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Background: To evaluate associations between diabetes mellitus (DM) coexisting with hyperlipidemia and mortality in peritoneal dialysis (PD) patients. Methods: This was a retrospective cohort study with 2939 incident PD patients in China from January 2005 to December 2018. Associations between the DM coexisting with hyperlipidemia and mortality were evaluated using the Cox regression. Results: Of 2939 patients, with a median age of 50.0 years, 519 (17.7%) died during the median of 35.1 months. DM coexisting with hyperlipidemia, DM, and hyperlipidemia were associated with 1.93 (95% CI 1.45 to 2.56), 1.86 (95% CI 1.49 to 2.32), and 0.90 (95% CI 0.66 to 1.24)-time higher risk of all-cause mortality, compared with without DM and hyperlipidemia, respectively (P for trend < 0.001). Subgroup analyses showed a similar pattern. Among DM patients, hyperlipidemia was as a high risk of mortality as non-hyperlipidemia (hazard ratio 1.02, 95%CI 0.73 to 1.43) during the overall follow-up period, but from 48-month follow-up onwards, hyperlipidemia patients had 3.60 (95%CI 1.62 to 8.01)-fold higher risk of all-cause mortality than those non-hyperlipidemia (P interaction = 1.000). Conclusions: PD patients with DM coexisting with hyperlipidemia were at the highest risk of all-cause mortality, followed by DM patients and hyperlipidemia patients, and hyperlipidemia may have an adverse effect on long-term survival in DM patients. [ABSTRACT FROM AUTHOR]

Objectives. The monocyte-to-lymphocyte ratio (MLR), as a new marker of the systemic inflammatory response, is associated with cardiovascular disease (CVD) mortality in the general population and hemodialysis patients. However, the association between the MLR and CVD mortality in peritoneal dialysis (PD) has received little attention. Methods. In this multicenter retrospective cohort study, 1753 incident PD patients from November 1, 2005, to June 30, 2017, with a baseline MLR were enrolled. The primary endpoint was CVD mortality. The association of MLR with CVD mortality was assessed using a multivariable-adjusted Cox model and the Fine and Gray competing risk model. Results. Of 1753 patients, the mean age was 51.1 ± 14.9 years, 56.9% of patients were male, and the Charlson comorbidity index was 4.29 ± 1.75. During the follow-up period of 31.2 ± 18.4 months, 368 patients died, of which 200 (54.3%) deaths were caused by CVD events. CVD mortality rates for the lowest, middle, and highest MLR tertiles were 70.6, 78.4, and 88.9 per 1000 patient-years, respectively (P < 0.001). Kaplan-Meier analysis revealed that survival rates were significantly different among the three MLR groups (log rank = 22.41 , P < 0.001). After adjusting for confounding factors, the highest MLR tertile was significantly associated with a hazard ratio (HR) for CVD mortality of 1.45 (95% confidence interval, 1.13-2.51, P = 0.016). The Fine and Gray method analysis showed that using all-cause mortality as competing risk, the highest MLR tertile remained an independent predictor of CVD mortality (HR = 1.39 , 95% CI 1.10-2.47, P = 0.021). Conclusions. Higher MLR levels at the commencement of PD may be independently associated with increased CVD mortality in PD patients. [ABSTRACT FROM AUTHOR]

Gallic acid (GA) is a natural polyphenolic compound derived from Rhus chinensis Mill. with a variety of biological activities such as astringent sweat, cough, dysentery, hemostasis, and detoxification, and is widely used in China as a treatment for cough, bleeding, and gastrointestinal disorders. In recent years, the anticancer activity of GA has been demonstrated in a variety of cancers, affecting multiple cellular pathways associated with cancer onset, development and progression. To investigate the role and potential mechanism of GA on gastric precancerous lesions (GPL), the key turning point of gastritis to gastric cancer, with the aim of delaying, blocking or reversing the dynamic overall process of "inflammation-cancer transformation" and thus blocking GPL to prevent the development of gastric cancer. In this study, we established N-Nitroso-N-methylurea (MNU)-induced GPL mice model and induced precancerous lesions of gastric cancer cells (MC), i.e. epithelial mesenchymal transition (EMT), in human gastric mucosal epithelial cells (GES-1) with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG). We used conventional pathology, immunohistochemistry, RNA sequencing, Western blot and other techniques to study the therapeutic effect of GA on GPL and its possiblemechanism in vitro and in vivo. The results showed that compared with normal GES-1 cells, MC cells had the characteristics of malignant cells such as abnormal proliferation, invasion and metastasis, accompanied by decreased expression of EMT-related protein E-cadherin and increased expression of N-cadherin and Vimentin. GA can inhibit the malignant behavior of MC cell proliferation and induce its G0/G1 phase arrest, which is achieved by downregulating the Wnt/β-catenin signaling pathway and thereby inhibiting the EMT process. However, when we incubated with the Wnt pathway activator (Wnt agonist 1), the effect of GA was reversed. Furthermore, analysis of human gastric specimens showed that activation of the Wnt/β-catenin pathway was significantly associated with GPL pathological changes. Meanwhile, GA reversed MNU-induced intestinal metaplasia and partial dysplasia in GPL mice. Taken together, these results indicate that GA prevents the occurrence and development of GPL by inhibiting the Wnt/β-catenin signaling pathway and then inhibiting the EMT process, which may become potential candidates for the treatment of GPL. [Display omitted] [ABSTRACT FROM AUTHOR]

