Prunolactones A-G, proangiogenic isocoumarin derivatives with an unusual 6/6/6/6/6 spiropentacyclic skeleton from the endophytic fungus Phomopsis prunorum.

Seven novel isocoumarins, prunolactones A-G (1-7), featuring an unusual 6/6/6/6/6 spiropentacyclic skeleton, together with two biosynthetic precursors phomopsilactone (8) and methyl 3-epi-shikimate (9), were isolated from the endophytic fungus Phomopsis prunorum guided by UPLC-QTOF-MS and 1H NMR spectroscopic analytical techniques. Their structures including absolute configurations of 1-7 were elucidated based on extensive spectroscopic data, X-ray diffraction analysis, and ECD calculations. Biogenetically, compounds 1-7 are proposed to be derived from polyketide and shikimate pathways via key intermolecular Diels - Alder reactions. Compounds 2, 3, and 7 showed significant in vivo proangiogenic activity in transgenic zebrafish.

Helicobacter pylori infection is associated with reduced risk of Barrett's esophagus: a meta-analysis and systematic review.

BACKGROUND: Helicobacter pylori (Hp) is a class I carcinogen in gastric carcinogenesis, but its role in Barrett's esophagus (BE) is unknown. Therefore, we aimed to explore the possible relationship. METHODS: We reviewed observational studies published in English until October 2019. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for included studies. RESULTS: 46 studies from 1505 potential citations were eligible for inclusion. A significant inverse relationship with considerable heterogeneity was found between Hp (OR = 0.70; 95% CI, 0.51-0.96; P = 0.03) and BE, especially the CagA-positive Hp strain (OR = 0.28; 95% CI, 0.15-0.54; P = 0.0002). However, Hp infection prevalence was not significantly different between patients with BE and the gastroesophageal reflux disease (GERD) control (OR = 0.99; 95% CI, 0.82-1.19; P = 0.92). Hp was negatively correlated with long-segment BE (OR = 0.47; 95% CI, 0.25-0.90; P = 0.02) and associated with a reduced risk of dysplasia. However, Hp had no correlated with short-segment BE (OR = 1.11; 95% CI, 0.78-1.56; P = 0.57). In the present infected subgroup, Hp infection prevalence in BE was significantly lower than that in controls (OR = 0.69; 95% CI, 0.54-0.89; P = 0.005); however, this disappeared in the infection history subgroup (OR = 0.88; 95% CI, 0.43-1.78; P = 0.73). CONCLUSIONS: Hp, especially the CagA-positive Hp strain, and BE are inversely related with considerable heterogeneity, which is likely mediated by a decrease in GERD prevalence, although this is not observed in the absence of current Hp infection.

Effects of inhalation and propofol anaesthesia on postoperative cognitive dysfunction in elderly noncardiac surgical patients: A systematic review and meta-analysis.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a very common event in elderly noncardiac surgical patients. The effects of inhalational anaesthetics and propofol on the incidence of POCD and postoperative cognitive status at different time points after surgery are currently unclear. METHODS: We searched the Embase, Medline, Cochrane Library, and Web of Science databases for randomized controlled trials (RCTs), in which inhalation anaesthesia and propofol anaesthesia were compared. The incidence of POCD or postoperative cognitive status was assessed in elderly patients undergoing noncardiac surgery. RESULTS: Fifteen RCTs with 1854 patients were included in this meta-analysis. The incidence of POCD on postoperative Days 2-6 after propofol anaesthesia was markedly lower than that after inhalation anaesthesia (risk ratio (RR): 0.37, 95% confidence interval (CI): 0.15-0.88, P = .025), and Mini-Mental State Examination (MMSE) scores after propofol anaesthesia were substantially higher than those after inhalation anaesthesia (standard mean difference (SMD): 0.59, 95% CI: 0.07-1.11, P = .026). The levels of interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) were much lower after propofol anaesthesia than after inhalation anaesthesia (SMD: -2.027, 95% CI: -3.748- -0.307, P = .021; SMD: -0.68, 95% CI: -0.93- -0.43, P < .001). CONCLUSIONS: The moderate evidence from this meta-analysis shows that, in elderly noncardiac surgical patients, propofol anaesthesia is superior to inhalation anaesthesia for attenuating of early POCD incidence, and low-level evidence shows that cognitive status is higher and systemic inflammation is less severe after propofol anaesthesia in the early days after surgery. LIMITATIONS: The sample size was not sufficiently large for systemic inflammation, and the tools to identify POCD were not uniform in the included studies.

