Association of hypoglycemic events with cognitive impairment in patients with type 2 diabetes mellitus: Protocol for a dose-response meta-analysis.

INTRODUCTION: With an incidence rate as high as 46%-58%, hypoglycemia is a common complication of glycemic management among those suffering from type 2 diabetes mellitus(T2DM). According to preclinical research, hypoglycemia episodes may impair cognition by harming neurons. However, there is still controversy regarding the clinical evidence for the relationship between hypoglycemic events and the likelihood of cognitive impairment. Furthermore, little research has been done on the dose-response association between hypoglycemia incidents and the possibility of cognitive impairment. To address these knowledge gaps, the present research intends to update the comprehension of the association among hypoglycemic events and the risk of cognitive impairment and to clarify the correlation between dose and response by incorporating the most recent investigations. METHOD AND ANALYSIS: This work has developed a protocol for a systematic review and meta-analysis that will examine, via a well-organized assessment of several databases, the relationship between the incidence of hypoglycemia and the probability of cognitive impairment. Observational studies investigating the connection between hypoglycemia episodes and cognitive impairment will be included. The databases that will be searched are PubMed, Web of Science, the Chinese Biomedical Literature Database (CBM), Cochrane Library, Embase, the China National Knowledge (CNKI), Wan Fang, the Chinese Science and Technology Periodical Database (VIP), and Du Xiu. Literature from the establishment of each database to December 2023 will be included in the search. Two researchers will independently screen the studies that satisfy the requirements for both inclusion and exclusion. A third researcher will be asked to mediate any disputes. The methodological caliber of the studies included will be assessed utilizing the Newcastle-Ottawa Scale (NOS) or the Joanna Briggs Institute (JBI) critical appraisal method. With regard to GRADE, which stands for Grading of Recommendations, Assessment, Development, and Evaluation, the quality of the evidence will be evaluated. ROBIS Tool will be used to evaluate the risk of bias in the development of the systematic review. If the data is accessible, meta-analysis and dose-response curve analysis will be employed by Stata software. However, if the data does not allow for such analysis, a descriptive review will be performed. DISCUSSION AND CONCLUSION: Hypoglycemic episodes may raise the likelihood of cognitive impairment, according to earlier investigations. This study will update the relevant evidence and explore the dose-response connection between hypoglycemic episodes and cognitive impairment. The results of this review will have significant effects on decision-making by individuals with diabetes, healthcare providers, and government policy institutions. TRIAL REGISTRATION: Prospero registration number: CRD42023432352.

In vitro study of genistein inducing apoptosis in MDA-MB-231 breast cancer cells via NF-κB and MAPK signaling pathways / 中国药理学通报

Aim To study the effect of genistein on apoptosis in human breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MTT as-say was used to observe the inhibitory rate on human breast cancer MDA-MB-231 cells treated with genistein. Colony assay was used to determine the cell colony formation rate on human breast cancer MDA-MB-231 cells treated with genistein. Western blot was used to detect the expression of Bcl-2, Bax, caspase-3,NF-κB, ERK, p-ERK, JNK and p-JNK in human breast cancer MDA-MB-231 cells treated with genistein. Results The results of MTT assay showed that genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time- and concentration-de-pendent manner. Colony assay suggested that genistein had an antiproliferative effect on MDA-MB-231 cells. The expression levels of Bcl-2, NF-κB and p-ERK were significantly down-regulated compared with con-trol(P < 0.01). However, the expression of Bax, caspase-3 and p-JNK was significantly up-regulated(P<0.01). Conclusions Genistein could inhibit the growth of human breast cancer MDA-MB-231 cells and induce apoptosis,and the mechanism may be related to the inhibition of NF-κB, ERK/MAPK signaling path-ways and the activation of JNK/MAPK signaling path-way.

Rosmarinic acid derivative RAD-9 induces apoptosis in gastric cancer MGC-803 cells via PI3K/Akt and p38 MAPK signaling pathway / 中国药理学通报