Left ventricular (LV) diastolic function was found to be a significant predictor of cardiovascular events and general mortality in dialysis. Studies have indicated that dialysate calcium concentrations were significantly associated with cardiac function. However, the relationship between low calcium dialysate and LV diastolic function has not been clear. The aim of this study was to investigate the influence of low calcium dialysate on cardiac function in peritoneal dialysis (PD) patients. A total of 60 PD patients were enrolled in this study, with a calcium content of the PD solution of 1.25 mmol/L in 30 patients (low-calcium group) and 1.75 mmol/L in 30 patients (standard-calcium group). Standard M-mode and two-dimensional ultrasound measurements were applied to detect the cardiac function. After 12-month follow-up, we found no significant difference in blood pressure, calcium, phosphorus, parathyroid hormone (PTH), etc., between the two groups. Residual renal function (RRF), which is associated with LV cardiac function, was significantly decreased in the standard-calcium group compared with the low-calcium group (5.64 ± 3.23 vs. 9.38 ± 3.17,p = .001). Compared with the low-calcium group,Emax(peak early diastolic velocity) andAmax(peak late diastolic velocity) were significantly decreased (p < .05), whereas myocardial performance index (MPI) was obviously increased in standard-calcium group (9.69 ± 2.71 vs. 7.75 ± 0.93,p < .05). In conclusion, our data suggest that low calcium dialysate treatment is significantly associated with better LV diastolic function. [ABSTRACT FROM AUTHOR]

Podocyte injury is a vital factor, which induces massive proteinuria. Studies have shown that tacrolimus (TAC) protected podocyte via stabilizing cytoskeleton. Our latest study indicates that calcineurin binding protein 1 (Cabin1) undergoes nuclear translocation during podocytes injury. Whether TAC targets on Cabin1 during podocyte injury is still not clear. This study establishes non-immunological proteinuric model. To observe the effect of the treatment of TAC on Cabin1 expression in 5/6 nephrectomized rats. Sprague–Dawley rats were injected with TAC (0.2 mg/kg/day) for 4–8 weeks after 5/6 nephrectomy. Then, rats were sacrificed in the eighth week after operation, renal tissues were processed for morphological studies under light and electrical microscope. Cabin1 expression and distribution were detected by western blot and indirect immunofluorescence staining. In 5/6 nephrectomized rats, urinary protein excretion reached 90.2 ± 30.1 mg/24 h, glomerular sclerosis index and tubulointerstitial fibrosis score were significantly increased, and widespread of podocyte foot processes fusion was found. Moreover, Cabin1 protein expression was markedly increased, and its distribution became much more obviously in podocytes nuclei. In TAC treated rats, urinary protein excretion significantly decreased (44.9 ± 22.5 mg/24 h), glomerular sclerosis and tubulointerstitial fibrosis were alleviated, and podocyte foot processes fusion was inhibited. Furthermore, TAC alleviated the increased protein expression and abnormal distribution of Cabin1. In conclusion, TAC restores podocyte injury and stabilizes the expression of Cabin1. Cabin1 may become a new target to demonstrate the mechanism of TAC in podocyte injury. [ABSTRACT FROM AUTHOR]

Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric illnesses with heritability of up to 38%. The fat mass- and obesity-associated (FTO) gene, in particular the single nucleotide polymorphism (SNP) rs9939609, has been identified as a genetic risk loci associated with MDD. However, most prior studies have involved European and American populations. Whether rs9939609 is an true risk SNP for MDD in Asian populations remains inconclusive. Methods: In the present study, we conducted a meta-analysis of the association between rs9939609 and MDD in Asian populations by combining 5 available case-control samples totaling 6531 cases and 12,359 controls. Results: Our meta-analysis suggests that rs9939609 is not a risk SNP for MDD in Asian populations by fixed effect model (Z=1.04, P=0.30, OR=0.96, 95% CI=0.90-1.03). Limitations: The age distribution and gender ratios were not matched well in the combined samples of cases and controls. Publication bias might be also considered with only a relatively small number of association studies of FTO rs9939609 with MDD in Asian populations. Conclusions: The absence of association of rs9939609 with MDD in our Asian populations suggests a potential genetic heterogeneity in the susceptibility of MDD on this locus. [ABSTRACT FROM AUTHOR]

Context: Podocyte injury is related to increasing proteinuria and contributes to the progression of kidney disease. Calcineurin binding protein 1 (Cabin1) is a repressor of myocyte enhancer factor 2 (MEF2) and calcineurin-mediated transcription in the immune system. Moreover, Cabin1 interacts with p53 and negatively regulates p53 in tumor cells. However, its function in kidney is unknown.Objective: To explore the exact localization of Cabin1 in glomeruli, as well as the relationship between Cabin1 and podocyte injury.Methods: Sprague–Dawley rats were sacrificed to observe the localization and protein expression of Cabin1 in the kidney. Cabin1 localization and protein expression were detected by immunofluorescence staining and western blot, respectively. Mouse podocytes were cultivated at 33 °C to propagate, then cells were transferred to an incubator at 37 °C to allow differentiation. Differentiated podocytes were stimulated by angiotensin II (AngII) or AngII plus tacrolimus. Cells were harvested to detect the localization and protein expression of Cabin1. Cytoplasmic and nuclear protein were separated by protein extraction kit.Results: Cabin1 mainly localized in the nuclei of glomerular innate cells, it colocalized with WT-1 in podocytes nuclei. Western bolt showed Cabin1 protein remarkably expressed in renal cortex. AngII-induced Cabin1 nuclear protein significantly increased, accompanied by cytoskeleton disruption in cultured mouse podocytes.Conclusion: Cabin1 localizes in glomerular podocytes. AngII induces nuclear translocation of Cabin1 in cultured podocytes. [ABSTRACT FROM AUTHOR]

