Hidden dangers: Does multisensory impairments accompanying visual impairment increase dementia risk.

BACKGROUND: Growing evidence suggests that sensory impairment, particularly in the form of visual impairment, may contribute to the development of dementia. However, it remains unclear whether experiencing concurrent visual impairment in combination with other types of multisensory impairments may further increase this risk. METHODS: The study used data from the UK Biobank cohort study, which recruited 500,000 adults. With meticulous screening procedures in place, individuals with visual impairment, hearing impairment, and oral health issues were identified for further follow-up evaluations. A multivariable regression analysis was conducted to investigate the relationship between multisensory impairments concurrent with visual impairment and cognitive function. Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals to evaluate the association between multisensory impairments concurrent with visual impairment and dementia risk. RESULTS: Subjects experiencing multisensory impairments concurrent with visual impairment demonstrated a negative association with cognitive function. Notably, individuals who have both vision and hearing impairments had a significantly higher risk of developing dementia (HR 1.28, 95% CI [1.01-1.63]). Additionally, individuals who experience vision impairment and oral health issues simultaneously were also at higher risk for dementia (HR 1.61, 95% CI [1.32-1.97]). Furthermore, the risk of dementia among individuals with vision impairment, hearing impairment, and oral health issues further escalated to an even higher level (HR 1.63, 95% CI [1.19-2.24]). CONCLUSIONS: The correlation between the presence of multisensory impairments concurrent with visual impairment and cognitive decline is highly significant. Those with multisensory impairments concurrent with visual impairment are at a significantly increased risk of developing dementia.

The effect of the leisure activities based on chess and cards for improving cognition of older adults: study protocol for a cluster randomized controlled trial.

BACKGROUND: With the increase in age, the probability of cognitive impairment in the older people is increasing. More and more evidence shows that participating in leisure activities, especially chess and cards, is beneficial to the cognition and mental state of the older people. But the evidence for causal inference is limited. There is a need to conduct a fully powered randomized controlled trial (RCT) and long-term follow-up to test the effectiveness of intervention measures in improving cognitive function and mental state. This paper describes the methodology of a cluster RCT designed to determine the effect of chess and cards leisure activities on the cognitive function of the older people over 60 years old. METHODS/DESIGN: A cluster RCT consisting of 8 clusters will be conducted in four regions of Ningxia, China (Helan, Litong, Qingtongxia, and Shapotou). Clusters will be randomly assigned to the advocacy intervention group, which is also delivered with free leisure activities tools (chess and cards), or the control group. A baseline survey will be conducted before the intervention. A mid-term and final survey will be carried out twelve and twenty-four months after the intervention, respectively. The primary outcome is a change in cognitive function, and the secondary outcomes are changes in anxiety, depression, and loneliness. DISCUSSION: The results of this RCT will be helpful to (1) confirm the effectiveness of chess and cards leisure activities in improving the cognitive function of the older people over 60 years old; (2) determine the relationship between the frequency and duration of chess and cards leisure activities and cognitive function; (3) provide evidence of promoting participation in leisure activities through education campaigns and free provision of chess and cards tools; and (4) provide valuable information for successful aging. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2200066817. Registered on 19 December 2022.

Individuals with T-786C and G894T genotypes of eNOS in Chinese Han population have an increased risk of developing rheumatoid arthritis.

Several genetic polymorphisms in endothelial nitric oxide synthase (eNOS) are associated with the pathogenesis of rheumatoid arthritis (RA). This study explored the effect of eNOS gene polymorphism on genetic susceptibility of RA in Chinese Han population. Patients with RA (n=236) and healthy volunteers (n=240) were enrolled in this study. Genotyping of eNOS T-786C and G894T polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism. Genotyping and gene frequency distribution of eNOS T-786C and G894T polymorphisms were evaluated. RA patients showed higher frequencies of mutated TC and CC genotypes of eNOS T-786C polymorphism and mutated GT and TT genotypes of G894T polymorphism than healthy controls. More specifically, the genotype frequencies of eNOS T-786C polymorphism were significantly different between RA patients and controls. The expression of eNOS was enhanced in RA patients compared with controls. Further, eNOS expression was enhanced after C was replaced with T in T-786C polymorphism in the promoter. Overall, the individuals with mutations in T-786C and G894T of eNOS may have an increased risk of RA, and T-786C and G894T polymorphisms of eNOS are associated with genetic susceptibility of RA in Chinese Han population.

