The casual relationship between autoimmune diseases and multiple myeloma: a Mendelian randomization study.

Observational studies showed possible associations between systemic lupus erythematosus and multiple myeloma. However, whether there is a casual relationship between different types of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus, psoriasis, multiple sclerosis, primary sclerosing cholangitis, primary biliary cirrhosis, and juvenile idiopathic arthritis) and multiple myeloma (MM) is not well known. We performed a two-sample Mendelian randomization (MR) study to estimate the casual relationship. Summary-level data of autoimmune diseases were gained from published genome-wide association studies while data of MM was obtained from UKBiobank. The Inverse-Variance Weighted (IVW) method was used as the primary analysis method to interpret the study results, with MR-Egger and weighted median as complementary methods of analysis. There is causal relationship between primary sclerosing cholangitis [OR = 1.00015, 95% CI 1.000048-1.000254, P = 0.004] and MM. Nevertheless, no similar causal relationship was found between the remaining seven autoimmune diseases and MM. Considering the important role of age at recruitment and body mass index (BMI) in MM, we excluded these relevant instrument variables, and similar results were obtained. The accuracy and robustness of these findings were confirmed by sensitivity tests. Overall, MR analysis suggests that genetic liability to primary sclerosing cholangitis could be causally related to the increasing risk of MM. This finding may serve as a guide for clinical attention to patients with autoimmune diseases and their early screening for MM.

Comparison of the effects of using feedback devices for training or simulated cardiopulmonary arrest.

BACKGROUND: High-quality chest compression is essential for successful cardiac arrest resuscitation. High-quality cardiopulmonary resuscitation (CPR) can effectively improve the survival rate of patients with cardiopulmonary arrest. However, bystanders untrained in cardiopulmonary resuscitation may provide inadequate chest compressions. Previous studies have shown that the use of feedback devices in training alone or in simulated cardiopulmonary arrest alone can improve cardiopulmonary resuscitation. This study aims to determine whether using an audiovisual feedback (AVF) device during CPR training or a simulated cardiopulmonary arrest (CA) scenario would be more effective in improving the quality of chest compressions (CC). METHODS: We use a prospective, randomized, 2 × 2 factorial design trial. A total of 160 participants from Wuhan University and senior clinical medicine undergraduates who had not participated in any CPR training before and had no actual CPR experience are recruited. Each participant is randomized to 1 of 4 permutations, including AVF device vs. no AVF device during CPR training and AVF device vs. no AVF device during simulated CA. Main outcomes and measures are the depth, the percentage of CCs with correct depth (5-6 cm), the rate of CCs, and the percentage of CCs with the correct rate (100-120 cpm). RESULTS: The use of the AVF device during simulated CA resulted in improved CC quality. In CA without AVF device, the average compression depth and the percentage of adequate depth with AVF device are 5.1 cm, 5.0 cm and 55.5%, 56.3%, respectively, which are higher than those without AVF device (4.5 cm, 4.7 cm and 32.8%, 33.6%). (p = 0.011, p = 0.000, both < 0.05).Compared with CA without AVF device, the average compression rate and the percentage of adequate rate with AVF device are 112.3 cpm, 111.2 cpm and 79.4%, 83.1%, respectively. The average compression rate and the percentage of adequate rate without using the AVF device are 112.4 cpm, 110.3 cpm and 71.5%, 68.5%, respectively. (p = 0.567 > 0.05, p = 0.017 < 0.05)Although the average compression rate in group D is slightly lower than that in group C, the percentage of suitable frequency with the feedback device is still higher than that without AVF device. CONCLUSION: Using a feedback device during simulated cardiopulmonary arrest is more effective in improving cardiopulmonary resuscitation than during training.

Combination of On-Line and Off-Line Two-Dimensional Liquid Chromatography-Mass Spectrometry for Comprehensive Characterization of mAb Charge Variants and Precise Instructions for Rapid Process Development.