Poria polysaccharide chemical components can combat tumor and cancer and boost the immune system. It also has antibacterial, antiviral, and anti-inflammatory effect. It has the function of anti-oxidation, and it can delay the age. It is able to protect liver, remove jaundice and promote sound sleep. It can also prevent and remove calculus. It is of the function of dropping glucose and anticoagulating. This paper reviews and analyses the reports and research of functions of Poria polysaccharide and provides references for its clinical application and research. [ABSTRACT FROM AUTHOR]

Purpose: Recent research has shown that hypomagnesemia is associated with increased all-cause mortality in hemodialysis patients. However, the relationship between the long-term prognosis of peritoneal dialysis (PD) and the study is not yet clear. This study will analyze the effects of hypomagnesemia on all-cause, cardiovascular diseases (CVD), and non-CVD mortality in PD patients. Method: In a retrospective cohort study, 1,004 samples were selected from 7 PD centers in China. Based on the baseline blood magnesium level at the beginning of stable dialysis, all patients were classified into blood magnesium <0.7 mmol/L group, 0.7–1.2 mmol/L group, and >1.2 mmol/L group (the end event was death). The Kaplan-Meier method was used to calculate the difference in cumulative survival rate; the Cox proportional hazard model was used to analyze the risk factors of all-cause, CVD, and non-CVD death causes. Results: Cox multiple regression analysis results (reference comparison of 0.7–1.2 mmol/L group): patients with serum magnesium <0.7 mmol/L have a higher risk ratio of all-cause mortality (HR = 1.580, 95% CI: 1.222–2.042, p = 0.001), and it is also obvious after correction by multiple models (HR = 1.578, 95% CI: 1.196–2.083, p = 0.001). Subgroup analysis of the causes of death was as follows: CVD risk (HR = 1.628, 95% CI: 1.114–2.379, p = 0.012) and non-CVD risk (HR = 1.521, 95% CI: 1.011–2.288, p = 0.044). Further analysis of the causes of infection-related death in non-CVD is also significant (HR = 1.919, 95% CI: 1.131–3.1257, p = 0.016). On the other hand, the serum magnesium>1.2 mmol/L group had lower all-cause mortality after correction (HR = 0.687, 95% CI: 0.480–0.985, p = 0.041), and subgroup analysis of the cause of death had no statistical significance (p > 0.05). Conclusions: Hypomagnesemia (serum magnesium <0.7 mmol/L) during stable dialysis in PD patients is a risk factor for CVD- and non-CVD-related mortality, especially infection-related death causes. [ABSTRACT FROM AUTHOR]

The glucose-to-lymphocyte ratio (GLR), a glucose metabolism and systemic inflammatory response parameter, is associated with an adverse prognosis for various diseases. However, the association between serum GLR and prognosis in patients undergoing peritoneal dialysis (PD) is poorly understood. In this multi-center cohort study, 3236 PD patients were consecutively enrolled between 1 January 2009 and 31 December 2018. Patients were divided into four groups according to the quartiles of baseline GLR levels (Q1: GLR ≤ 2.91, Q2:2.91 < GLR ≤ 3.91, Q3:3.91 < GLR < 5.59 and Q4: GLR ≥ 5.59). The primary endpoint was all-cause and cardiovascular disease (CVD) related mortality. The correlation between GLR and mortality was examined using Kaplan–Meier and multivariable Cox proportional analyses. During the follow-up period of 45.93 ± 29.01 months, 25.53% (826/3236) patients died, of whom 31% (254/826) were in Q4 (GLR ≥ 5.59). Multivariable analysis revealed that GLR was significantly associated with all-cause mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p =.019) and CVD mortality (adjusted HR 1.02; CI 1.00 ∼ 1.04, p =.04). Compared with the Q1 (GLR ≤ 2.91), placement in Q4 was associated with an increased risk of all-cause mortality (adjusted HR: 1.26, 95% CI: 1.02 ∼ 1.56, p =.03) and CVD mortality (adjusted HR 1.76; CI 1.31 ∼ 2.38, p <.001). A nonlinear relationship was found between GLR and all-cause or CVD mortality in patients undergoing PD (p =.032). A higher serum GLR level is an independent prognostic factor for all-cause and CVD mortality in patients undergoing PD, suggesting that more attention should be paid to GLR. [ABSTRACT FROM AUTHOR]