Comparison of Outcomes After Breast Cancer Surgery Between Inhalational and Propofol-Based Intravenous Anaesthesia: A Systematic Review and Meta-Analysis.

BACKGROUND: General anaesthesia is the commonly provided for breast cancer surgery, but the effects of inhalational anaesthesia and propofol-based intravenous anaesthesia on short- and long-term outcomes after breast cancer surgery are not clear. In this study, we conduct a meta-analysis of randomized controlled trials (RCTs) to explore the superior anaesthetic for breast cancer surgery patients. METHODS: We searched the Embase, Medline, Cochrane Library, Web of Science, CNKI, and Wanfang databases (up to January, 2021) for RCTs in which inhalational anaesthesia and propofol-based intravenous anaesthesia were compared and short- and long-term outcomes were assessed in breast cancer surgical patients. The meta-analysis was performed by Stata 12.0. RESULTS: Twenty RCTs with a total of 2201 patients were included. Compared with inhalational anaesthesia, propofol-based intravenous anaesthesia was associated with more postoperative rescue analgesia (I2 =0%, RR: 1.18, 95% CI: 1.07-1.30, P=0.001) but a lower incidence of postoperative nausea and vomiting (PONV) (I2 =25.5%, RR: 0.71, 95% CI: 0.62-0.81, P<0.001) and postoperative rescue antiemetics (I2 =0%, RR: 0.69, 95% CI: 0.58-0.82, P<0.001). Propofol-based intravenous anaesthesia preserved nature killer cell cytotoxicity (I2 =86.2%, SMD: 0.76, 95% CI: 0.13-1.39, P=0.018), decreased IL-6 level (I2 =98.0%, SMD: -3.09, 95% CI: -5.70- -0.48, P=0.021) and neutrophil-to-lymphocyte ratio (I2 =0%, SMD: -0.28, 95% CI: -0.53- -0.03, P=0.030), and increased 2-year recurrence-free survival rate (I2 =0%, RR: 1.10, 95% CI: 1.00-1.20, P=0.043) but did not affect recurrence or the overall survival rate (P>0.05). CONCLUSION: Propofol-based intravenous anaesthesia increases postoperative rescue analgesia but reduces PONV compared with inhalational anaesthesia in breast cancer surgery. The benefit of propofol over inhalational anaesthetics in the preservation of anti-cancer immunity is obvious, but it is difficult to conclude that propofol can exert long-term benefits due to the small sample size.

Epidemiological and clinical features of functional dyspepsia in a region with a high incidence of esophageal cancer in China.

BACKGROUND: Functional dyspepsia (FD) has rarely been investigated in areas with a high prevalence of esophageal squamous cell carcinoma (ESCC). This study aims to reveal the epidemiological and clinical features of FD and organic dyspepsia (OD) in such a population. METHODS: A middle-aged and elderly population-based study was conducted in a region with a high incidence of ESCC. All participants completed the Gastroesophageal Reflux Disease Questionnaire and Functional Gastrointestinal Disease Rome III Diagnostic Questionnaire, and they underwent gastroscopy. After exclusion of gastroesophageal reflux disease, uninvestigated dyspepsia (UID) was divided into OD and FD for further analyses. RESULTS: A total of 2916 participants were enrolled from July 2013 to March 2014 in China. We detected 166 UID cases with questionnaires, in which 17 patients with OD and 149 with FD were diagnosed via gastroscopy. OD cases presented as reflux esophagitis (RE), ESCC, and duodenal ulcer. Heartburn (52.94%) and reflux (29.41%) were common in OD, but no symptomatic differences were found between FD and OD. Male sex, low education level, and liquid food were the risk factors for OD, while frequent fresh vegetable consumption was a protective factor. FD included 56 (37.58%) cases of postprandial distress syndrome (PDS), 52 (34.89%) of epigastric pain syndrome (EPS), nine (6.04%) of PDS + EPS, and 32 (21.48%) of FD + functional esophageal disorders. The Helicobacter pylori infection rate in FD patients was not higher than that in the control group (34.23% vs. 42.26%, P = 0.240). Frequent spicy food consumption was associated with PDS (odds ratio [OR]: 2.088, 95% confidence interval [CI]: 1.028-4.243), while consumption of deep well water was protective for PDS (OR: 0.431, 95% CI: 0.251-0.741). CONCLUSIONS: The prevalence of FD was 5.11% in the studied population. Gastroscopy should be prescribed for dyspepsia patients in case that ESCC and RE would be missed in UID cases diagnosed solely by the Rome III questionnaire. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01688908; https://clinicaltrials.gov/ct2/show/record/NCT01688908.

