Association between ambient particulate matter exposure and mitochondrial DNA copy number: A systematic review and meta-analysis.

BACKGROUND: Ambient particulate matter (PM) has been recognized as inducing oxidative stress, which could contribute to mitochondrial damage and dysfunction. However, studies investigating the association between ambient PM and mitochondria, particularly mitochondrial DNA copy number (mtDNA-CN), have yielded inconsistent results. METHODS: We conducted comprehensive literature searches to identify observational studies published before July 17, 2023, examining the association between ambient PM exposure and mtDNA-CN. Meta-analysis using random effects model was employed to calculate the pooled effect estimates for general individual exposures, as well as for prenatal exposure with specific trimester. Additionally, the quality and level of evidence for each exposure-outcome pair was evaluated. RESULTS: A total of 10 studies were included in the systematic review and meta-analysis. The results indicated that general individual exposure to PM2.5 (ß = -0.084, 95 % CI: -0.521, 0.353; I2 = 93 %) and PM10 (ß = 0.035, 95 % CI: -0.129, 0.199; I2 = 95 %) did not significantly affect mtDNA-CN. Prenatal exposure to PM2.5 (ß = 0.023, 95 % CI: -0.087, 0.133; I2 = 0 %) and PM10 (ß = 0.006, 95 % CI: -0.135; 0.147; I2 = 51 %) were also not significantly associated with mtDNA-CN in offspring. The level of evidence for each tested exposure-outcome pair was assessed as "inadequate." CONCLUSIONS: The findings of this systematic review and meta-analysis indicate that there is an "inadequate" strength of evidence for the association between general individual or prenatal exposure to ambient PM and mtDNA-CN. Future research necessitates studies with more rigorous design, enhanced control of confounding factors, and improved measures of exposure to substantiate our findings.

Short-term effect of meteorological factors and extreme weather events on daily outpatient visits for dry eye disease between 2013 and 2020: a time-series study in Urumqi, China.

Dry eye disease (DED) is a common disorder of tear secretion on the ocular surface caused by multiple factors with dry eyes as the main symptom, but until now studies focusing on relationship between local meteorological factors and ocular surface diseases in Urumqi are very limited. Besides, the effects of long-term and extreme meteorological factors on DED and the lag effect have not been fully evaluated. Electronic case information of 9970 DED outpatients from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) between January 1, 2013, and December 31, 2020, was screened and analyzed. We used a time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) to fit the effects of exposure to different meteorological factors and extreme weather on DED outpatient visits. Subgroup analyses were further performed for gender, age, and season. The results showed that exposure to extremely low mean temperature (P1:RR = 1.18), atmospheric pressure (P1:RR = 1.11), and extremely high relative humidity (P99:RR = 1.35) were the risk factors, while extremely high atmospheric pressure (P90:RR = 0.883) and extremely low humidity (P10:RR = 0.856) appeared to have a positive effect on reduced risk of DED. Relative humidity exhibited a 1-day lag effect (RR = 1.06). Increased mean temperature positively affected female DED patients (RR = 0.761) with similar effects in the cold season (RR = 0.926). However, elevated relative humidity had a negative effect on female patients (RR = 1.14). We conducted the first large sample size time-series analysis study in this major city at the farthest distance from the ocean in the world and in northwest China, confirming the association of DED outpatient visits with the remaining three meteorological factors except wind speed in Urumqi, and a larger sample size multi-center epidemiological study with a longer duration is still needed.

Association of retinopathy with risk of all-cause and specific-cause mortality in the National Health and Nutrition Examination Survey, 2005 to 2008.