Immune-inflammatory biomarkers (IIBs) have been shown to be correlated with prognosis in patients undergoing peritoneal dialysis (PD). In this study, we aimed to evaluate the relationship between a novel comprehensive biomarker, the pan-immune-inflammation value (PIV), and the prognosis of patients undergoing PD. We retrospectively analyzed data from a multicenter, large-sample PD database. PIV was calculated as (neutrophil count × platelet count × monocyte count)/lymphocyte count. The prognostic endpoints in this study were all-cause death all-cause, cardiovascular disease (CVD) and infection-related death. The Kaplan–Meier method, a Cox proportional hazards regression, Fine–Gray competing risk model, smooth curve, and subgroup analysis were used to analyze the independent relationship between PIV and the prognosis of patients undergoing PD. A total of 2796 cases of PD were included, and the study population was divided into Tertiles 1, 2, and 3, according to the tertiles of baseline PIVs. After adjusting for multiple model factors, patients in the Tertile 3 group had a significantly higher risk of all-cause death, CVD death and infection-related death compared with patients with PIV in the Tertile 1 group. Interaction tests showed no positive correlations for subgroup parameters. Regarding all-cause death, compared with the lowest tertile, the multivariable-adjusted hazard ratios (95% confidence intervals) of the highest and middle tertiles were 1.55 (1.25–1.94) and 1.77 (1.43–2.19), respectively; PIV (log2 processing) was associated with 17% excess of mortality in the continuous model. A high PIV at baseline was significantly associated with an increased risk of deaths due to all-causes, CVD and infection in patients undergoing PD. [ABSTRACT FROM AUTHOR]

Background: Primary dysmenorrhea (PD), is one of main gynecological complaints in women of child-bearing age. Common medications for PD do not always achieve satisfactory outcome of pain relief. Hence, both health professionals and patients are seeking help from complementary and alternative medicine. The acupoint herbal plaster (AHP), which appears to be a safe and effective way to alleviate menstrual pain, as well as to improve other PD-related symptoms. Despite similar clinical studies for this condition in the past, no high-quality methodology-based clinical trial has been reported to date. The current study aims to assess the efficacy of the AHP compared with the acupoint placebo plaster (APP) and being placed on a waiting-list control group in patients with primary dysmenorrhea.Methods/design: This study is a randomized, single-center, placebo-controlled clinical trial. A total of 180 women with PD will be included and randomly allocated to the AHP, APP and waiting-list (WL) groups in a 1:1:1 ratio. Patients in the AHP group will be provided with herbal plasters (Shaofuzhuyu decoction) on various acupoints: Shenque (CV8), Guanyuan (CV4), Qihai (CV5), Ciliao (BL32) and Zigong (EX-CA1). Women in the APP group will receive placebo plasters on the same acupoints, and no intervention will be given to the WL group until completion of the study. The primary outcome will be pain intensity reduction measured by a Visual Analog Scale (VAS), with other outcome measurements including the Cox Menstrual Symptom Scale (CMSS), the 12-Item Short Form Health Survey (SF-12) and the Participant Global Impression of Change (PGIC). All assessments will be performed at baseline, each menstrual cycle during the treatment course and the follow-up course. Any adverse events will be recorded throughout the study.Discussion: This is the first study to compare the changes in menstrual pain after three different interventions: the active intervention (AHP), the placebo intervention (APP), and a period of no intervention (WL). This three-arm randomized controlled trial (RCT) aims to investigate the relative contributions of the specific (AHP vs. APP) and non-specific (APP vs. WL) effects to the overall clinical effects of the active AHP on women with PDM. The scientific and rigorous methodology design of this trial should gather good evidence to assess the curative effects and safety of the AHP on PD. Moreover, the results of this study may provide evidence-based references for the treatment of menstrual pain in future.Trial Registration: Chinese Clinical Trial Registry, ID: ChiCTR-TRC-16008701. Registered on 22 July 2016. [ABSTRACT FROM AUTHOR]

The gut–brain axis is an active area of research. Several representative diseases, including central nervous system disorders (Alzheimer's disease, Parkinson's disease, and depression), metabolic disorders (obesity-related diseases), and intestinal disorders (inflammatory bowel disease and dysbiosis), are associated with the dysfunctional gut–brain axis. Baicalin, a bioactive flavonoid extracted from Scutellaria baicalensis, is reported to exert various pharmacological effects. This narrative review summarizes the molecular mechanisms and potential targets of baicalin in disorders of the gut–brain axis. Baicalin protects the central nervous system through anti-neuroinflammatory and anti-neuronal apoptotic effects, suppresses obesity through anti-inflammatory and antioxidant effects, and alleviates intestinal disorders through regulatory effects on intestinal microorganisms and short-chain fatty acid production. The bioactivities of baicalin are mediated through the gut–brain axis. This review comprehensively summarizes the regulatory role of baicalin in gut–brain axis disorders, laying a foundation for future research, although further confirmatory basic research is required. [ABSTRACT FROM AUTHOR]

Malnutrition and inflammation are associated with mortality in peritoneal dialysis (PD) patients. Serum albumin and non-high-density lipoprotein cholesterol (non-HDL-C) are independently associated with mortality in PD patients. Combining albumin and non-HDL-C with mortality may be more plausible in clinical practice. This retrospective cohort study included 1954 Chinese PD patients from 1 January 2009 to 31 December 2016. Kaplan–Meier curve was used to determine the relationship between albumin to non-HDL-C ratio and all-cause mortality. Cox regression analysis was applied to assess the independent predictive value while adjusting for confounding factors. Competitive risk analysis was used to examine the effects of other outcomes on all-cause mortality prognosis. In the 33-month follow-up period, there were 538 all-cause deaths. Kaplan–Meier analysis presented significant differences in all-cause mortality. Multivariate Cox regression showed that the risk of all-cause mortality was lower in the moderate group (9.36–12.79) (HR, 0.731; 95% CI, 0.593–0.902, p = 0.004) and the highest group (>12.79) (HR, 0.705; 95% CI, 0.565–0.879, p = 0.002) compared to the lowest group (≤9.36). Competitive risk analysis revealed significant differences for all-cause mortality (p < 0.001), while there was no statistical significance for other competing events. Low albumin to non-HDL-C ratio was associated with a high risk of all-cause mortality in PD patients. It may serve as a potential prognostic biomarker in PD patients. [ABSTRACT FROM AUTHOR]