[The Activity Characteristics of ABO Blood Group Glycosyltransferases and the Effect of Plasma Preservation on its activity].

OBJECTIVE: Activities of ABO blood group glycosyltransferases in the plasma of blood donors with different blood groups were detected to discover their normal ranges. In addition, the influence of different plasma storage temperatures and time on the enzyme activity was studied, so as to establish a stable ABO blood group glycosyltransferase activity detection technology system for the auxiliary identification of ABO blood groups. METHODS: Detect the activities of glycosyltransferase A (GTA) in plasma of type A, AB and O blood donors, and glycosyltransferase B (GTB) in plasma of type B, AB and O blood donors, respectively, to determine the activity range of GTA and GTB in the plasma of normal blood group under this detection technique. RESULTS: The activities of GTA and GTB in plasma of the same ABO blood groups were relatively consistent, while significant difference was found among different ABO blood groups. The activity of GTA was around 27.9±0.3 in plasma of A blood group and 28.3±0.5 in plasma of AB blood group. The activity of GTB in plasma of B blood group was about 24.4±0.5, and that in plasma of AB blood group was about 25.6±0.5. The activities of GTA and GTB in plasma of O blood group were negative. The storage temperature and time of plasma would affect the activities of GTA and GTB. There were no significant changes of the activities of GTA and GTB when the plasma was stored at 4 ℃ for 7 days and -40℃ for 21 days. However, after 28 days of storage at -40 ℃, the activities of GTA and GTB were both decreased significantly. CONCLUSION: The preservation condition suitable for the detection of ABO glycosyltransferase activity in plasma samples contain short-term storage at 4 ℃ for one week, and cryopreserved at -40 ℃ for no more than three weeks.

Mycoplasma pneumoniae downregulates RECK to promote matrix metalloproteinase-9 secretion by bronchial epithelial cells.

Airway epithelial cells function as both a physical barrier against harmful substances and pathogenic microorganisms and as an important participant in the innate immune system. Matrix metalloproteinase-9 (MMP-9) plays a crucial role in modulating inflammatory responses during respiratory infections. However, the signalling cascade that induces MMP-9 secretion from epithelial cells infected with Mycoplasma pneumoniae remains poorly understood. In this study, we investigated the mechanism of MMP-9 secretion in airway epithelial cells infected with M. pneumoniae. Our data clearly showed that M. pneumoniae induced the secretion of MMP-9 from bronchial epithelial cells and upregulated its enzymatic activity in a time- and dose-dependent manner. Using specific inhibitors and chromatin co-precipitation experiments, we confirmed that the expression of MMP-9 is reliant on the activation of the Toll-like receptor 2 (TLR2) and TLR6-dependent mitogen-activated protein kinase/nuclear factor- κB/activator protein-1 (MAPK/NF-κB/AP-1) pathways. Additionally, epigenetic modifications such as histone acetylation and the nuclear transcription factor Sp1 also regulate MMP-9 expression. M. pneumoniae infection also decreased the expression of the tumour suppressor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) by inducing Sp1 phosphorylation. Overexpression of RECK significantly impaired the M. pneumoniae-triggered increase in MMP-9 enzymatic activity, although the level of MMP-9 protein remained constant. The study demonstrated that M. pneumoniae-triggered MMP-9 expression is modulated by TLR2 and 6, the MAPK/NF-κB/AP-1 signalling cascade, and histone acetylation, and M. pneumoniae downregulated the expression of RECK, thereby increasing MMP-9 activity to modulate the inflammatory response, which could play a role in airway remodelling.

Accurate Detection of Hepatitis B Virus G1896A Mutant by Developed Taqman-ARMS Followed a Strict Control System.

BACKGROUND: Hepatitis B virus (HBV) G1896A mutation was associated with HBeAg seronegativity and hepatitis B related acute-on-chronic liver failure. In this study, we developed Taqman amplification refractory mutation system (Taqman-ARMS) and established a strict control system to detect HBV G1896A mutant. METHODS: HBV viral DNA was isolated from 60 patient serum samples, and full-length HBV genome was cloned. Then, Taqman-ARMS was used to detect HBV G1896A mutant. RESULTS: The assay has the sensitivity of 1E+3 IU/ml G1896A template, and 0.1% weak population virus with G1896A could be found in mixtures. Total of all 60 clinical samples random collected were detected by Taqman-ARMS, the results were consistent with those by DNA sequencing. CONCLUSION: The proposed Taqman-ARMS real-time PCR method for the detection of G1896A mutation of HBV was rapid, simple, sensitive, specific, and applicable in the clinical setting.