Objective: This study aimed to elucidate the relationship between retinopathy status or severity and the all-cause and specific-cause mortality risk based on the updated National Health and Nutrition Examination Survey (NHANES) database and 2019 Public Access Link mortality file. Methods: In this prospective cohort study, a total of 6,797 participants aged over 40 years based on NHANES 2005-2008 were analyzed. The severity of retinopathy was classified into 4 grades-no retinopathy, mild non-proliferative retinopathy (NPR), moderate to severe NPR, and proliferative retinopathy (PR). Multiple covariate-adjusted Cox proportional hazards regression models and Fine and Gray competing risk regression models were used to assess the all-cause and cause-specific mortality risks, respectively. The propensity score matching (PSM) approach was also applied additionally to adequately balance between-group covariates to validate our findings. Results: A final total of 4,808 participants representing 18,282,772 United States (US) non-hospitalized participants were included for analysis, 50.27% were male (n = 2,417), 55.32% were non-hispanic white (n = 2,660), and mean [SE] age, 56.10 [0.40] years. After a median follow-up of 12.24 years (interquartile range, 11.16-13.49 years), 1,164 participants died of all-cause mortality, of which 941 (80.84%) died without retinopathy and 223 (19.16%) died with retinopathy at baseline. The presence of retinopathy was associated with increased all-cause mortality, cardiovascular disease (CVD), and diabetes mellitus (DM)-specific mortality, and the results remain consistent after PSM. Severity analysis showed that only mild NPR was associated with an increased all-cause mortality risk (hazard ratio (HR) = 2.01; 95% confidence interval (CI), 1.00-4.03), while increased CVD and DM-specific mortality risk were associated with all grades of retinopathy and were exponentially greater with increasing retinopathy severity, and the trend test was also significant (P for trend 0.004 and 0.04, respectively). Discussion: Our findings suggest that the diagnosis of retinopathy is an independent risk factor for all-cause mortality in people over 40 years old. Retinopathy grading is significantly associated with the survival risk of patients with CVD or DM, it can be a valuable predictor in the stratified management and risk warning of CVD or DM patients, as well as in the monitoring of systemic vasculopathy status.

Short-term exposure to air pollution and outpatient visits for conjunctivitis: a time-series analysis in Urumqi, China.

Conjunctivitis is an inflammatory disease of the conjunctival tissue caused by a variety of causes; despite the conjunctiva being directly exposed to the external atmospheric environment, the important role of air pollution is not fully evaluated, especially in areas with poor air quality undergoing rapid economic and industrial development. Information on 59,731 outpatient conjunctivitis visits from 1 January 2013 to 31 December 2020 was obtained from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China), and data on six air pollutants including particulate matter with a median aerometric diameter of less than 10 and 2.5 mm (PM10 and PM2.5, respectively), carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), and ozone (O3) from eleven standard urban background fixed air quality monitors were also recorded. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effect of exposure to air pollutants on the risk of conjunctivitis outpatient visits. Further subgroup analyses were conducted for gender, age, and season, as well as the type of conjunctivitis. Single and multi-pollutant models showed that exposure to PM2.5, PM10, NO2, CO, and O3 was associated with increased risk of outpatient conjunctivitis visits on the lag 0 day and various other lag days. Variations in the effect estimates on direction and magnitude were found in different subgroup analyses. We conducted the first time-series analysis with the longest duration as well as the largest sample size in Northwest China, which provides evidence that outpatient conjunctivitis visits is significantly associated with air pollution in Urumqi, China. Meanwhile, our results demonstrate the effectiveness of SO2 reduction in reducing the risk of outpatient conjunctivitis visits in the Urumqi region and reaffirm the need to implement special air pollution control measures.

Long-term effects of meteorological factors and extreme weather on daily outpatient visits for conjunctivitis from 2013 to 2020: a time-series study in Urumqi, China.