Sex-based differences in fecal short-chain fatty acid and gut microbiota in irritable bowel syndrome patients.

OBJECTIVE: To explore alterations in fecal short-chain fatty acids (SCFA) and gut microbiota in patients with diarrhea-predominant irritable bowel disease (IBS-D) and their relationships with clinical manifestations. METHODS: We recruited 162 patients with IBS-D and 66 healthy controls (HC). Their manifestations and psychological status were evaluated using the IBS severity scoring system and the Hospital Anxiety and Depression Scale (HADS). Colorectal visceral sensitivity was evaluated using a barostat. Systemic inflammation was evaluated using plasma cytokine levels. Fecal SCFA were quantified using ultra-performance liquid chromatography-tandem mass spectrometry, and fecal microbiota communities were analyzed using 16S rRNA sequencing. RESULTS: More men presented with IBS-D than women in our patient cohort. Patients with IBS-D had more severe manifestations, higher HADS score, and a higher rate of previous infectious enteritis than HC. Notably, female patients had significantly higher HADS scores than male patients. Male patients had significantly higher levels of plasma interleukin (IL)-12, fecal propionate and colorectal visceral sensitivity than male HC, while no differences were observed between female patients and female HC. Fecal acetate, butyrate and valerate correlated with the initial visceral sensory threshold, stressors, and IL-10 and IL-12 levels. The propionate-producing Prevotella 9 genus was significantly increased in male patients and positively correlated with fecal propionate. CONCLUSION: Distinct sex-based differences in clinical manifestations, fecal SCFA and microbiota richness are found in Chinese patients with IBS-D, which may be used to diagnose dysbiosis in these patients.

Berberine alleviates visceral hypersensitivity in rats by altering gut microbiome and suppressing spinal microglial activation.

Accumulating evidence shows that agents targeting gut dysbiosis are effective for improving symptoms of irritable bowel syndrome (IBS). However, the potential mechanisms remain unclear. In this study we investigated the effects of berberine on the microbiota-gut-brain axis in two rat models of visceral hypersensitivity, i.e., specific pathogen-free SD rats subjected to chronic water avoidance stress (WAS) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 10 days) as well as germ-free (GF) rats subjected to fecal microbiota transplantation (FMT) from a patient with IBS (designated IBS-FMT) and treated with berberine (200 mg· kg-1 ·d-1, ig, for 2 weeks). Before the rats were sacrificed, visceral sensation and depressive behaviors were evaluated. Then colonic tryptase was measured and microglial activation in the dorsal lumbar spinal cord was assessed. The fecal microbiota was profiled using 16S rRNA sequencing, and short chain fatty acids (SCFAs) were measured. We showed that berberine treatment significantly alleviated chronic WAS-induced visceral hypersensitivity and activation of colonic mast cells and microglia in the dorsal lumbar spinal cord. Transfer of fecal samples from berberine-treated stressed donors to GF rats protected against acute WAS. FMT from a patient with IBS induced visceral hypersensitivity and pro-inflammatory phenotype in microglia, while berberine treatment reversed the microglial activation and altered microbial composition and function and SCFA profiles in stools of IBS-FMT rats. We demonstrated that berberine did not directly influence LPS-induced microglial activation in vitro. In both models, several SCFA-producing genera were enriched by berberine treatment, and positively correlated to the morphological parameters of microglia. In conclusion, activation of microglia in the dorsal lumbar spinal cord was involved in the pathogenesis of IBS caused by dysregulation of the microbiota-gut-brain axis, and the berberine-altered gut microbiome mediated the modulatory effects of the agent on microglial activation and visceral hypersensitivity, providing a potential option for the treatment of IBS.

[Progresses on the effects and mechanisms of stress on gut microbiota].

