery) were compared between the two groups. The times of drugs injection and occurrence of adverse reactions in both groups were statistically analyzed. Results The total effective rate in observation group was higher than that in the control group (96.08% vs 82.35%) (P<0.05). After 6 months of treatment, visual acuity was improved, and CSMT and macular volume were decreased in both groups. Also, the above changes were more significant in the observation group than those in the control group (P<0.05). After 6 months of treatment, levels of cytokines in aqueous humor were decreased in both groups. The levels of VEGF, MCP-1, and ANGPTL4 in observation group were lower than those in the control group (P<0.05). After 6 months of treatment, quality of life scores in observation group were higher than those in the control group (P<0.05). In the follow-up period, average times of drugs injection in the observation group were more than those in the control group, and the incidence of adverse reactions was lower than that in control group (5.88% vs 21.57%) (P<0.05). Conclusion The curative effect of intravitreal injection of both triamcinolone acetonide and aflibercept is good on DR cystoid macular edema. The curative effect of aflibercept is better, which can improve visual acuity and quality of life, and regulate cytokines in aqueous humor, with high safety. However, aflibercept has a high price, and further research is needed to determine whether its price can be matched with clinical benefits. In clinic, medication plan should be selected according to the actual situation.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Thyroid cancer (TC) is one of the most commonly seen secondary malignancy in breast cancer (BC) survivors.
Materials and methods
A retrospective study was conducted in BC patients in our ...center from 1999 to 2013. Patients were divided into BC‐TC group and BC‐alone group.
Results
In total, 13 978 BC patients were identified, among whom 247 (1.8%) had TC. The standardized incidence ratio (SIR) of TC was 4.48 compared with Chinese females, and up to 98.0% of cases were thyroid papillary carcinomas. A family history of malignancy was the only independent risk factor (odds ratio = 1.457, P = 0.025) for development of TC in patients with BC. We also identified inferior survival in patients with synchronous versus metachronous BC‐TC (P = 0.016). Synchronous BC‐TC (risk ratio = 5.597, P = 0.018) was an independent prognostic factor for inferior RFS.
Conclusions
We observed high co‐occurrence of TC in patients with BC. There might be different mechanisms behind synchronous and metachronous BC‐TC.
In the current study, we investigated the association of thyroid cancer incidence in a cohort of 13 978 breast cancer patients. We identified that the standardized incidence ratio of secondary thyroid cancer was significantly increased and a family history of malignancy was the only independent risk factor, which provided a new insight into the association of breast cancer and thyroid cancer.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Dry eye disease (DED) is a prevalent ocular disorder with a multifactorial etiology. The pre-angiogenic and pre-inflammatory milieu of the ocular surface plays a critical role in its pathogenesis. ...DZ2002 is a reversible type III S-adenosyl-L-homocysteine hydrolase (SAHH) inhibitor, which has shown excellent anti-inflammatory and immunosuppressive activities in vivo and in vitro. In this study, we evaluated the therapeutic potential of DZ2002 in rodent models of DED. SCOP-induced dry eye models were established in female rats and mice, while BAC-induced dry eye model was established in female rats. DZ2002 was administered as eye drops (0.25%, 1%) four times daily (20 μL per eye) for 7 or 14 consecutive days. We showed that topical application of DZ2002 concentration-dependently reduced corneal neovascularization and corneal opacity, as well as alleviated conjunctival irritation in both DED models. Furthermore, we observed that DZ2002 treatment decreased the expression of genes associated with angiogenesis and the levels of inflammation in the cornea and conjunctiva. Moreover, DZ2002 treatment in the BAC-induced DED model abolished the activation of the STAT3-PI3K-Akt-NF-κB pathways in corneal tissues. We also found that DZ2002 significantly inhibited the proliferation, migration, and tube formation of human umbilical endothelial cells (HUVECs) while downregulating the activation of the STAT3-PI3K-Akt-NF-κB pathway. These results suggest that DZ2002 exerts a therapeutic effect on corneal angiogenesis in DED, potentially by preventing the upregulation of the STAT3-PI3K-Akt-NF-κB pathways. Collectively, DZ2002 is a promising candidate for ophthalmic therapy, particularly in treating DED.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This study aims to summarize the clinical characteristics of one teenager with autoimmune polyglandular syndrome (APS) type III C + D to improve the understanding of APS III C + D and its effect of ...thyroid function.
This article reported the clinical manifestations, laboratory examinations, treatment methods, and outcomes of an adolescent with anemia admitted to the Pediatrics Department of Tianjin Medical University General Hospital in July 2020 and reviewed the literature.
A girl, aged 13 years and 1 month, was admitted to the hospital due to anemia for more than 4 years and episodic abdominal pain for 1 week. Four years ago, the girl went to a local hospital for "vitiligo", and a routine blood test revealed anemia. The lowest hemoglobin (HGB) was 61 g/L, and the blood test revealed iron deficiency anemia. She had no menstrual cramps for 2 months. Urine routine showed protein 3+∼4+ and 258 red blood cells (RBCs)/high-power field. Urine protein was 3,380 mg/24 h. Free thyroxine was low, thyroid-stimulating hormone was >100 uIU/ml, thyroid peroxidase antibody was >1,000 IU/ml, and thyroglobulin antibody and thyrotropin receptor antibody were negative. Pituitary magnetic resonance imaging showed a mass in the sellar region with a uniform signal and a maximum height of about 15.8 mm. The result of the antinuclear antibody was 1:80 homogeneous type, and anti-dsDNA and anticardiolipin antibodies IgA and IgM were slightly higher. Thyroxine and iron were given for 1 month, menstruation resumed, and urine protein and RBC count decreased. After 5 months of treatment, free thyroid function, HGB, RBCs in urine, and pituitary returned to normal. Later, a renal biopsy showed changes in focal proliferative glomerulonephritis, and the girl was diagnosed with lupus glomerulonephritis type III. After 3 days of shock therapy with methylprednisolone, prednisone, mycophenolate mofetil, and other treatments were administrated for 1 year. At the time of writing, urine protein was 280 mg/24 h.
Co-occurrence of Hashimoto's thyroiditis, vitiligo, anemia, pituitary hyperplasia, and lupus nephritis is rare. It is very important to pay attention to the screening of thyroid function.