Conjunctivitis is a common multifactorial inflammatory ocular surface disease characterized by symptoms such as congestion, edema, and increased secretion of conjunctival tissue, and the potential effects of meteorological factors as well as extreme meteorological factors on conjunctivitis and their lagging effects have not been fully evaluated. We obtained the electronic case information of 59,731 outpatients with conjunctivitis from the Ophthalmology Department of the First Affiliated Hospital of Xinjiang Medical University (Urumqi, Xinjiang, China) for the period from January 1, 2013, to December 31, 2020. Meteorological data for daily mean temperature (°C), daily relative humidity (%), daily average wind speed (m/s), and atmospheric pressure (hPa) were obtained from the China Meteorological Data Sharing Service. The air pollutant data were obtained from 11 standard urban background fixed air quality monitors. A time-series analysis design and a quasi-Poisson generalized linear regression model combined with a distributed lagged nonlinear model (DLNM) were used to fit the effects of exposure to different meteorological factors and extreme weather on conjunctivitis outpatient visits. Subgroup analyses were performed on gender, age and season, and type of conjunctivitis. Univariate and multifactorial model results indicated that each 10-unit increase in mean temperature and relative humidity was associated with an increased risk of conjunctivitis outpatient visits, while each 10-unit increase in atmospheric pressure was associated with a decreased risk. The results of the extreme weather analysis suggested that extremely low levels of atmospheric pressure and relative humidity as well as extreme levels of temperature were associated with an increased risk of outpatient conjunctivitis visits, and extreme wind speeds were associated with a decreased risk. The results of the subgroup analysis suggested gender, age, and seasonal differences. We conducted the first large sample size time-series analysis in the large city furthest from the ocean in the world and confirmed for the first time that elevated mean temperature and extreme low levels of relative humidity in Urumqi were risk factors for local conjunctivitis outpatient visits, while elevated atmospheric pressure and extreme low levels of wind speed were protective factors, and there were lagged effects of temperature and atmospheric pressure. Multicenter studies with larger sample sizes are needed.

Nanoscale coordination polymer Fe-DMY downregulating Poldip2-Nox4-H2O2 pathway and alleviating diabetic retinopathy.

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes and the leading cause of blindness and severe visual impairment in adults. The high levels of glucose trigger multiple intracellular oxidative stress pathways, such as POLDIP2, resulting in excessive reactive oxygen species (ROS) production and increased expression of vascular cell adhesion molecule-1 (VCAM-1), hypoxia-inducible factor 1α (HIF-1α), and vascular endothelial growth factor (VEGF), causing microvascular dysfunction. Dihydromyricetin (DMY) is a natural flavonoid small molecule antioxidant. However, it exhibits poor solubility in physiological environments, has a short half-life in vivo, and has low oral bioavailability. In this study, we present, for the first time, the synthesis of ultra-small Fe-DMY nano-coordinated polymer particles (Fe-DMY NCPs), formed by combining DMY with low-toxicity iron ions. In vitro and in vivo experiments confirm that Fe-DMY NCPs alleviate oxidative stress-induced damage to vascular endothelial cells by high glucose, scavenge excess ROS, and improve pathological features of DR, such as retinal vascular leakage and neovascularization. Mechanistic validation indicates that Fe-DMY NCPs can inhibit the activation of the Poldip2-Nox4-H2O2 signaling pathway and downregulate vital vascular function indicators such as VCAM-1, HIF-1α, and VEGF. These findings suggest that Fe-DMY NCPs could serve as a safe and effective antioxidant and microangio-protective agent, with the potential as a novel multimeric drug for DR therapy.

Association between parenting style and sleep problems among school aged children with autism spectrum disorder / 中国学校卫生

Objective@#To investigate the association between parenting style and sleep problems among school aged children with autism spectrum disorder (ASD).@*Methods@#A total of 98 children with ASD aged 6-10 years old and 98 age and gender matched typically developing (TD) children from mainstream schools were recruited. Parenting style and sleep problems were measured via Parent Behavior Inventory (PBI) and Children s Sleep Habits Questionnaire(CSHQ), respectively. The symptom severity and intelligence level were also evaluated. Generalized linear model was used to analyze the relationship between parenting style and sleep problems.@*Results@#There was no statistically significant difference in the parenting style of the two groups of children( P > 0.05 ); weekend sleep time of children with ASD was significantly shorter than that of the TD group [(9.1±0.7)(9.5±0.8)h, P < 0.01 ], and the score of sleep onset delay was significantly higher than that of the TD group[(1.8±0.7)(1.5±0.7), P <0.01]. However, there was no statistically significant difference in the incidence of total sleep problems and various problems between the two groups of children( P >0.05). The parental support/engagement of children with ASD was negatively associated with the total score of sleep problems( β=-2.68, 95%CI =-4.88--0.47), bedtime resistance ( β=-1.65, 95%CI =-2.54--0.77) and sleep anxiety( β=-1.01, 95%CI =-1.70--0.32). The parental hostility/coercion was positively correlated with score of daytime sleepiness( β=1.41, 95%CI =0.53-2.29)( P <0.05).@*Conclusion@#Parenting style of support/engagement is associated with lower sleep problems in children with ASD, while hostile/coercion is associated with higher sleep problems. It should be improve parental style to reduce the sleep problems in children with ASD.