Preparation and evaluation of dl-praeruptorin A microemulsion based hydrogel for dermal delivery.

The purpose of the present investigation was to develop and optimize the microemulsion (ME) as a transdermal system for Pd-Ia, a poor water soluble and low bioavailable drug. The pseudo-ternary phase diagrams were constructed for various ME formulations including oleic acid as the oil phase, Cremophor RH40 as the surfactant, ethanol as the cosurfactant, and water. The maximum cumulative amount permeated through rat abdominal skins per unit area in 32 h (Q32), and the maximum flux were evaluated using the Franz diffusion cell in order to optimize the ME formulation. The results indicated that the optimized ME formulation was composed of oleic acid (5%, W/W), Cremophor RH40 (13.33%, W/W), ethanol (26.67%, W/W), and water (55%, W/W); the maximum cumulative amount of Pd-Ia was 354.330 ± 12.006 µg cm(-2), the maximum flux was 11.467 ± 0.500 µg cm(-2)h(-1). ME-gel was administered transdermally to rats. The mean plasma concentration of Pd-Ia following transdermal application of ME-gel could be maintained for 32 h at least and the half-life was evidently prolonged. It shows that the ME-gel could be a promising vehicle for dermal delivery of Pd-Ia.

[Integrated regional network construction for ST-segment elevation myocardial infarction care].

OBJECTIVE: To investigate the feasibility of establishing an integrated regional network for ST-segment elevation myocardial infarction (STEMI) care in China and evaluate the implementation effect of this network. METHODS: Based on real-time electrocardiogram transmission technology, we established an integrated regional network for STEMI care (IRN-STEMI) with Xiamen Heart Center as the core center, 120 Emergency Systems, PCI-capable hospitals and other community health units as core elements of this network. Reperfusion treatment data of Xiamen Heart Center including the number of patients receiving primary percutaneous coronary intervention (PCI), the mean first medical contact to balloon (FMC-to-B) time, the mean door to balloon (D-to-B) time, the mean length of hospital stay, the mean medical cost and in-hospital mortality were compared before (n = 165) and at 1 year after the built-up of IRN-STEMI (n = 343). RESULTS: Compared to pre-IRN-STEMI era, primary PCI ratio (84.5% (290/343) vs. 75.5% (185/245)) were significantly increased post establishment of IRN-STEMI within the network (P = 0.06). STEMI patients admitted in Xiamen Heart Center was significantly increased from 165 to 256, the annual mean FMC-to-B time ((110.3 ± 34.0)min vs. (137.9 ± 58.5) min, P < 0.01) and D-to-B ( (76.5 ± 33.0) min vs. (107.3 ± 38.0) min, P < 0.01) , as well as the mean medical cost were significantly decreased ( (51 398 ± 22 100) RMB vs. (56 970 ± 24 593) RMB, P < 0.05), while the mean length of hospital stay ((9.0 ± 4.3)d vs. (9.7 ± 4.8)d, P > 0.05) and in-hospital mortality (3.1% (8/256) vs. 3.0% (5/165) , P > 0.05) remained unchanged before and after the setting of IRN-STEMI in Xiamen Heart Center. CONCLUSION: Establishment of an integrated regional network system for STEMI patients in China is feasible. With collaboration of qualified heart center, EMS and PCI-capable and non-PCI capable local hospitals, establishment of IRN-STEMI effectively increased the ratio of primary PCI for STEMI patients, it also significantly shortened the FMC-to-B and D-to-B time, decreased mean medical cost, thus, the regional IRN-STEMI network might be an effective working system for improving the medical care for STEMI patients.

[SCD1 over-expression inhibits palmitic acid-induced apoptosis of rat BRL hepatocytes].