Aim To study the apoptosis-inducing effect of rosmarinic acid derivative RAD-9 on gastric cancer MGC-803 cells and the underlying mechanisms.Methods MTT assay was taken to detect the survival of gastric cancer MGC-803 cells effected by RAD-9.Cell apoptosis was detected by flow cytometry.The apoptotic morphology of MGC-803 cells was observed by Hoechst 33258 staining.The protein expression levels of Bcl-2,Bax,caspase-3,Akt,p-Akt,p38 MAPK and p-p38 MAPK were measured by Western blot.Results The results of MTT assay showed that RAD-9 inhibited the viability of gastric cancer MGC-803 cells in a time and concentration-dependent manner.Flow cytometry showed that RAD-9 significantly promoted apoptotic cell percentage in gastric cancer MGC-803 cells (P ＜ 0.01).Hoechst 33258 staining showed that the nucleus of MGC-803 cells could be observed with typical apoptotic morphological changes after RAD-9 administration.Compared with the control group,the protein expression levels of Bcl-2,Akt,p-Akt were significantly down-regulated (P ＜ 0.01),while those of Bax,caspase-3,p38 MAPK,p-p38 MAPK were significantly up-regulated (P ＜ 0.01).Conclusion RAD-9 can inhibit the growth and further induce apoptosis in gastric cancer MGC-803 cells,which may involve inhibiting PI3K/Akt and activating p38 MAPK signaling pathway.

Citreoviridin Enhances Atherogenesis in Hypercholesterolemic ApoE-Deficient Mice via Upregulating Inflammation and Endothelial Dysfunction.

Vascular endothelial dysfunction and inflammatory response are early events during initiation and progression of atherosclerosis. In vitro studies have described that CIT markedly upregulates expressions of ICAM-1 and VCAM-1 of endothelial cells, which result from NF-κB activation induced by CIT. In order to determine whether it plays a role in atherogenesis in vivo, we conducted the study to investigate the effects of CIT on atherosclerotic plaque development and inflammatory response in apolipoprotein E deficient (apoE-/-) mice. Five-week-old apoE-/- mice were fed high-fat diets and treated with CIT for 15 weeks, followed by assay of atherosclerotic lesions. Nitric oxide (NO), vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) were detected in serum. Levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), VEGF, and ET-1 in plaque areas of artery walls were examined. NF-κB p65 expression and NF-κB activation in aorta also were assessed. CIT treatment significantly augmented atherosclerotic plaques and increased expressions of ICAM-1, VCAM-1, VEGF and ET-1 in aorta. Mechanistic studies showed that activation of NF-κB was significantly elevated by CIT treatment, indicating the effect of CIT on atherosclerosis may be regulated by activation of NF-κB.

Cytotoxic T lymphocyte-associated antigen 4 gene polymorphisms and autoimmune thyroid diseases: an updated systematic review and cumulative meta-analysis.

The association of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) gene and susceptibility to autoimmune thyroid diseases (AITDs) has been studied extensively. However, the results were not the same in different ethnic groups. We updated the meta-analysis of association of CTLA-4 gene polymorphisms with AITDs and summarized the results in specific ethnicity. The associations of A49G gene polymorphism with GD, A49G gene polymorphism with HT, CT60 gene polymorphism with GD, and CT60 gene polymorphism with HT were summarized based on the literatures published up to October 30, 2014, in English or Chinese languages. The participants involved in the studies of A49G with GD, A49G with HT, CT60 with GD, and CT60HT were 39004 subjects (in 51 studies), 13102 subjects (in 22 studies), 31446 subjects (in 22 studies), and 6948 subjects (in 8 studies), respectively. The pooled ORs of CTLA-4 gene polymorphisms with AITDs were larger than 1.00, and the 95% CIs of ORs were statistically significant among whole population analyses. However, the subgroup analysis demonstrated that pooled ORs of A49G polymorphisms with GD among Africans or Americans are less than 1.00. The accumulated evidence suggests that the G allele mutant of A49G and CT60 increased the risks of HT and GD.

Incidences of aortic and mitral valve strands in patients with migraine with aura / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the potential association between valvular strands and migraine with aura.</p><p><b>METHODS</b>During a 1-year period,transesophageal echocardiography was performed in 51 consecutive patients with migraine with aura and 75 control subjects who underwent transesophageal echocardiography for other purposes and had no history of migraine. The presence of aortic and mitral valve strands was evaluated.</p><p><b>RESULTS</b>The incidence of valvular strands was 21.5% (11/51) in migraine patients and 28.0% (21/75) in control subjects (Χ²=0.663, P=0.416). The incidence of patent foramen ovale was significantly higher in patients with migraine with aura than in control subjects (50.9% vs.29.3%) (Χ²=6.302, P=0.012). The incidence of aortic valve strands was significantly higher than that of mitral valve strands in migraine patients (Χ²=4.320,P=0.038).</p><p><b>CONCLUSION</b>Valvular strands are not associated with migraine with aura and show little clinical significance.</p>