Efficacy and safety of hypoglycemic drugs in improving cognitive function in patients with Alzheimer's disease and mild cognitive impairment: A systematic review and network meta-analysis.

Objective: The purpose of this study was to compare the effects of oral hypoglycaemic drugs (HDs) on cognitive function and biomarkers of mild cognitive impairment (MCI) and Alzheimer's disease (AD) through a network meta-analysis of randomized controlled trials (RCTs). Methods: We conducted systematic searches for English- and Chinese-language articles in the PubMed, Medline, Embase, Cochrane Library and Google Scholar databases, with no date restrictions. We performed a network meta-analysis, which we report here according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The 16 studies included a total of 3,081 patients. We selected the Mini-Mental State Examination (MMSE), the Alzheimer's Disease Assessment Scale-Cognitive section (ADAS-Cog), the Alzheimer's Disease Cooperative Study Activities of Daily Living section (ADCS-ADL) and amyloid beta (Aß) 42 as the outcome measures for analysis and comparison. Result: We selected seven treatments and assessed the clinical trials in which they were tested against a placebo control. Of these treatments, intranasal insulin 20 IU (ITSN20), glucagon-like peptide-1 (GLP-1), and dipeptidyl peptidase 4 inhibitor (DPP-4) were associated with significantly improved MMSE scores (7 RCTs, 333 patients, 30≥MMSE score≥20: mild) compared with placebo [standardized mean difference (SMD) 1.11, 95% confidence interval (CI) (0.87, 1.35); SMD 0.75, 95% CI (0.04, 1.41); and SMD 4.08, 95% CI (3.39, 4.77), respectively]. Rosiglitazone 4 mg (RLZ4), rosiglitazone 10 mg (RLZ10), intranasal insulin 40 IU (ITSN40), and ITSN20 significantly decreased ADAS-Cog scores (11 RCTs, 4044 patients, 10 ≤ ADAS-Cog scores ≤ 30: mild and moderate) compared with placebo [SMD -1.40, 95% CI (-2.57, -0.23), SMD -3.02, 95% CI (-4.17, -1.86), SMD -0.92, 95% CI (-1.77, -0.08), SMD -1.88, 95% CI (-3.09, -0.66)]. Additionally, ITSN20 and ITSN40 significantly improved ADCS-ADL scores (2 RCTs, 208 patients, ADCS-ADL scale score ≤ 10: mild) compared with placebo [SMD 0.02, 95% CI (0.01, 0.03), and SMD 0.04, 95% CI (0.03, 0.05), respectively]. In the 16 included studies, the degree of AD was classified as mild or moderate. For mild cognitive impairment, DPP-4 performed best, but for mild to moderate impairment, ITSN40 had excellent performance. Conclusion: Various HDs can improve the cognitive function of MCI and AD patients. Different drug regimens brought different degrees of improvement, which may be related to their dosage, duration, and mechanism of action. Systematic review registration: www.crd.york.ac.uk/prospero.

The role of tonifying kidney decoction and acupuncture in the treatment of Alzheimer's disease: A network meta-analysis.