Charge variants, as an important quality attribute of mAbs, must be comprehensively characterized and monitored during development. However, due to their complex structure, the characterization of charge variants is challenging, labor-intensive, and time-consuming when using traditional approaches. This work combines on-line and off-line 2D-LC-MS to comprehensively characterize mAb charge variants and quickly offer precise instructions for process development. Six charge variant peaks of mAb 1 were identified using the developed platform. Off-line 2D-LC-MS analysis at the peptide level showed that the acidic peak P1 and the basic peaks P4 and P5 were caused by the deamidation of asparagine, the oxidation of methionine, and incomplete C-terminal K loss, respectively. On-line 2D-LC-MS at the intact protein level was used to identify the root causes, and it was found that the acidic peak P2 and the basic peak P6 were due to the glutathionylation of cysteine and succinimidation of aspartic acid, respectively, which were not found in off-line 2D-LC-MS because of the loss occurring during pre-treatment. These results suggest that process development could focus on cell culture for adjustment of glutathionylation. In this paper, we propose the concept of precision process development based on on-line 2D-LC-MS, which could quickly offer useful data with only 0.6 mg mAb within 6 h for precise instructions for process development. Overall, the combination of on-line and off-line 2D-LC-MS can characterize mAb charge variants more comprehensively, precisely, and quickly than other approaches. This is a very effective platform with routine operations that provides precise instructions for process development within hours, and will help to accelerate the development of innovative therapeutics.

Probiotics Alleviate Chemotherapy-Associated Intestinal Mucosal Injury via the TLR4-NFκB Signaling Pathway.

Introduction: Temozolomide (TMZ) induces intestinal mucosa injury that cannot be fully counteracted by supportive treatment. Probiotics regulate gut microbial composition and the host immune system and may alleviate this side effect. We aimed to investigate the potential and mechanism of Lactobacillus rhamnosus GG (LGG) in relieving intestinal mucosal injury induced by TMZ. Methods: Glioblastoma mice were divided into four groups: CON (control), LGG (109 CFU/mL, treated for 7 days), TMZ (50 mg/kg·d, treated for 5 days), LGG+TMZ (LGG for 7 days and TMZ subsequently for 5 days). Body weight, food intake, and fecal pH were recorded. Intestinal tissue samples were collected 1 day after the end of TMZ treatment. Degree of damage to intestine, expression of IL1ß, IL6, TNFα, and IL10 in jejunum were determined. Levels of tight-junction proteins (ZO1, occludin), TLR4, IKKß, IκBα, and P65 with their phosphorylation in jejunum were measured. Results: Decreases in body weight, food intake, spleen index in the TMZ group were mitigated in the LGG+TMZ group, and the degree of intestinal shortening and damage to jejunum villus were also alleviated. The expression of tight-junction proteins in the LGG+TMZ group was significantly greater than that in the TMZ group. IκBα in intestinal tissue significantly decreased in the TMZ group, phos-IKKß and phos-P65 increased compared to the CON group, and LGG reversed such changes in IκBα and phos-P65 in the LGG+TMZ group. Intestinal inflammatory cytokines were significantly increased in the TMZ group, but lower in the LGG+TMZ group. Moreover, expression of TLR4 in LGG group was significantly lower than that in the CON group. LGG inhibited the rise of TLR4 after TMZ in the LGG+TMZ group compared to the TMZ group. Conclusion: LGG inhibits the activation of the TLR4-NFκB pathway and alleviates intestinal mucosal inflammation induced by TMZ, thereby protect the jejunum villi and mucosal physical barrier.

Effects of Electroacupuncture for Opioid-Induced Constipation in Patients With Cancer in China: A Randomized Clinical Trial.