Stress is the non-specific systemic response that occurs when the body is stimulated by various factors, and it can affect multiple systems of the body. Recent studies have shown that gut microbiota is an essential part of human microecology, and plays a pivotal role in keeping the body healthy. Stress can result in gut dysbiosis by affecting the function of intestinal mucosal barrier, intestinal immune and gastrointestinal motility. This article reviewed the alteration of gut microbiota caused by stress and the possible mechanisms involved.

Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.

Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.

Depression at Baseline Is an Independent Risk Factor for Cognitive Decline in Patients on Peritoneal Dialysis: A Multicenter Prospective Cohort Study.

Background:Depression has been recognized as a risk factor for cognitive impairment (CI) from cross-sectional datasets. This multicenter prospective study investigated the association between depression and cognitive decline in peritoneal dialysis (PD) patients.Methods:This multicenter prospective cohort study included 458 PD patients who were followed up for 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function, Trail-Making Tests A and B for executive function, subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skill, and language ability. Depression was assessed using Zung's Self-Rating Depression Scale.Results:During the 2-year follow-up, patients with moderate/severe depression at baseline showed a significant decline in global cognitive function (80.5 ± 15.2 vs 76.6 ± 15.5, p = 0.008), while patients without depression or with mild depression kept a stable global cognitive function. In the meantime, patients without depression showed significant improvements in immediate memory, visuospatial skill, and language ability. However, no significant improvement in these parameters was shown in depression groups. In multivariable linear regression analysis, depression at baseline was a significant predictor of worsening global cognitive function, whether depression was analyzed as a continuous variable (odds ratio [OR] = -0.14, 95% confidence interval [CI] -0.27, -0.01, p = 0.031) or a rank variable (OR = -1.88, 95% CI -3.30, -0.45, p = 0.010). Moreover, higher depression score or more severe depression degradation was significantly associated with decline of immediate memory, delayed memory, and language skill.Conclusion:Depression was a significant risk factor for worsening of CI in PD patients.

Effect of the interleukin 10 polymorphisms on interleukin 10 production and visceral hypersensitivity in Chinese patients with diarrhea-predominant irritable bowel syndrome.

BACKGROUND: Irritable bowel syndrome (IBS), a functional gastrointestinal disorder, is characterized by cytokine imbalance. Previously, decreased plasma interleukin 10 (IL-10) level was reported in patients with IBS, which may be due to genetic polymorphisms. However, there are no reports correlating the IL-10 polymorphisms with IL-10 production in patients with IBS. This study aimed to analyze the effect of IL-10 polymorphisms on IL-10 production and its correlation with the clinical symptoms in Chinese patients with diarrhea-predominant IBS (IBS-D). METHODS: Two IL-10 single nucleotide polymorphisms (rs1800871 and rs1800896) were detected in 120 patients with IBS-D and 144 healthy controls (HC) using SNaPshot. IBS symptom severity score, Bristol scale, hospital anxiety, and depressive scale (HADS) were used to evaluate the clinical symptoms, as well as the psychological status and visceral sensitivity of the subjects. IL-10 levels in the plasma and peripheral blood mononuclear cell (PBMC) culture supernatant were measured using enzyme-linked immunosorbent assay, while those in ileal and colonic mucosal biopsies were measured using immunohistochemistry. RESULTS: The frequency of rs1800896 C allele was significantly lower in the patients with IBS-D than that in the HC (odds ratio: 0.49, 95% confidence interval: 0.27-0.92, P = 0.0240). The IL-10 levels in the plasma (P = 0.0030) and PBMC culture supernatant (P = 0.0500) of the CT genotype subjects were significantly higher than those in the TT genotype subjects. The CT genotype subjects exhibited a higher pain threshold in the rectal distention test than the TT genotype subjects. Moreover, IL-10 rs1800871 GG genotype subjects showed an increase in the HADS score compared to other genotype subjects. CONCLUSIONS: IL-10 rs1800896 C allele is correlated with higher IL-10 levels in the plasma and the PBMC culture supernatant, which is associated with a higher pain threshold in the Chinese patients with IBS-D. This study provides an explicit relationship of IL-10 polymorphisms with IL-10 production, which might help in understanding the pathogenesis of IBS-D.

A population-based survey of gastroesophageal reflux disease in a region with high prevalence of esophageal cancer in China.