IMPORTANCE: As one of the chronic neurological degenerative diseases with the highest incidence of amnesia and dementia, Alzheimer's disease (AD) carried out the clinical treatment based on the 2 traditional Chinese medicine (TCM) of Chinese herbal compound and acupuncture (AP). With the vigorous development of TCM, doctors are facing the problem of choosing TCM or western medicine in clinical work. Hence there is an urge to make pairwise comparisons among these interventions to provide evidence for clinical practice. OBJECTIVE: The used efficacy of the 2 TCM methods and combined with donepeziline were compared to compile the best treatment through network meta-analysis. METHODS: Patients diagnosed with AD were included in the randomized clinical trial, who were treated with tonifying kidney decoction (TKD) or AP combined with donepezil hydrochloride (DH) as an intervention measure, while the control group was treated with DH. The total effective rate was the primary outcome, and mini-mental state examination (MMSE) score and activities of daily living (ADCS-ADL) scores were the secondary indicators. RESULTS: Eventually 30 studies reporting 2236 patients underwent TKD or AP combined with DH were enrolled. In terms of total efficiency, compared with TKD and DH, TKD + DH was significantly preferable. In addition, TKD were classified into 2 categories, namely tonifying kidney with reducing phlegm formulas (TKRP) and tonifying kidney with filling lean marrow (TKFLM). Regarding to MMSE score of TKD, of the 3 interventions, only TKRP + DH (standard mean difference [SMD] = 4.84, 95% confidence interval [CI]: 0.86-8.82) and TKFLM + DH (SMD = 3.93, 95% CI: 1.06-6.80) had significant efficacy over TKFLM (SMD = 4.25, 95%CI: -2.58 to 11.08). Although no difference between TKRP and other groups, its effectiveness was higher than TKFLM + DH and TKFLM (surface under the cumulative ranking curve (SUCRA) = 61.5%). For the ADL score, compared with TKFLM + DH and DH, TKRP + DH had more effective (SUCRA = 70.2%). Regarding to the total effective rates, AP + DH was more statistically better than AP, and AP was statistically better than DH. CONCLUSION: TKD or AP in combination with DH are significantly superior in treating AD.

The safety and efficacy of melatonin in the treatment of COVID-19: A systematic review and meta-analysis.

BACKGROUND: As an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the common signs of coronavirus disease 2019 (COVID-19) are respiratory symptoms, fever, cough, shortness of breath, and dyspnea, with multiple organ injuries in severe cases. Therefore, finding drugs to prevent and treat COVID-19 is urgently needed and expected by the public. Several studies suggested beneficial effects of melatonin for the relevant prevention and treatment. To explore the effect and safety of melatonin in the treatment and provide theoretical support and reference for seeking the most suitable drug for COVID-19, the meta-analysis was carried out accordingly. METHODS: It included randomized clinical trials of patients with COVID-19 treated with melatonin. Total effective rate was the primary outcome, while C-reactive protein (CRP), arterial oxygen saturation (SaO2), white blood cell count (WBC) were the secondary measures. Random-effect and fixed-effect models were used to evaluate the effect size of some indicators in this meta-analysis. RESULTS: Six eligible studies with 338 participants were included. One hundred seventy subjects were treated with melatonin adjuvant therapy and 168 subjects were assigned to the control group, with total excellent effective rate in subjects treated with melatonin [odds ratio = 3.05, 95 % confidence interval (CI) = 1.47, 6.31, P = .003]. Homogeneity was analyzed by fixed effect model (I2 = 0%). There was no significant difference in CRP between the melatonin group and the control group (weighted mean difference [WMD] = -0.36, 95% CI = -3.65, 2.92, P = .83). Significant difference was not existed in SaO2 between the melatonin treatment group and the control group (WMD = 1, 95% CI = -1.21, 3.22, P = .37). In terms of WBC, there was no significant difference between the 2 groups (WMD = -1.07, 95% CI = -2.44, 0.30, P = .13). CONCLUSIONS: The meta-analysis showed that melatonin had the beneficial effects for COVID-19 prevention and treatment as an adjunctive agent in combination with basic treatment for the treatment.

Berberine Ameliorates Lipopolysaccharide-Induced Cognitive Impairment Through SIRT1/NRF2/NF-κB Signaling Pathway in C57BL/6J Mice.