Importance: Opioid-induced constipation (OIC) is prevalent among patients treated with opioids for cancer pain. Safe and effective therapies for OIC in patients with cancer remain an unmet need. Objective: To determine the efficacy of electroacupuncture (EA) for OIC in patients with cancer. Design, Setting, and Participants: This randomized clinical trial was conducted at 6 tertiary hospitals in China among 100 adult patients with cancer who were screened for OIC and enrolled between May 1, 2019, and December 11, 2021. Interventions: Patients were randomized to receive 24 sessions of EA or sham electroacupuncture (SA) over 8 weeks and then were followed up for 8 weeks after treatment. Main Outcomes and Measures: The primary outcome was the proportion of overall responders, defined as patients who had at least 3 spontaneous bowel movements (SBMs) per week and an increase of at least 1 SBM from baseline in the same week for at least 6 of the 8 weeks of the treatment period. All statistical analyses were based on the intention-to-treat principle. Results: A total of 100 patients (mean [SD] age, 64.4 [10.5] years; 56 men [56.0%]) underwent randomization; 50 were randomly assigned to each group. Among them, 44 of 50 patients (88.0%) in the EA group and 42 of 50 patients (84.0%) in the SA group received at least 20 (≥83.3%) sessions of treatment. The proportion of overall responders at week 8 was 40.1% (95% CI, 26.1%-54.1%) in the EA group and 9.0% (95% CI, 0.5%-17.4%) in the SA group (difference between groups, 31.1 percentage points [95% CI, 14.8-47.6 percentage points]; P < .001). Compared with SA, EA provided greater relief for most OIC symptoms and improved quality of life among patients with OIC. Electroacupuncture had no effects on cancer pain and its opioid treatment dosage. Electroacupuncture-related adverse events were rare, and, if any, all were mild and transient. Conclusions and Relevance: This randomized clinical trial found that 8-week EA treatment could increase weekly SBMs with a good safety profile and improve quality of life for the treatment of OIC. Electroacupuncture thus provided an alternative option for OIC in adult patients with cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03797586.

Clinical significance and molecular annotation of cellular morphometric subtypes in lower-grade gliomas discovered by machine learning.

BACKGROUND: Lower-grade gliomas (LGG) are heterogeneous diseases by clinical, histological, and molecular criteria. We aimed to personalize the diagnosis and therapy of LGG patients by developing and validating robust cellular morphometric subtypes (CMS) and to uncover the molecular signatures underlying these subtypes. METHODS: Cellular morphometric biomarkers (CMBs) were identified with artificial intelligence technique from TCGA-LGG cohort. Consensus clustering was used to define CMS. Survival analysis was performed to assess the clinical impact of CMBs and CMS. A nomogram was constructed to predict 3- and 5-year overall survival (OS) of LGG patients. Tumor mutational burden (TMB) and immune cell infiltration between subtypes were analyzed using the Mann-Whitney U test. The double-blinded validation for important immunotherapy-related biomarkers was executed using immunohistochemistry (IHC). RESULTS: We developed a machine learning (ML) pipeline to extract CMBs from whole-slide images of tissue histology; identifying and externally validating robust CMS of LGGs in multicenter cohorts. The subtypes had independent predicted OS across all three independent cohorts. In the TCGA-LGG cohort, patients within the poor-prognosis subtype responded poorly to primary and follow-up therapies. LGGs within the poor-prognosis subtype were characterized by high mutational burden, high frequencies of copy number alterations, and high levels of tumor-infiltrating lymphocytes and immune checkpoint genes. Higher levels of PD-1/PD-L1/CTLA-4 were confirmed by IHC staining. In addition, the subtypes learned from LGG demonstrate translational impact on glioblastoma (GBM). CONCLUSIONS: We developed and validated a framework (CMS-ML) for CMS discovery in LGG associated with specific molecular alterations, immune microenvironment, prognosis, and treatment response.

Public knowledge and attitudes toward automated external defibrillators use among first aid eLearning course participants: a survey.

OBJECTIVE: Survival from out-of-hospital cardiac arrest (OHCA) often depends on the effective and immediate use of automated external defibrillators (AEDs). Given that there have been few studies about AED use in China, the purpose of this study is to investigate the knowledge and attitudes regarding AED use among the Chinese public, then provide an effective suggestion for AED education strategies and legislation. METHOD: The online survey was conducted among Chinese participants of the First Aid eLearning courses in June 2020. RESULT: A total of 2565 (95.00%) surveys were completed, only 23.46% of respondents with non-medical related respondents reported having attended previous AED training courses. Regarding the basic knowledge of AEDs, few respondents (12.28%, n = 315) could answer all four questions correctly. 95.67% (n = 2454) were willing to learn AED use. Even if without the precondition of being skilled in AEDs, the female was more likely to rescue OHCA patients than the male (p = 0.003). Almost all respondents (96.65%) showed a strong willingness to rescue OHCA patients with training in using AEDs. The top four barriers to rescuing OHCA patients were lack of practical performing ability (60.47%), fear of hurting patients (59.30%), inadequate knowledge of resuscitation techniques (44.19%), and worry about taking legal responsibility (26.74%). CONCLUSION: Our study reflects a deficiency of AED knowledge among the general public in China. However, positive attitudes towards rescuing OHCA patients and learning AED use were observed, which indicates that measures need to be taken to disseminate knowledge and use of AEDs.