OBJECTIVE: To investigate the protective mechanism of stearoyl-CoA desaturase 1 (SCD1) over-expression against the pro-apoptotic affects of palmitic acid on hepatocytes using the rat BRL cell line. METHODS: Concentration effect curves were generated using the trypan blue exclusion test to assess the death rate of BRL cells upon exposure to a dilution series of palmitic acid. The multiplicity of infection (MOI) of a lentiviral expression vector, pGC-FU-GFP, was determined for the BRL cells. Unmanipulated BRL cells were divided into two groups: the non-palmitate groups were composed of ordinary cultured cells (CON) alone, infected with lentivirus empty expression vector (negative control, NC), and infected with lentivirus overexpressing SCD1 (SCD1-LV); the palmitate groups were composed of ordinary cultured cells plus palmitate (CON+) alone, infected with lentivirus empty expression vector plus palmitate (NC+), and infected with lentivirus overexpressing SCD1 plus palmitate (SCD1-LV+). SCD1 mRNA expression was detected by real-time PCR. Propidium iodide (PI) single-staining was used to detect apoptosis and assess the cell cycle. Inter-group differences were analyzed statistically. RESULTS: The death rate of BRL cells increased significantly after 72 h of exposure to 400 mumol/L palmitate (P less than 0.01). The MOI of pGC-FU-GFP in BRL cells was 20. The expression of SCD1 was significantly higher in the SCD1-LV and SCD1-LV+ groups than in the respective controls (vs. CON: F = 289, P less than 0.01; vs. CON+: F = 1522, P less than 0.01). Palmitate exposure led to decreased expression of SCD1 (CON+ vs. CON, F = 22, P less than 0.05 and NC+ vs. NC: F = 34, P less than 0.05). The ratio of S stage cells was similar in all non-palmitate groups (CON, NC and SCD1-LV, P = 0.137). However, there was a significant apoptotic peak and lower ratio of S stage cells in the control palmitate groups (CON+ and NC+) and the activity of cell proliferation was decreased as well. The ratio of apoptotic cells was decreased significantly in the SCD1-LV+ group compared to the CON+ group (P less than 0.01). CONCLUSION: The expression of SCD1 and its desaturation activity increased in BRL cells upon infection with the pGC-FU-SCD1-GFP lentiviral vector, suggesting that SCD1 over-expression can decrease palmitic acid-induced toxicity and apoptosis in hepatocytes.

Pemetrexed plus platinum as the first-line treatment option for advanced non-small cell lung cancer: a meta-analysis of randomized controlled trials.

UNLABELLED: To compare the efficacy and toxicities of pemetrexed plus platinum with other platinum regimens in patients with previously untreated advanced non-small cell lung cancer (NSCLC). METHODS: A meta-analysis was performed using trials identified through PubMed, EMBASE, and Cochrane databases. Two investigators independently assessed the quality of the trials and extracted data. The outcomes included overall survival (OS), progression-free survival (PFS), response rate (RR), and different types of toxicity. Hazard ratios (HRs), odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled using RevMan software. RESULTS: Four trials involving 2,518 patients with previously untreated advanced NSCLC met the inclusion criteria. Pemetrexed plus platinum chemotherapy (PPC) improved survival compared with other platinum-based regimens (PBR) in patients with advanced NSCLC (HR = 0.91, 95% CI: 0.83-1.00, p = 0.04), especially in those with non-squamous histology (HR = 0.87, 95% CI: 0.77-0.98, p = 0.02). No statistically significant improvement in either PFS or RR was found in PPC group as compared with PBR group (HR = 1.03, 95% CI: 0.94-1.13, p = 0.57; OR = 1.15, 95% CI: 0.95-1.39, p = 0.15, respectively). Compared with PBR, PPC led to less grade 3-4 neutropenia and leukopenia but more grade 3-4 nausea. However, hematological toxicity analysis revealed significant heterogeneities. CONCLUSION: Our results suggest that PPC in the first-line setting leads to a significant survival advantage with acceptable toxicities for advanced NSCLC patients, especially those with non-squamous histology, as compared with other PRB. PPC could be considered as the first-line treatment option for advanced NSCLC patients, especially those with non-squamous histology.

Association of APOE polymorphisms and insulin resistance with TCM syndromes in type 2 diabetes patients with macroangiopathy.