The global mortality rate from chronic kidney disease (CKD) has increased over the past two decades. Typically, peritoneal dialysis (PD) remains a useful alternative treatment for end-stage renal disease. Cardiovascular disease (CVD) is the main complication in PD patients. In terms of prognosis, it is reported that platelet distribution width (PDW) can predict adverse CVD events. However, the relationship between PDW and new-onset CVD in PD patients is not clear. This study aimed to explore the relationship between PDW and new-onset CVD in PD patients. This was a retrospective cohort study, from 4 July 2005 to 31 December 2019, and a total of 1557 patients were recruited. PDW was respectively categorized into two groups: PDW ≤13.2 fL and PDW >13.2 fL. The primary outcome was a new-onset CVD event. Cox proportional hazards models were performed to assess the hazard ratio (HR). Receiver-operating characteristic (ROC) curves were applied to evaluate the predictive accuracy of the PDW on CVD events. During follow-up, 114 new-onset CVD events were recorded. Cox proportional hazards models showed a higher risk of CVD events in patients with high PDW (HR = 1.862 95%CI 1.205–2.877, p = 0.005). Kaplan–Meier cumulative incidence curves showed the risk of the first occurrence of CVD events was greater in the high PDW group (p = 0.006). High PDW is associated with new-onset cardiovascular disease events in PD patients. [ABSTRACT FROM AUTHOR]

A large number of studies have shown that proton pump inhibitors (PPIs) are associated with infection events. Therefore, we retrospectively evaluated the association of PPI therapy with the occurrence of first pneumonia and peritoneal dialysis(PD)-related peritonitis events in the maintenance PD patients. We collected PD patients in two large hospitals from January 1, 2012 to December 31, 2016, and divided them into the PPI group and the non-PPI group. Multivariate Cox proportional hazards models were applied to evaluate the cumulative incidence and hazard ratios (HRs). Inverse probability of treatment weight (IPTW) method was used to adjust for covariate imbalance between the two groups and further confirm our findings. Finally, 656 PD patients were included for data analysis, and the results showed that PPI usage was associated with an increased risk of pneumonia [HR 1.71; 95% CI 1.06-2.76; p = 0.027] and peritonitis [HR 1.73; 95% CI 1.24-2.40; p = 0.001]. IPTW-adjusted HRs for the association of PPIs with pneumonia and peritonitis were 1.58 (95% CI:1.18-2.12; p = 0.002) and 2.33 (95% CI:1.91-2.85; p < 0.001), respectively. Moreover, the competitive risk model proved that under the conditions of competition for other events(including transfer to hemodialysis therapy, kidney transplant, transfer from our research center, loss to follow-up, and death), the differences in endpoints events between the two groups were still statistically significant (p = 0.009, p < 0.001, respectively). PPIs was associated with an increased risk of first pneumonia and PD-related peritonitis events in PD patients, which reminds clinicians to be cautious when prescribing acid-suppressing drugs for PD patients. [ABSTRACT FROM AUTHOR]

A long period of inappropriate proton pump inhibitors (PPI) treatment has been proved to be associated with adverse prognosis in general population and hemodialysis patients. This study was conducted to clarify the impact of PPI usage on mortality and adverse cardiovascular (CV) events in peritoneal dialysis (PD) patients. This is a retrospective study. A total of 905 patients were enrolled from two PD centers, including 211 patients on PPI treatment and 618 patients not on PPIs. Kaplan–Meier curves were used to identify the incidence of adverse outcomes. Multivariate Cox regression models and inverse probability of treatment weighting (IPTW) were applied to analyze hazard ratios (HRs) for adverse outcomes. During follow-up, 162 deaths and 102 CV events were recorded. Kaplan–Meier curve demonstrated all-cause mortality (log-rank test p =.018) and CV events (log-rank test p =.024) were significantly higher in PPI usage group. Multivariate Cox regression models and IPTW showed that PPI usage was an indicator for all-cause mortality (HR = 1.35, 95%CI = 1.09–1.67, p =.006) and CV events (HR = 1.78, 95%CI = 1.35–2.32, p <.001). PPI usage is associated with higher all-cause mortality and CV events in PD patients. Clinicians are supposed to be more careful when using PPI and need to master the indications more rigorously in patients receiving PD treatment. [ABSTRACT FROM AUTHOR]