1ß-Hydroxyalantolactone from Inulae Flos alleviated the progression of pulmonary fibrosis via inhibiting JNK/FOXO1/NF-κB pathway.

Inulae Flos was widely distributed throughout Europe, Africa, and Asia, and was commonly used as a folk medicine in clinic for treating various respiratory diseases, including cough, asthma, bronchitis, pulmonary fibrosis, and pneumonia. However, the ingredients responsible for the pharmacology effects of I. Flos and the underlying mechanisms remain unclear. In this study, the effects of 16 known sesquiterpene lactones and flavonoids from I. Flos on TGF-ß1-induced fibroblast activation were assessed by phenotypic high-content screening. Among those sixteen compounds, 1ß-hydroxy alantolactone (HAL), the main characteristic sesquiterpene lactone from I. Flos, exhibited remarkable inhibitory activity. The further studies showed that HAL significantly inhibited the proliferation and induced the apoptosis of human fibroblast cell lines HELF and MRC-5 in a concentration-dependent manner. It also reduced intracellular ROS production, suppressed the mRNA expressions of E-cad, TGF-ß1, Smad3, Col I, α-SMA and TNF-α, and downregulated protein expressions of α-SMA and F-actin. Furthermore, HAL significantly reduced the levels of HA, LN, PC-III and IV-C in serum, TNF-α and IL-6 in BALF, and TGF-ß1, HYP and Col I in lung tissues of bleomycin (BLM)-treated rats. HAL significantly downregulated the expressions of p-JNK, FOXO1, p-p65, α-SMA, p-smad3 and Col I but upregulated p-FOXO1, which could be reversed by JNK agonist anisomycin. These results demonstrated that HAL induced the apoptosis of lung fibroblast cells activated by TGF-ß1 and improved BLM-induced lung fibrosis in rats via inhibiting JNK/FOXO1/NF-κB pathway.

A prognostic scoring system for operated acute epidural hematoma based on gray-white matter ratio.

ABSTRACT: To determine the prognostic risk factors of patients with acute epidural hematoma (AEDH), a scoring system was established based on gray-white matter ratio (GWR) and internal verification was performed.All patients with AEDH who underwent surgical treatment in Qinghai Provincial People's Hospital from January 2013 to June 2019 were continuously collected. The clinical and imaging data of the patients were collected. According to Glasgow Outcome Scale at 3 months after operation, the patients were divided into poor and good prognosis groups, respectively. The GWR value of the nonhematoma side was measured at the inner capsule area. Univariate and multivariate analyses were used. Independent predictors significantly related to the prognosis of AEDH were screened out and a nomogram was established based on these factors.A total of 170 cases were included in this study, the Glasgow Coma Score (severe and moderate), cerebral hernia, midline shift, preoperative GWR, postoperative GWR, hematoma thickness/midline shift, time from coma to surgery, and decompression of bone flap were the independent risk factors for predicting the poor prognosis of AEDH. Moreover, the prediction ability of nomogram was higher than any other independent predictive factors.The nomogram model established represents the most effective factor to predict the prognosis of operated AEDH. The scoring system is characterized by high accuracy, simplicity and feasibility, with a wide range of clinical application prospects.

Temozolomide-Induced Changes in Gut Microbial Composition in a Mouse Model of Brain Glioma.