The inflammatory response is the stress reactions to infection or injury so as to help the body return to normal as soon as possible. In central nervous system, the overactivated immune system causes irreversible damage to neurons and synapses, which results in cognitive impairment. Berberine, an isoquinoline alkaloid extracted from Coptidis Rhizoma, plays a powerful role in anti-inflammation. It has been reported that berberine significantly improved the decline of cognitive ability. Therefore, we carried out this work to find out the specific mechanism. We tested behaviorally that berberine administration did improve lipopolysaccharide (LPS)-induced cognitive impairment in C57BL/6J mice. We found that berberine reduced neuronal damage in the hippocampus by Nissl staining, and verified by western blot and immunofluorescence that berberine improved LPS-induced cognitive impairment through the SIRT1/nuclear factor E2-related factor 2 (NRF2)/nuclear factor-kappaB (NF-κB) signaling pathway. The results showed that berberine plays an anti-inflammatory and antioxidant role by targeting SIRT1/NRF2/NF-κB signaling pathway so as to reduce the cognitive impairment and neuronal damage caused by LPS in C57BL/6J mice. Berberine preprotection increased the expression of heme oxygenase-1 (HO-1) after activating NRF2 and inhibited the activation of NF-κB and the release of inducible NO synthase, which may be related to berberine activating SIRT1. However, the effect of reducing inflammatory response was inhibited after using SIRT1 inhibitor EX527 in vitro. This research explains the significance of anti-inflammatory in the treatment of cognitive impairment from different angles.

Effect of CX3CL1/CX3CR1 gene polymorphisms on the clinical efficacy of carboplatin therapy in Han patients with ovarian cancer.

Gene polymorphisms have a close relationship with the clinical effects of carboplatin for ovarian cancer. Here, we investigated the relationship between CX3CL1 and CX3CR1 genotypes and the clinical efficacy of carboplatin in ovarian cancer, thereby clarifying the unidentified genetic factors that influence the efficacy of carboplatin in ovarian cancer. Based on the above purposes, we used Sequenom Mass ARRAY technology to detect CX3CL1 and CX3CR1 gene polymorphisms in 127 patients with carboplatin-treated ovarian cancer. We performed various statistical analyses to evaluate the effects of CX3CL1 and CX3CR1 genetic variants, demographic data, and clinical characteristics on the effect of carboplatin therapy. The results show that the CX3CL1 genotypes rs223815 (G>C) and rs682082 (G>A) will significantly affect the clinical efficacy of carboplatin for ovarian cancer (p < 0.05), while the other six genotypes and all CX3CR1 genotypes have no significant effect (p > 0.05). In addition, only one population factor, age, had a significant effect on the clinical efficacy of carboplatin-treated ovarian cancer (p < 0.05). Based on the above research results, we concluded that the clinical efficacy of carboplatin in ovarian cancer patients was significantly correlated with age and CX3CL1 polymorphism factors; however, more in-depth effects and mechanisms need to be explored by large-scale, multicenter studies.

Influence of grandparenting involvement on children s oral health / 中国学校卫生

Abstract@#Oral health problems is one of major public health problems that threatens children s overall health. Children s oral health is closely related to family parenting styles. Currently, grandparenting is becoming increasingly common in China, and its impact on children s oral health should not be underestimated. This article reviews the impacts of the oral health knowledge level, behavior habits, gender, socioeconomic status, and other factors related to grandparenting on children s oral health, in order to reduce the negative impact of grandparenting involvement on children s oral health, and to provide theoretical basis and guidance.

Correction: Bushen-Yizhi formula ameliorates cognitive dysfunction through SIRT1/ER stress pathway in SAMP8 mice.

[This corrects the article DOI: 10.18632/oncotarget.17638.].

Kai Xin San ameliorates scopolamine-induced cognitive dysfunction.