The Huanglian-Hongqu herb pair (HH) is a synergistic drug combination used to treat non-alcoholic fatty liver disease (NAFLD). However, the molecular mechanism underlying the therapeuticeffects of HH requires further elucidation. The present study explored the potential mechanism of HH in treating NAFLD. UPLC-Q-TOF-MS was employed to identify the drug constituents in HH. A NAFLD rat model was induced by a high-fat diet (HFD) and treated with different doses of HH. The functional mechanism of HH in NAFLD rats was predicted using network pharmacology, metabolomics and transcriptomics. Immunohistochemistry, real-time PCR, and Western blot were performed to validate the key mechanisms. Pharmacodynamic assessment demonstrated that HH exhibited improvements in lipid deposition and reduced hepatic oxidative stress in NAFLD rats. Hepatic wide-target metabolomics revealed that HH primarily modulated amino acids and their metabolites, fatty acids, organic acids and their derivatives, bile acids, and other liver metabolites. The enriched pathways included metabolic pathways, primary bile acid biosynthesis, and bile secretion. Network pharmacology analysis indicated that HH regulated the key pathways in NAFLD, notably PPAR, AMPK, NF-κB and other signaling pathways. Furthermore, hepatic transcriptomics, based on Illumina RNA-Seq sequencing analyses, suggested that HH improved NAFLD through metabolic pathways, the PPAR signaling pathway, primary bile acid biosynthesis, and fatty acid metabolism. Further mechanistic studies indicated that HH could regulate the genes and proteins associated with the PPAR signaling pathway. Our findings demonstrated that the potential therapeutic benefits of HH in ameliorating NAFLD by targeting the PPAR signaling pathway, thereby facilitating a more extensive use of HH in NAFLD. [Display omitted] • HH is a Chinese hebal formulasis combination used for glucose and lipid metabolism disorders. • HH can mitigate lipid diposition and reduce hepatic oxidative stress in NAFLD rats. • HH may ameliorate NAFLD by targeting the PPAR signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Low levels of high-density lipoprotein cholesterol (HDL-C) and diabetes are common in patients undergoing peritoneal dialysis (PD). The aim of this study was to investigate the association between the coexistence of diabetes with a low level of HDL-C and the first episode of peritoneal dialysis-related peritonitis (PDRP) in patients with PD. Methods: We retrospectively investigated patients with PD from January 1, 2003, to May 31, 2020, in four PD centers. Patients with PD were divided into four groups: no comorbidities, low HDL-C only, diabetes only, and diabetes plus low HDL-C. The clinical and laboratory baseline data of the four groups were collected and compared. The association between diabetes coexisting with low HDL-C levels and the first episode of PDRP was analyzed by multivariate Cox regression analysis. Results: A total of 1013 patients with PD were included in our study. The mean age was 49.94 ± 14.32 years, and 597 (58.99%) patients were males. A total of 301 (29.7%) patients had their first episodes of PDRP, and low HDL-C levels coexisted with diabetes in 72 patients with PD. After adjusting for confounding factors, a low level of HDL-C coexisting with diabetes was significantly associated with the first episode of PDRP in our study (hazard ratio: 2.81, 95% CI 1.32 ~ 4.73, p = 0.005). The associations among HDL-C, diabetes and PDRP were consistent in the following subgroups: sex, age, and pre-existing CVD (all P interaction > 0.05). Conclusions: Patients with both diabetes and low HDL-C levels were at higher risk for PDRP in patients with PD. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal bleeding (GIB) is widespread in patients with impaired renal function. Whether angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) potentially take a crucial role in avoiding GIB incidence among peritoneal dialysis (PD) patients is unknown. Methods: Overall, 734 PD patients were enrolled after using propensity score matching. Kaplan–Meier analysis and COX regression were used to explore correlation between ACEi/ARBs and GIB. Competitive risk model was aimed to identify whether other events were confounding factors. Forest plot was applied to assess the influence of ACEI/ARBs on GIB incidence in different groups. Results: During 8-year follow-up, 89 (12.13%) cases of GIB were recorded. Kaplan–Meier analysis revealed that the incidence of GIB among patients taking ACEi/ARBs was lower than those subjects who had not (log rank = 6.442, P = 0.011). After adjusted different confounding factors, administration of ACEi/ARBs was associated with lowered GIB incidence (adjusted HR = 0.49, 95% CI 0.32–0.77, P = 0.002). In competitive risk model, considering of other events, the incidence of GIB in two groups was still statistically significant (P = 0.010). Subgroup analysis showed ACEi/ARBs taking impeded GIB in the ≥ 60 age group (HR = 0.52, 95% CI 0.28–0.98, P = 0.040). Conclusion: PD patients who were submitted to ACEi/ARBs inclined to have a lower risk for GIB. In this regard, ACEi/ARBs offered a promising choice to GIB. [ABSTRACT FROM AUTHOR]

Recently, increasing numbers of studies have shown that the consumption of large amounts of alcohol is a major risk factor for dementias, which has led to widespread concern about the harmful effects of alcohol consumption on health. However, the pathological changes in the brain caused by this habit are not clear. This study aimed to investigate the possible causes by determining the permeability of the blood–brain barrier (BBB), pathomorphological changes, the mRNA, and protein expressions of adhesion proteins and the concentrations of β-amyloid (Aβ) and some related functional proteins in the brains of C57BL/6 and APPswe/PS1dE9 mice before and after intragastric administration of alcohol for 2 months. The results showed that long-term consumption of alcohol aggravated cognitive decline, increased the permeability of the BBB, led to pathomorphological changes and downregulated some related structural proteins (zonula occludens-1, VE-cadherin, and occludin) and functional proteins (major facilitator superfamily domain-containing protein-2a (Mfsd2a), low-density lipoprotein receptor-related protein-1 (LRP1), receptor for advanced glycation end products (RAGE), and aquaporin-4 (AQP4)) in the BBB but did not increase the concentration of Aβ1-42. These novel findings suggested that long-term consumption of alcohol induces neural lesions, which is related to the destruction of the integrity of the BBB. [ABSTRACT FROM AUTHOR]