To investigate the association between apolipo-protein E (APOE) polymorphisms and insulin resistance and Traditional Chinese Medicine (TCM) syndromes in type 2 diabetes mellitus (T2DM) with macroangiopathy, 60 patients with T2DM macroangiopathy were enrolled and divided into three groups: dryness-heat due to deficiency of yin, Qi-Yin deficiency, and Yin-Yang deficiency, according to the TCM syndromes, with a control group of 20 healthy individuals. APOE genotype analysis was performed with polymerase chain reaction amplification and restriction fragment length polymorphism, and the results showed that the proportion of the ε4/4 and ε3/4 genotypes and frequencies of the ε4 and ε3 alleles were higher in the Qi-Yin deficiency group (P<0.05). Among the T2DM macroangiopathy patients, the E4 group had the largest number of cases, as well as a significantly longer disease course compared to the E2 group (P<0.05). The insulin resistance index (IRI), insulin action index and body mass index (BMI) of patients in the Yin-Yang deficiency group were significantly different from those of patients with dryness-heat due to deficiency of yin and Qi-Yin deficiency. Furthermore, correlation analysis of the BMI and IRI of patients in the Yin-Yang deficiency group revealed a correlation coefficient r=0.696 (P<0.01) and a typical correlation between them. In conclusion, the Qi-Yin deficiency in T2DM patients with macroangiopathy is associated with the APOE E4 and E3 genotypes. Thus, the APOE gene polymorphism can, to some degree, reflect the TCM syndrome types of T2DM patients with macroangiopathy. Insulin resistance plays an important role in the occurrence of T2DM macroangiopathy and is closely associated with the Yin-Yang deficiency according to the TCM differentiating types.

Serum APRIL, a potential tumor marker in pancreatic cancer.

BACKGROUND: A proliferation-inducing ligand (APRIL) is a newly-found member in the tumor necrosis factor (TNF) superfamily. Our previous studies have already confirmed that APRIL is overexpressed in pancreatic cancer tumors, however, it is not expressed or has a weak expression in normal pancreatic gland tissues. Furthermore, there is no report on serum APRIL in patients with pancreatic diseases. Herein, in order to explore the clinical implication of serum APRIL in patients with pancreatic cancer, serum APRIL, together with carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9, was examined. METHODS: Serum APRIL was tested by ELISA in patients with pancreatic cancer. Meanwhile, two other conventional serum tumor markers, CEA and CA19-9, were measured by Elecsys 2010 Chemistry Analyzer. RESULTS: Serum APRIL increased in patients with pancreatic cancer, which proved a positive correlation with CEA and CA19-9. When the diagnosis of benign or malignant condition was examined by one tumor marker, the sensitivity of APRIL alone (70.1%) was greater than that of CEA alone (56.7%), and the specificity of APRIL alone (85.5%) was higher than that of CA19-9 alone (83.6%). When examined by a combination of two markers, the sensitivity of the combination of APRIL and CA19-9 was the highest (88.1%), as it was compared with that of APRIL alone, CEA alone and APRIL+CEA, p<0.05. In addition, serum APRIL also correlated with the tumor stage and postoperative survival in patients with pancreatic cancer. CONCLUSIONS: Our results indicate that serum APRIL, as a potential biomarker, has a positive diagnosis and prognosis value for pancreatic cancer. Moreover, the combination assay of APRIL and CA19-9 is highly sensitive to pancreatic cancer.

[Gene mutation in the areas of PreC/C and BCP of HBV DNA].

OBJECTIVE: To investigate the gene mutation in the areas of pre core/core (Pre C/C) and basic core promotor (BCP) of HBV DNA and its clinical significance. METHODS: The nt 1 735-1 965 segment of HBV DNA was amplified with PCR in 54 cases with chronic hepatitis B and 10 cases with post-hepatitis cirrhosis. Then the PCR product was sequenced. RESULTS: There were 168 site mutations in 48.5% (33/68) cases with hepatitis B. The first ten mutation sites were nt 1 764 (58.8%), 1 762 (48.5%), 1 799 (21.0%), 1 766 (14.7%), 1 896 (13.2%), 1 754 (8.8%), 1 899 (8.8%), 1 768 (7.4%), 1 814 (7.4%) and 1 913 (7.4%). Three rare mutations of nt 1907, 1 922 and 1 923 were also detected. The mutations of nt 1 896, 1 764 and 1 762 were found in 16.7%, 35.2% and 35.2% of chronic hepatitis, and in 30.0%, 60.0% and 60.0% respectively of post-hepatitis cirrhosis cases. There was statistical significance between the two groups (P < 0.01). CONCLUSION: The mutations in the areas of Pre C/C and BCP of HBV DNA might possibly be associated with liver fibrosis. There are many mutation sites in HBV DNA and mutation occurs frequently, therefore gene sequencing is helpful to the design of gene chip and to clinical application.