BACKGROUND: The exact relationship between gastroesophageal reflux disease (GERD) and esophageal squamous cell cancer (ESCC) is far from clarification. The aim of this study was to investigate the epidemiology of GERD in a region with high prevalence of ESCC in China. METHODS: A population-based, cross-sectional study was conducted in a high ESCC prevalent area, Anyang, Henan, China. All subjects fulfilled questionnaires and underwent gastroendoscopy with routine esophageal biopsy. The subjects were divided into GERD subtypes (reflux esophagitis [RE] and non-erosive reflux disease [NERD]) and controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to examine risk factors for RE and NERD. RESULTS: A total of 2844 subjects were finally enrolled. The prevalence of GERD (RE + NERD) was 17.3%. Among them, 271 (9.53%) adults were diagnosed with RE. The prevalence of RE increased with age (7.09% in 45-50 years, 8.00% in 51-60 years, and 9.53% in 61-69 years, χ = 62.216, P < 0.001). Sixty-seven (2.36%) subjects were diagnosed with the silent RE. A total of 221 (7.77%) subjects were diagnosed with NERD. Frequent liquid food consumption (OR [95% CI]: 1.502 [1.076-2.095]) was independent risk factor for RE as well as age, male gender, high body mass index (BMI), ever smoking. Age was independent risk factor for NERD. For silent RE, age, male gender, and frequent liquid food consumption were risk factors. CONCLUSIONS: In the population with high prevalence of ESCC, a high prevalence of GERD and inverted proportion of RE/NERD were presented. Age was an independent risk factor for GERD. The male gender, high BMI, smoking, and frequent liquid food consumption may be risk factors for RE but not for NERD.

Characteristic dysbiosis of gut microbiota of Chinese patients with diarrhea-predominant irritable bowel syndrome by an insight into the pan-microbiome.

BACKGROUND: Irritable bowel syndrome (IBS) is reported associated with the alteration of gut microbial composition termed as dysbiosis. However, the pathogenic mechanism of IBS remains unclear, while the studies of Chinese individuals are scarce. This study aimed to understand the concept of dysbiosis among patients with Chinese diarrhea-predominant IBS (IBS-D), as a degree of variance between the gut microbiomes of IBS-D population and that of a healthy population. METHODS: The patients with IBS-D were recruited (assessed according to the Rome III criteria, by IBS symptom severity score) from the Outpatient Department of Gastroenterology of Peking University Third Hospital, and volunteers as healthy controls (HCs) were enrolled, during 2013. The 16S rRNA sequences were extracted from fecal samples. Ribosomal database project resources, basic local alignment search tool, and SparCC software were used to obtain the phylotype composition of samples and the internal interactions of the microbial community. Herein, the non-parametric test, Wilcoxon rank-sum test was carried out to find the statistical significance between HC and IBS-D groups. All the P values were adjusted to q values to decrease the error rate. RESULTS: The study characterized the gut microbiomes of Chinese patients with IBS-D, and demonstrated that the dysbiosis could be characterized as directed alteration of the microbiome composition leading to greater disparity between relative abundance of two phyla, Bacteroidetes (Z = 4.77, q = 1.59 × 10) and Firmicutes (Z = -3.87, q = 5.83 × 10). Moreover, it indicated that the IBS symptom features were associated with the dysbiosis of whole gut microbiome, instead of one or several certain genera even they were dominating. Two genera, Bacteroides and Lachnospiracea incertae sedis, were identified as the core genera, meanwhile, the non-core genera contribute to a larger pan-microbiome of the gut microbiome. Furthermore, the dysbiosis in patients with IBS-D was associated with a reduction of network complexity of the interacted microbial community (HC vs. IBS-D: 639 vs. 154). The disordered metabolic functions of patients with IBS-D were identified as the potential influence of gut microbiome on the host (significant difference with q < 0.01 between HC and IBS-D). CONCLUSIONS: This study supported the view of the potential influence of gut microbiome on the symptom of Chinese patients with IBS-D, and further characterized dysbiosis in Chinese patients with IBS-D, thus provided more pathological evidences for IBS-D with the further understanding of dysbiosis.

The Association of Cognitive Impairment with Peritoneal Dialysis-Related Peritonitis.