Qinlian Hongqu decoction (QLHQD) is a traditional Chinese medicine (TCM) formula. It has previously been found to mitigate hyperlipidemia, although its mechanism requires further clarification. This study explored QLHQD's mechanism in treating hyperlipidemia based on network pharmacology and experimental validation. The components of QLHQD were analyzed by means of ultrahigh performanceliquid chromatography-quadrupole/orbitrapmass spectrometry (UHPLC-Q-Orbitrap-HRMS) and the targets of hyperlipidemia were predicted using the Swiss ADME, GeneCards, OMIM, DrugBank, TTD, and PharmGKB databases. A drug-component-target-disease network was constructed using Cytoscape v3.7.1. Moreover, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses were performed using the Bioinformatics platform. Based on the KEGG results, the non-alcoholic fatty liver disease signaling pathways were selected for experimental validation in an animal model. We identified 34 components of QLHQD, 94 targets of hyperlipidemia, and 18 lipid metabolism-related pathways from the KEGG analysis. The results of the animal experiment revealed that QLHQD alleviated lipid metabolism disorders, obesity, insulin resistance, and inflammation in rats with hyperlipidemia induced by high-fat diets. Additionally, it reduced the expression of IRE1-α, TRAF2, IKKB-β, and NF-κB proteins in the liver of hyperlipidemic rats. QLHQD is able to significantly mitigate hyperlipidemia induced via high-fat diets in rats. The mechanism of action in this regard might involve regulating the IRE1-α/IKKB-β/NF-κB signaling pathway in the liver, thereby attenuating inflammatory responses and insulin resistance. [Display omitted] • QLHQD mitigates lipid metabolism disorder in a hyperlipidemia rat model. • QLHQD attenuates inflammatory responses and insulin resistance in the liver. • QLHQD mainly ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]

Atherosclerosis, the main cause of cardiovascular disease (CVD), is prevalent in patients undergoing peritoneal dialysis (PD). Atherogenic index (AI) is a strong predictor of atherosclerosis. However, its prognostic value in CVD outcomes and all-cause mortality among patients undergoing PD remains uncertain. Therefore, we aimed to evaluate the association between AI and all-cause and CVD mortality in PD patients. Calculated based on lipid profiles obtained through standard laboratory procedures, AI was evaluated in 2682 patients who underwent PD therapy between January 2006 and December 2017 and were followed up until December 2018. The study population was divided into four groups according to the quartile distribution of AI (Q1: <2.20, Q2: 2.20 to <2.97, Q3: 2.97 to <4.04, and Q4: ≥4.04). Multivariable Cox models were employed to explore the associations between AI and CVD and all-cause mortality was evaluated. During a median follow-up of 35.5 months (interquartile range, 20.9–57.2 months), 800 patients died, including 416 deaths from CVD. Restricted cubic splines showed non-linear relationship between AI and adverse clinical outcomes. The risks of all-cause and CVD mortality gradually increased across quartiles (log-rank, p < 0.001). After adjusting for potential confounders, the highest quartile (Q4) showed significantly elevated hazard ratio (HR) for both all-cause mortality (HR 1.54 [95% confidence interval (CI), 1.21–1.96]) and CVD mortality risk (HR 1.78 [95% CI, 1.26–2.52]), compared to the lowest quartile (Q1). AI was independently associated with all-cause and CVD mortality in patients undergoing PD, suggesting that AI might be a useful prognostic marker. [Display omitted] • The predictive role of atherogenic index (AI) in CVD outcomes in peritoneal dialysis is limited. • We investigated the association between AI and all-cause and CVD mortality. • AI was associated with peritoneal dialysis patient mortality. • AI requires further study as a predictive marker. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a globally prevalent malignancy with a high potential for metastasis. Existing cancer treatments have limitations, including drug resistance and adverse effects. Researchers are striving to develop effective therapies to address these challenges. Impressively, contemporary research has discovered that many natural products derived from foods, plants, insects, and marine invertebrates can suppress the progression, metastasis, and invasion of CRC. In this review, we conducted a comprehensive search of the CNKI, PubMed, Embase, and Web of Science databases from inception to April 2023 to evaluate the efficacy of natural products targeting mitochondria to fight against CRC. Mitochondria are intracellular energy factories involved in cell differentiation, signal transduction, cell cycle regulation, apoptosis, and tumorigenesis. The identified natural products have been classified and summarized based on their mechanisms of action. These findings indicate that natural products can induce apoptosis in colorectal cancer cells by inhibiting the mitochondrial respiratory chain, ROS elevation, disruption of mitochondrial membrane potential, the release of pro-apoptotic factors, modulation of the Bcl-2 protein family to facilitate cytochrome c release, induction of apoptotic vesicle activity by activating the caspase protein family, and selective targeting of mitochondrial division. Furthermore, diverse apoptotic signaling pathways targeting mitochondria, such as the MAPK, p53, STAT3, JNK and AKT pathway, have been triggered by natural products. Natural products such as diosgenin, allopurinol, and clausenidin have demonstrated low toxicity, high efficacy, and multi-targeted properties. Mitochondria-targeting natural products have great potential for overcoming the challenges of CRC therapy. [Display omitted] • The mitochondrial functional state is a potential target for the treatment of carcinoma. • Many natural products can inhibit colorectal cancer by regulating mitochondrial function. • Natural products such as diosgenin, allopurinol, and clausenidin have the clinical potential to treat colorectal cancer. [ABSTRACT FROM AUTHOR]