BACKGROUND: Gut microbiota is associated with the progression of brain tumors. However, the alterations in gut microbiota observed during glioma growth and temozolomide (TMZ) therapy remain poorly understood. METHODS: C57BL/6 male mice were implanted with GL261 glioma cells. TMZ/sodium carboxymethyl cellulose (SCC) was administered through gavage for five consecutive days (from 8 to 12 days after implantation). Fecal samples were collected before (T0) and on days 7 (T1), 14 (T2), and 28 (T3) after implantation. The gut microbiota was analyzed using 16S ribosomal DNA sequencing followed by absolute and relative quantitation analyses. RESULTS: Nineteen genera were altered during glioma progression with the most dramatic changes in Firmicutes and Bacteroidetes phyla. During glioma growth, Lactobacillus abundance decreased in the early stage (T1) and then gradually increased (T2, T3); Intestinimonas abundance exhibited a persistent increase; Anaerotruncus showed a transient increase (T2) and then a subsequent decrease (T3). Similar longitudinal changes in Intestinimonas and Anaerotruncus abundance were observed in TMZ-treated mice, but the decrease of Anaerotruncus at T3 in the TMZ-treated group was less than that in the vehicle-treated group. No significant change in Lactobacillus was observed after TMZ treatment. Additionally, compared to vehicle control, TMZ treatment led to an enrichment in Akkermansia and Bifidobacterium. CONCLUSION: Glioma development and progression altered the composition of gut microbiota. Induction of Akkermansia and Bifidobacterium as well as the prevention of the reduction in Anaerotruncus may contribute to the anti-tumor effect of TMZ. This study helps to reveal the association between levels of specific microbial species in the gut and the anti-tumor effect of TMZ.

[Ginger-separated moxibustion for chronic fatigue syndrome and its effect on intestinal flora].

OBJECTIVE: To observe the effect of ginger-separated moxibustion on fatigue state and intestinal flora in patients with chronic fatigue syndrome (CFS). METHODS: A total of 62 patients with CFS were randomly divided into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). The patients in the control group were treated with normal diet and moderate exercise; on the basis of the control group, the patients in the observation group were treated with ginger-separated moxibustion at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every other day, three times a week. Both groups were intervened for 4 weeks. Before and after treatment, the fatigue scale-14 (FS-14) was used to observe the improvement of fatigue state, and 16S rRNA detection technology was used to detect the distribution of intestinal flora. RESULTS: Compared before treatment, the FS-14 score was reduced after treatment in the observation group (P<0.01), and the reduction in the observation group was larger than that in the control group (P<0.01). The relative abundance of intestinal flora was similar between the observation group and control group at the phylum and genus level before treatment. After treatment, there was no significant change of intestinal flora in the control group. However, the enterobacteriaceae, corynebacterium, erysipelothrix, actinomycetes were increased in the observation group (P<0.05), and actinomycetes, ruminococcus, lactarius had obvious flora advantages compared with the control group (P<0.05). CONCLUSION: The ginger-separated moxibustion could significantly improve the fatigue state in CFS patients, which may be related to the regulation of intestinal flora structure and the repair of intestinal barrier.

[Effect of ginger-separated moxibustion on fatigue, sleep quality and depression in patients with chronic fatigue syndrome: a randomized controlled trial].

OBJECTIVE: To observe the effect of ginger-separated moxibustion on fatigue, sleep quality and depression in the patients with chronic fatigue syndrome. METHODS: A total of 62 patients with chronic fatigue syndrome were randomized into an observation group (31 cases, 3 cases dropped off) and a control group (31 cases, 2 cases dropped off). In the control group, the patients had normal diet and proper physical exercise. In the observation group, on the basis of the control group, the ginger-separated moxibustion was added at Zhongwan (CV 12), Shenque (CV 8) and Guanyuan (CV 4), 30 min each time, once every two days, 3 times weekly. Separately, before treatment and after 4 weeks of treatment, the MOS item short form health survey (SF-36), the Pittsburgh sleep quality index (PSQI) scale and the self-rating depression scale (SDS) were adopted to evaluate the degrees of fatigue, sleep quality and depression in the patients of the two groups. RESULTS: In the observation group, the score of each item of SF-36, the score of each item of PSQI and SDS score after treatment were all improved significantly as compared with those before treatment respectively (P<0.05, P<0.01). In the control group, the scores of overall health, vitality and mental health in SF-36 and the score of sleep time of PSQI after treatment were improved as compared with those before treatment respectively (P<0.05). After treatment, the score of each item of SF-36, the scores of sleep quality, sleep time, sleep efficiency and sleep disorders of PSQI, as well as SDS score in the observation group were all better than those in the control group respectively (P<0.01, P<0.05). The score of SF-36 was relevant to the scores of PSQI and SDS in the patients of chronic fatigue syndrome (r =0.331, P<0.05; r =-0.706, P<0.01). The improvement value of SF-36 score was closely related to the improvement value of SDS score in the observation group (r =-0.657, P<0.01). CONCLUSION: The ginger-separated moxibustion effectively relieves fatigue and depression condition and improves sleep quality in the patients with chronic fatigue syndrome. The fatigue condition is relevant with sleep quality and depression condition to a certain extent in the patients.