Background:Research on the association between cognitive impairment (CI) and peritoneal dialysis (PD)-related peritonitis is limited. Therefore, we investigated whether CI contributed to the risk of PD-related peritonitis.Methods:This prospective cohort study enrolled 458 patients from 5 PD centers between 1 March 2013, and 30 November 2013, and continued until 31 May 2016. We used the Modified Mini-Mental State Examination (3MS) to assess general cognition, the Trail-Making Test to assess executive function, and subtests of the Battery for the Assessment of Neuropsychological Status to assess immediate and delayed memory, visuospatial skills, and language ability. Patients were assigned to CI and non-CI groups based on their 3MS scores. The first episode of peritonitis was the primary endpoint event. Treatment failure of peritonitis was defined as peritonitis-associated death or transfer to hemodialysis. We used competing risk models to analyze the association between CI and the risk of peritonitis. The association of CI with treatment failure after peritonitis was analyzed using logistic regression models.Results:Ninety-four first episodes of peritonitis were recorded during a median follow-up of 31.4 months, 18.1% of which led to treatment failure. No significant group differences were observed for the occurrence, distribution of pathogenic bacteria, or outcomes of first-episode peritonitis. Immediate memory dysfunction was independently associated with a higher risk of PD-related peritonitis (hazard ratio [HR] 1.736, 95% confidence interval [CI] 1.064 - 2.834, p < 0.05), adjusting for confounders.Conclusions:Immediate memory dysfunction was a significant, independent predictor of PD-related peritonitis. Neither general nor specific domains of CI predicted treatment failure of peritonitis.

Cognitive Changes in Peritoneal Dialysis Patients: A Multicenter Prospective Cohort Study.

RATIONALE & OBJECTIVE: Cognitive impairment is an independent predictor of technique failure and mortality in patients on peritoneal dialysis (PD) therapy. We investigated changes in cognitive function and factors associated with it in this population. STUDY DESIGN: Multicenter prospective cohort study. SETTING & PARTICIPANTS: 458 PD patients were enrolled and followed up for 2 years. PREDICTORS: Global and specific domains of cognitive function were measured at baseline and after 2 years. The Modified Mini-Mental State Examination (3MS) was used for assessment of global cognitive function; Trail-Making Tests A and B, for executive function; and subtests of the Battery for the Assessment of Neuropsychological Status, for immediate and delayed memory, visuospatial skill, and language ability. OUTCOMES: The primary outcome was change in cognitive function. Secondary outcomes included all-cause mortality, cardiovascular mortality, hospitalization, and transition to hemodialysis therapy. ANALYTICAL APPROACH: Multivariable linear regression models. RESULTS: The prevalence of cognitive impairment increased from 19.8% to 23.9%. 3MS scores significantly decreased (84.8 to 83.1), although executive function, immediate memory, and visuospatial skill improved over time. Delayed memory capacity and language ability were unchanged. Lower serum albumin level was associated with deteriorated delayed memory, visuospatial skill, and language ability, as well as with the decline in general cognitive function (ß values of 0.64, 0.90, 0.80, and 0.44, respectively). Advanced age, lower education, and depression were also correlated with deterioration in general and specific cognitive function. After multivariable adjustment, both global and specific cognitive impairment at baseline were associated with a greater rate of hospitalization, and memory dysfunction was associated with a lower dialysis modality survival rate. LIMITATIONS: A relatively short observation period, small number of deaths, and potential selection bias due to patients unavailable for the second assessment. CONCLUSIONS: In a PD population, global cognitive function declined over 2 years, though some specific cognitive domains improved. Besides well-recognized factors, hypoalbuminemia and depression were also risk factors for cognitive impairment.

Early life esophageal acid exposure reduces expression of NMDAR1 in the adult rat dorsal hippocampus and medial prefrontal cortex: Potential relationship with hyperlocomotion.