Kai Xin San (KXS, containing ginseng, hoelen, polygala, and acorus), a traditional Chinese herbal compound, has been found to regulate cognitive dysfunction; however, its mechanism of action is still unclear. In this study, 72 specific-pathogen-free male Kunming mice aged 8 weeks were randomly divided into a vehicle control group, scopolamine group, low-dose KXS group, moderate-dose KXS group, high-dose KXS group, and positive control group. Except for the vehicle control group and scopolamine groups (which received physiological saline), the doses of KXS (0.7, 1.4 and 2.8 g/kg per day) and donepezil (3 mg/kg per day) were gastrointestinally administered once daily for 2 weeks. On day 8 after intragastric treatment, the behavioral tests were carried out. Scopolamine group and intervention groups received scopolamine 3 mg/kg per day through intraperitoneal injection. The effects of KXS on spatial learning and memory, pathological changes of brain tissue, expression of apoptosis factors, oxidative stress injury factors, synapse-associated protein, and cholinergic neurotransmitter were measured. The results confirmed the following. (1) KXS shortened the escape latency and increased residence time in the target quadrant and the number of platform crossings in the Morris water maze. (2) KXS increased the percentage of alternations between the labyrinth arms in the mice of KXS groups in the Y-maze. (3) Nissl and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining revealed that KXS promoted the production of Nissl bodies and inhibited the formation of apoptotic bodies. (4) Western blot assay showed that KXS up-regulated the expression of anti-apoptotic protein Bcl-2 and inhibited the expression of pro-apoptotic protein Bax. KXS up-regulated the expression of postsynaptic density 95, synaptophysin, and brain-derived neurotrophic factor in the cerebral cortex and hippocampus. (5) KXS increased the level and activity of choline acetyltransferase, acetylcholine, superoxide dismutase, and glutathione peroxidase, and reduced the level and activity of acetyl cholinesterase, reactive oxygen species, and malondialdehyde through acting on the cholinergic system and reducing oxidative stress damage. These results indicate that KXS plays a neuroprotective role and improves cognitive function through reducing apoptosis and oxidative stress, and regulating synapse-associated protein and cholinergic neurotransmitters.

Role of Xingnaojing combined with naloxone in treating intracerebral haemorrhage: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Xingnaojing injection (XNJ) sharpen the mind and induce consciousness and are widely used in acute phases of intracerebral hemorrhage (ICH). Naloxone hydrochloride injection (NX) performs equally well and replace the effects of morphine-like substances to promote conscious awareness. The applications of XNJ combined with NX for ICH show some advantages compared with NX applied individually. The aim of this systematic review is to evaluate the effectiveness and safety of XNJ combined with NX for ICH. METHODS: Comprehensive searches were conducted in 8 medical databases (PubMed, Cochrane Library, Web of Science, Embase, CNKI, VIP, CBM and Wanfang database) from inceptions to October 2017 for randomized controlled trials (RCTs) that compared the applications of XNJ and NX with NX applied individually in ICH. Literature screening, assessing risk of bias and data extraction were conducted by 2 reviewers independently. According to the Cochrane Collaboration's RevMan5.3 software to perform the data analysis. RESULTS: 32 RCTs (3068 cases) were selected and the quality of studies were low. All trials compared XNJ and NX with NX applied individually. The overall meta-analysis results showed that XNJ combined with NX have significant effect on clinical efficacy (OR 3.78, 95% CI: 3.03-4.73; P < .00001), GCS score (MD 3.86, 95% CI: 3.46-4.25; P < .00001), coma duration (MD -5.59, 95% CI: -6.96 to -4.22; P < .00001), NIHSS score (MD -6.24, 95% CI: -8.05 to -4.42; P < .00001), Barthel Index score (MD 14.12, 95% CI: 6.7-21.54; P < .0002), cerebral hematoma volume (MD -6.05, 95% CI: -6.85 to -5.24; P < .00001) than NX applied individually. Adverse events reported in 4 studies and included mild discomfort symptoms. CONCLUSION: The effectiveness and safety of XNJ combined with NX for ICH cannot be determined due to the low quality of literature, publication bias and heterogeneity. More rigorous RCTs are necessary to verify the role of XNJ combined with NX in the treatment of ICH.

Jiao-Tai-Wan Improves Cognitive Dysfunctions through Cholinergic Pathway in Scopolamine-Treated Mice.