Study of cardiovascular disease prediction model based on random forest in eastern China.

Cardiovascular disease (CVD) is the leading cause of death worldwide and a major public health concern. CVD prediction is one of the most effective measures for CVD control. In this study, 29930 subjects with high-risk of CVD were selected from 101056 people in 2014, regular follow-up was conducted using electronic health record system. Logistic regression analysis showed that nearly 30 indicators were related to CVD, including male, old age, family income, smoking, drinking, obesity, excessive waist circumference, abnormal cholesterol, abnormal low-density lipoprotein, abnormal fasting blood glucose and else. Several methods were used to build prediction model including multivariate regression model, classification and regression tree (CART), Naïve Bayes, Bagged trees, Ada Boost and Random Forest. We used the multivariate regression model as a benchmark for performance evaluation (Area under the curve, AUC = 0.7143). The results showed that the Random Forest was superior to other methods with an AUC of 0.787 and achieved a significant improvement over the benchmark. We provided a CVD prediction model for 3-year risk assessment of CVD. It was based on a large population with high risk of CVD in eastern China using Random Forest algorithm, which would provide reference for the work of CVD prediction and treatment in China.

Epitranscriptomic profiling of N6-methyladenosine-related RNA methylation in rat cerebral cortex following traumatic brain injury.

BACKGROUND: N6-methyladenosine (m6A) is the most prevalent post-transcriptional modification of eukaryotic mRNA. It has been reported that there is a stimulus-dependent regulation of m6A in the mammalian central nervous system in response to sensory experience, learning, and injury. The mRNA m6A methylation pattern in rat cortex after traumatic brain injury (TBI) has not been investigated. RESULTS: In this study, we conducted a genome-wide profiling of mRNA m6A methylation in rat cortex via methylated RNA immunoprecipitation sequencing (MeRIP-Seq). After TBI, the expressions of METTL14 and FTO were significantly down-regulated in rat cerebral cortex. Using MeRIP-Seq, we identified a total of 2165 significantly changed peaks, of which 1062 were significantly up-regulated and 1103 peaks were significantly down-regulated. These m6A peaks were located across 1850 genes. The analysis of both m6A peaks and mRNA expression revealed that there were 175 mRNA significantly altered methylation and expression levels after TBI. Moreover, it was found that functional FTO is necessary to repair neurological damage caused by TBI but has no effect on the spatial learning and memory abilities of TBI rats by using FTO inhibitor FB23-2. CONCLUSION: This study explored the m6A methylation pattern of mRNA after TBI in rat cortex and identified FTO as possible intervention targets in the epigenetic modification of TBI.

Comparison of prevalence and associated risk factors of cognitive function status among elderly between nursing homes and common communities of China: A STROBE-compliant observational study.