Comparison of transthoracic contrast echocardiography and transesophageal contrast echocardiography for detecting right to left shunt in patients with petent foramen ovale / 中华医学超声杂志（电子版）

Objective To compare the effect of transthoracic contrast echocardiography (cTTE) with transesophageal contrast echocardiography (cTEE) for detecting right to left shunt (RLS) in patients with patent foramen ovale (PFO). Methods The prospective study was conducted in 29 consecutive patients with PFO who suffered from cryptogenic stroke and/or migraine. Contrast echocardiography was performed in all 29 patients. The cTTE was performed using transducer with second harmonic imaging modality (transmitting frequency 1.7 MHz, receiving frequency 3.4 MHz). The cTEE was performed using transducer with frequency 7 MHz. Ten milliliter saline solution of contrast were rapidly administrated through an antecubital vein. According to whether microbubble (MB) appearing in left atrium after complete opaciifcation of right atrium within the ifrst 3 circles, the results were classiifed by a four-level semi-quantitative categorization:Level 1 (no PFO-RSL), no MB in left atrium; Level 2 (small PFO-RSL) 1-10 MBs; Level 3 (medium PFO-RSL) 10-30 MBs;Level 4 (large PFO-RSL)>30 MBs. Results The total detection rate of PFO-RSL was signiifcant different between cTTE and cTEE (86.2%vs 55.2%,χ2=5.711, P=0.017). In cTTE there were 4 cases at level 1, 1 case at level 2, 5 cases at level 3 and 19 cases at level 4. In cTEE there were 13 cases at leverl 1, 2 cases at level 2, 6 cases at level 3 and 7 cases at level 4. The comparison of semi-quantitative grading derived from cTTE and cTEE was also signiifcant different (Wilcoxon signed ranks test showed Z=-3.789, P=0.000). Conclusions The efifciency in detection of PFO-RLS with cTTE was better than with cTEE. Compared with cTEE, cTTE was easier in practice and brought less discomfort and complications to patients.

[The cytotoxic effect and injury mechanism of deoxynivalenol on articular chondrocytes in human embryo].

OBJECTIVE: This study was to explore the cytotoxic effect and the related injury mechanism of deoxynivalenol (DON) on articular chondrocytes in human embryo. METHODS: Articular cartilage cells were isolated from knees of human embryo and cultured in DMEM/F12 medium. The cells of the 4th generation were divided into five groups and incubated with varying concentrations of DON as the followings: control group and group with DON of 0.1, 0.2, 0.4, 1.0 µg/ml. The effects of DON were observed 72 hours after incubation. Cell apoptosis was assayed by flow cytometry (FCM) with Annexin V-FITC/PI staining; MMP-13 and PGE2 were detected by ELISA kits; NO was measured by Griess assay with spectrophotometer. Inducible nitric oxide synthase (iNOS) and collagen II in cells were detected by FCM. The expression levels of iNOS, mRNA and collagen II mRNA were measured with RT-PCR. RESULTS: The rates of cell apoptosis in DON groups were 6.78% - 19.05%, which were significantly higher than that in control (1.20%, F = 174.761, P < 0.05). The levels of NO in DON groups were 20.8 - 40.7 µmol/L, which were significantly higher than that in control (10.2 µmol/L, F = 91.966, P < 0.05). The levels of MMP-13 in DON groups were 0.25 - 0.56 µmol/L, which were significantly higher than that in control (0 µmol/L, F = 78.420, P < 0.05). The levels of PGE2 in DON groups were 3.2-20.6 µmol/L, which were significantly higher than that in control (11.6 µmol/L, F = 276.453, P < 0.05). The proportions of cells with positive iNOS in DON groups were 14.8% - 56.8% which were significantly higher than that in controls (7.1%, F = 214.614, P < 0.05). The proportions of cells with positive collagen II in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 56.7% and 52.7%, which were significantly lower than that in control (62.2%, F = 5.134, P < 0.05). The relative absorbance values of iNOS mRNA in DON groups were 1.07 - 1.33, which were significantly higher than that in control (0.62, F = 8.358, P < 0.05). The levels of collagen II mRNA in groups with DON of 0.4 µg/ml and 1.0 µg/ml were 0.83 and 0.82, which were significantly lower than that in control (1.14, F = 7.887, P < 0.05). CONCLUSION: DON could promote anabolism of NO in articular cartilage cells by which up-regulated the expression of PGE2 and MMP-13, which both promoted resolution of articular cartilage matrix such as collagen II. DON induced apoptosis in articular cartilage cells.