Cognitive dysfunction is characterized as the gradual loss of learning ability and cognitive function, as well as memory impairment. Jiao-tai-wan (JTW), a Chinese medicine prescription including Coptis chinensis and cinnamon, is mainly used for the treatment of insomnia, while the effect of JTW in improving cognitive function has not been reported. In this study, we employed a scopolamine- (SCOP-) treated learning and memory deficit model to explore whether JTW could alleviate cognitive dysfunction. In behavioral experiments, Morris water maze, Y-maze, fearing condition test, and novel object discrimination test were conducted. Results showed that oral administration of JTW (2.1 g/kg, 4.2 g/kg, and 8.4 g/kg) can effectively promote the ability of spatial recognition, learning and memory, and the memory ability of fresh things of SCOP-treated mice. In addition, the activity of acetylcholinesterase (AChE) was effectively decreased; the activity of choline acetyltransferase (ChAT) and concentration of acetylcholine (Ach) were improved after JTW treatment in both hippocampus and cortex of SCOP-treated mice. JTW effectively ameliorated oxidative stress because of decreased the levels of malondialdehyde (MDA) and reactive oxygen species (ROS) and increased the activities of superoxide dismutase (SOD) and catalase (CAT) in hippocampus and cortex. Furthermore, JTW promotes the expressions of neurotrophic factors including postsynaptic density protein 95 (PSD95) and synaptophysin (SYN) and brain-derived neurotrophic factor (BDNF) in both hippocampus and cortex. Nissl's staining shows that the neuroprotective effect of JTW was very effective. To sum up, JTW might be a promising candidate for the treatment of cognitive dysfunction.

[Expression of MiR-296-5p in Diffuse Large B-Cell Lymphoma and Its Influence on Biological Behavior of Tumor Cells].

OBJECTIVE: To detect the expression of miRNA-296-5p in diffuse large B cell lymphoma (DLBCL) cells and study the proliferation, migration and apoptosis of DLBCL cells after interfering the expression of miRNA-296-5p. METHODS: The expression of miRNA-296-5p in DLBCL cells line DB cells was detected by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR). The possible roles of miRNA-296-5p in the biological and behavioral properties of DLBCL-DB cells were explored by transfection of miRNA-296-5p inhibitor for miRNA-296-5p knockdown, and detected by using CCK-8 method, Transwell method and Annexin V-FITC/PI. RESULTS: miRNA-296-5p was highly expressed in DLBCL-DB cells, and the inhibition of miRNA-296-5p could induce suppression of cell proliferation and migration, but the cell apoptosis was not changed significantly. CONCLUSION: The high expression of miRNA-296-5p may relate with the occurence and development of DLBCL, which may be a new therapeutic target for DLBCL.

[Expression and Clinical Prognostical Significance of RIP2 in Diffuse Large B Cell Lymphoma].

OBJECTIVE: To investigate the expression and prognosis significance of receptor interacting protein 2 (RIP2) in diffuse large B-cell lymphoma (DLBCL). METHODS: The expression of RIP2 in DLBCL GCB and non-GCB type was detected by immunohistochemistry, at same time the expressions of BCL-2 and C-MYC were detected. Then, the role of RIP2 in development of DLBCL was analyzed by related clinical and pathological parameters. RESULTS: The expression of RIP2 was related with middle-high risk group by IPI score, the An Arbor stage III+IV and intranodal lesions, and the differences were statistically significant (P<0.05). Besides, the single factor survival analysis suggested that GCB-type DLBCL showed a higher survival rate than that in non-GCB type(P<0.05). Patients with RIP2+ showed a lower survival rate as compared with patients with PIP2- (P<0.05), among which the patients receiving R-CHOP had a higher survival rate than that of those receiving CHOP (P<0.01). The expression of RIP2 in DLBCL cell lines was higher than that in peripheral mononuclear cells of normal subjects (P<0.01) and expressed differently in DLBCL of GCB and non-GCB type (P<0.01). CONCLUSION: The expression of RIP2 may relate with the poor prognosis and specific subtype of DLBCL.

Berberine Improves Diabetic Encephalopathy Through the SIRT1/ER Stress Pathway in db/db Mice.

The association between diabetes and dementia has been well demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related protein expression (PSD95, SYN, and NGF) and decreased the protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the protein expression of SIRT1 and downregulated ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the SIRT1/ER stress pathway might be a crucial mechanism in the neuroprotective effect of BBR against DE.