Dementia among elderly is a serious problem worldwide. This study was conducted to estimate the prevalence and associated risk factors of dementia and mild cognitive impairment (MCI) in nursing homes (NHs) and common communities (CCs) among elderly in China.A cross-sectional survey was conducted in 4 communities across 12 cities in Southern China from May to November of 2014. Qualified psychiatrists and trained nurses carried out relevant diagnosis, assessments, interviews, and information collection. Screening test of mini-mental state examination was conducted among participants firstly, then confirmed diagnosis was carried out among the ones with positive results. Student t test, χ test, univariate, and multivariate logistic regression analysis were conducted to analyze data.A total of 2015 participants aged 65 or older were included in the final analysis; 908 came from NHs while 1107 came from CCs. The crude prevalence rates of dementia and MCI were 22.0% and 15.8%, respectively among all the participants. Dementia prevalence was 42.4% among those living in NHs, which was significantly higher than that of 5.3% in CCs (P < .0001). There were more moderate and severe dementia in NHs compared with CCs (P < .0001). It showed that older age, illiterate compared with high level of education (adjusted odds ratio, AOR = 3.32, 95% CI: 1.53-7.21), heavy drinking (AOR = 1.51 (1.00-2.24), having a medical history of diabetes (AOR = 1.41, 95% CI: 1.02-2.33), and stroke (AOR = 1.21, 95% CI: 1.01-1.23) were associated with dementia in NHs, and middle socioeconomic status might be a protective factor for dementia (AOR = 0.33, 95% CI: 0.21-0.51).The problem of senile dementia in NHs is much more serious than our estimation, and there are not enough trained nursing staffs in NHs. More population-based strategies in NHs, including conducting cognitive screening accompanied with routine physical examination among elderly population, carrying out related primary prevention policies and public health services, and paying attention to some modifiable associated risk factors such as heavy smoking and drinking are needed.

1,25-Vitamin D3 protects against cooking oil fumes-derived PM2.5-induced cell damage through its anti-inflammatory effects in cardiomyocytes.

The functional role of 1,25-vitamin D3 in cooking oil fumes (COFs)-derived PM2.5-induced cell damage is largely unexplored. The present study investigated the protective role of 1,25-vitamin D3 against cell injury by possible involvement of JAK/STAT and NF-κB signaling pathways in cardiomyocytes. Cell viability was measured using CCK-8 assay, and cell apoptosis was analyzed by flow cytometry, qRT-PCR and Western blot in cultured rat neonatal cardiomyocytes treated with 1,25-vitamin D3 and COFs-derived PM2.5. Expressions of JAK/STAT and NF-κB signaling pathway were measured by Western blot. The results suggested that treatment with COFs-derived PM2.5 significantly decreased cell viability and increased apoptosis and oxidative stress in cultured rat neonatal cardiomyocytes. 1,25-vitamin D3 pretreatment alleviated the cell injury by increasing cell viability and decreasing apoptosis in the cardiomyocytes. 1,25-vitamin D3 pretreatment also decreased the ROS level and inflammation in the cardiomyocytes. Furthermore, 1,25-vitamin D3 pretreatment alleviated COFs-derived PM2.5-evoked elevation of JAK/STAT and NF-κB signaling pathways. Our study showed that 1,25-vitamin D3 pretreatment protected cardiomyocytes from COFs-derived PM2.5-induced injury by decreasing ROS, apoptosis and inflammation level via activations of the JAK/STAT and NF-κB signaling pathways.

Screening for Dementia in Older Adults: Comparison of Mini-Mental State Examination, Mini-Cog, Clock Drawing Test and AD8.

This study was conducted to estimate screening performance of dementia screening tools including Mini-Mental State Examination (MMSE), Mini-Cog, Clock Drawing Test (CDT) and Ascertain Dementia 8 questionnaire (AD8) for older adults. 2015 participants aged 65 years or more in eastern China were enrolled. 4 screening tests were administered and scored by specifically trained psychiatrists. We used data from two-by-two tables to calculate the sensitivity, specificity, and positive and negative predictive values (PPV/NPV). Our study showed that dementia was highly prevalent among elderly in Zhejiang province. The Mini-Cog, with excellent screening characteristics and spending less time, could be considered to be used as a screening tool among communities to help to diagnose dementia early.

Prevalence of dementia, cognitive status and associated risk factors among elderly of Zhejiang province, China in 2014.

BACKGROUND: the prevalence of dementia in China has risen dramatically in recent decades, but it is not well understood the status in the elderly population in Zhejiang province, eastern China. METHODS: a cross-sectional survey was conducted in four communities across 12 counties in Zhejiang province from May to November 2014. Recruitment included 2,015 subjects aged 65 or older. Trained assessors performed assessments and interviews and collected information. Dementia was diagnosed according to the NIA-AA criteria in 2011. RESULTS: the age-gender-standardised prevalence rates of dementia, Alzheimer's disease and vascular dementia were 13.0, 6.9 and 0.5%, respectively. There were significant increasing trends of rates over ages. Elderly, low educational level, heavy smoking, heavy alcohol consumption, diabetes and stroke were associated with dementia; tea consumption was associated with low prevalence of Alzheimer's disease and severe cognitive impairment. CONCLUSIONS: dementia and cognitive impairment were relatively high among the elderly in Zhejiang province; more attention and population-based strategies are needed.