OBJECTIVE: Early life esophageal acid exposure causes long-term molecular alterations in the rostral cingulate cortex; however, whether it induces behavioral changes remains unverified. Little is known about the molecular changes resulting from this event in the developing hippocampus and medial prefrontal cortex (mPFC). This study aimed to investigate the influence of early life esophageal acid exposure on spontaneous locomotor behavior and N-methyl-D-aspartate receptor (NMDAR), expression in these brain regions of adult rats. METHODS: Male Sprague-Dawley rats were administered with an esophageal acid or saline infusion once per day (postnatal days 7-14). Some of these rats were given acute esophageal acid rechallenge in adulthood (postnatal day 60). The spontaneous locomotor behavior and expressions of esophageal epithelial caludin-1 and NMDAR subunits in the dorsal hippocampus (DH), ventral hippocampus (VH) and mPFC of the adult rats were recorded. RESULTS: Neonatal esophageal acid stimulation caused long-term impairment of the tight junctions in the adult esophagus. Simultaneously, hyperlocomotion and reduced expression of NMDAR1 subunits in both the DH and mPFC were observed, but not in the VH regions. Adult acute acid rechallenge reversed the decreased NMDAR1 expression in the DH and mPFC. The glycine ligand to NMDAR1 subunits was also changed. CONCLUSIONS: Peripheral visceral stimulation such as esophageal acid exposure during cerebral development induces increased locomotor activity, which may be related to the alteration of central sensitivity via NMDAR1 subunit reduction in the DH and mPFC. The impairment of tight junctions in the esophageal epithelium may contribute to the formation of central neuroplasticity.

An association of cognitive impairment with diabetes and retinopathy in end stage renal disease patients under peritoneal dialysis.

BACKGROUND: Diabetes and retinopathy have been considered as risk factors of cognitive impairment (CI) in previous studies. We investigated both of these two factors and their relationship with global and specific cognitive functions in end stage renal disease patients under peritoneal dialysis (PD). METHODS: In this multicenter cross-sectional study, 424 clinically stable patients were enrolled from 5 PD units, who performed PD for at least three months and completed fundoscopy examination if they had diabetes. Global cognitive function was measured using the Modified Mini-Mental State Examination (3MS), Trail-Making Test forms A and B for executive function, and subtests of the Battery for the Assessment of Neuropsychological Status for immediate and delayed memory, visuospatial skills, and language ability. RESULTS: PD Patients with DM and Retinopathy had significantly higher prevalence of CI, executive dysfunction, impaired immediate memory and visuospatial skill, compared with patients in non-DM group. By multivariate logistic regression analyses, DM and retinopathy rather than DM only were significantly associated with increased risk for CI, executive dysfunction, impaired immediate memory and visuospatial skill, odds ratios(ORs) and 95% confidence intervals were 2.09[1.11,3.92], 2.89[1.55,5.37], 2.16 [1.15,4.06] and 2.37[1.32,4.22], respectively (all P < 0.05). CONCLUSIONS: Diabetic PD patients with retinopathy were at two times risk for overall cognitive impairment, executive dysfunction, impaired immediate memory and visuospatial skill as compared to non-diabetic PD patients.

Performance of the Modified Mini-Mental State Examination (3MS) in Assessing Specific Cognitive Function in Patients Undergoing Peritoneal Dialysis.

PURPOSE: While Cognitive impairment (CI) has been identified as an independent risk factors for mortality in patients undergoing peritoneal dialysis (PD), it is inadequately assessed. We evaluated the applicability of the Modified Mini-Mental State Examination (3MS) in assessing specific cognitive function and compared it to a detailed neuropsychological test battery as the reference standard. METHODS: In this multicentric cross-sectional study, we enrolled 445 clinically stable patients from five PD units, who were undergoing PD for at least 3 months. The 3MS was evaluated for general cognitive function. A detailed neuropsychological battery including domains of immediate memory, delayed memory, executive function, language, and visuospatial ability were evaluated as reference standards. Sensitivity and specificity of the 3MS was determined by using receiver operating characteristic (ROC) analysis. RESULTS: The CI prevalence evaluated by 3MS was 23.6%. PD patients with CI performed worse in all cognitive domains. The 3MS correlated well with specific cognitive domains. However, 18.5%, 57.4%, 12.6%, 8.8%, and 41.2% of patients whom were idendified as normal by 3MS still showed executive dysfunction, immediate memory impairment, delayed memory impairment, and language-ability and visuospatial-ability impairment, respectively. The 3MS identified patients having specific cognitive dysfunction with varied extent of diagnostic value, with 0.50, 0.42, 0.35, 0.34, and 0.26 of Youden index in executive function, delayed memory, language ability, immediate memory, and visuospatial ability, respectively. CONCLUSIONS: The 3MS is not a comprehensive instrument for major cognitive domains in PD patients. It could, however, be used for executive dysfunction and delayed memory impairment screening.