Studies on the formation and synthetic mechanism of related substance G in potassium clavulanate production

The objective of this study was to investigate the formation and synthetic mechanism of related substance G in potassium clavulanate production. The impurity in the potassium clavulanate final product, with a retention time of 13.5 min, was confirmed as related substance G by high performance liquid chromatography-mass spectrometry/mass spectrometry. Related substance G analysis during the production of clavulanic acid showed that this impurity could be synthesized during fermentation, and the amount increased with the fermentation time. Studies on its synthetic mechanism showed that L-tyrosine and succinic acid were the precursors for biosynthesis of related substance G in vivo. The reaction was deduced to be catalyzed by an enzyme. The enzyme was a type of extracellular enzyme present in the fermentation supernatant.

O objetivo deste estudo foi investigar a formação e o mecanismo sintético da substância G relacionada na produção de clavulanato de potássio. A impureza do produto final clavulanato de potássio, com tempo de retenção de 13,5 min, foi confirmada como substância G relacionada por cromatografia líquida de alta eficiência-espectrometria de massas/espectrometria de massas. A análise da substância G relacionada durante a produção do ácido clavulânico mostrou que essa impureza poderia ser sintetizada durante a fermentação e que a quantidade aumenta com o tempo de fermentação. Estudos do seu mecanismo sintético mostraram que a L-tirosina e o ácido succínico foram os precursores in vivo para a biossíntese da substância G relacionada. Deduziu-se que a reação foi catalisada por uma enzima. A enzima foi do tipo extracelular, presente no sobrenadante da fermentação.

Studies on the formation and forming mechanism of the related substance E in potassium clavulanate production by HPLC-MS/MS

The objective of this study was to investigate the formation and forming mechanism of the related substance E in potassium clavulanate production. The impurity with retention time of 11.1 min in potassium clavulanate final product was confirmed as the related substance E by high performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS).The related substance E analysis during the production of clavulanic acid showed that this impurity could be formed during both the fermentation and purification processes, especially in the later fermentation stage, filtration concentration and back-extraction procedure. Clavulanic acid was the precursor of the related substance E. Studies on its forming mechanism showed that the related substance E was formed by the combination of the imino group of one molecule of clavulanic acid with the carboxyl group of another molecule of clavulanic acid with the opening of β-lactam ring. Results of a multi-factor orthogonal test confirmed that the concentration of clavulanic acid was the dominant factor to accelerate the reaction, while the temperature was another contributing factor. The pH 5.0-6.5 had little impact on the generation of the related substance E.

O objetivo deste estudo foi investigar a formação da substância E e o respectivo mecanismo na produção de clavulanato de potássio. Confirmou-se a impureza com tempo de retenção de 11,1 min no produto final, clavulanato de potássio, como substância E, por meio de cromatografia líquida de alta eficiência, em conjunto com detecção por espectrometria de massas (CLAE-MS-MS). A análise da substância relacionada E durante a produção do ácido clavulânico mostrou que essa impureza pode ser formada tanto durante a fermentação quanto durante os processos de purificação, especialmente no estágio final de fermentação, filtração, concentração e procedimento de extração. O ácido clavulãnico foi o precursor da substância E. Estudos no mecanismo de sua formação mostraram que a substância E formou-se pela combinação do grupo imina da molécula do ácido clavulânico com o grupo carboxílico de outra molécula de ácido clavulânico, com a abertura do anel β-lactâmico. Resultados do teste ortogonal multifatorial confirmaram que a concentração do ácido clavulânico foi o fator dominante para acelerar a reação, enquanto a temperatura foi outro fator que contribuiu. O pH de 5,0 a 6,5 teve pouco impacto na geração da substância E.