Background: Although neutrophil-to-lymphocyte ratio (NLR) is closely associated with pneumonia in the general population, its relationship is unclear in peritoneal dialysis (PD) patients. Methods: This is a cohort study consisting of 739 PD patients and dividing into two groups. Kaplan–Meier curves were applied to observe the incidence of the first occurrence of pneumonia, competitive risk analysis was conducted to compare whether there was a significant difference in each NLR group in the presence of other competing events, multivariable COX regression analysis was used to evaluate the hazard ratios (HRs), as well as forest plot was used to analyze the relationship between NLR and the first occurrence of pneumonia in different subgroups. Results: Of all the patients, 116 cases of first-time pneumonia were recorded. The first-time pneumonia incidence rate was 71.67/1000 patient-years in high NLR group, which was markedly higher than that of 45.81/1000 patient-years in low NLR group. Kaplan–Meier curves indicated significant differences in the incidence of the first occurrence of pneumonia between two groups (log-rank test p = 0.015). The competitive risk model suggested a significant difference in the cumulative incidence of first pneumonia between the two groups (p = 0.032). Compared to low NLR group, adjusted Cox model showed that high NLR group was associated with increased risk of pneumonia incidence (HR, 1.51; 95% CI 1.04–2.21; p = 0.031). Forest plot showed no interaction was found in subgroups. Conclusions: The risk of pneumonia was significantly increasing in PD patients with high NLR, which may have a certain guiding significance for the clinic. [ABSTRACT FROM AUTHOR]

Introduction: Though neutrophil/lymphocyte ratio (NLR) level appears to be related with stroke events in general population, its relationship with stroke in peritoneal dialysis (PD) patients is still uncertain. This study aims to investigate the association between NLR and the first occurrence of stroke in PD patients.Methods: In this retrospective cohort study, 1507 PD patients were enrolled from four centers in China and stratified into tertiles of NLR levels. The incidence of the first occurrence of stroke was analyzed by Kaplan-Meier cumulative incidence curve among different NLR tertiles, competing risk analysis was used to calculate the incidence of the first occurrence of stroke in the presence of competing risk of other events, multivariable COX regression analysis was performed to estimate the hazard ratios (HRs) for the first occurrence of stroke, as well as forest plot was utilized to describe the relationship between NLR and the first occurrence of stroke in different subgroups.Results: During follow-up, 84 new-onset stroke events were recorded. Kaplan-Meier cumulative incidence curves showed significant differences in the incidence of the first occurrence of stroke among three groups (log-rank test: P < .001). In competing risk analysis, the cumulative incidence curves for tertiles of NLR levels were highly significant for the first occurrence of stroke (P < .001), but they were not statistically different for the occurrence of other events. Compared to the lowest tertile of NLR level, the highest tertile was associated with increased risk of the first occurrence of stroke in the adjusted Cox model (HR = 2.39, 95% CI: 1.37 to 4.15; P < .05). As for forest plot, there was no interaction in all subgroups.Conclusion: High NLR was an independent risk factor for the first occurrence of stroke in PD patients. [ABSTRACT FROM AUTHOR]

Background. Although mean platelet volume (MPV) appears to be associated with poor outcome of pneumonia, the relationship between MPV and in-hospital mortality is unclear in severe pneumonia (SP) patients. Methods. In this retrospective cohort study, 115 SP patients from June 1st, 2016, to September 29th, 2019, were included and divided into two groups. The primary outcome was in-hospital mortality. The receiver operating characteristic (ROC) curve was performed to assess the predictive ability for in-hospital mortality. Kaplan-Meier cumulative incidence curves were applied to observe the incidence of mortality. Multivariable Cox regression analyses were used to evaluate the hazard ratios (HRs). Besides, a formal test for interaction was investigated to analyze the relationship between MPV and sex. Results. During the course of hospitalization, 63 cases of mortality were recorded. ROC analysis suggested that MPV had a modest power for predicting in-hospital mortality (AUC = 0.723 , 95% CI: 0.628-0.818, P < 0.001). Yet the cutoff value of MPV was 10.5 (sensitivity = 73.02 %; specificity = 73.08 %). Compared to the low-MPV group, the high-MPV group had significantly increased in-hospital mortality (log-rank test = 13.501 , P < 0.001), while the adjusted Cox model indicated that the high-MPV group was associated with an elevated risk of in-hospital mortality (HR: 2.267, 95% CI: 1.166-4.406, P = 0.016). Moreover, analyses of in-hospital mortality suggested a significant interaction between optimal MPV level and sex (P = 0.011). In a multivariate Cox model which included females only, a high MPV level was associated with increased risk of in-hospital mortality (HR: 11.387, 95% CI: 1.767-73.380, P = 0.011). Conclusion. High MPV level is an independent risk factor for in-hospital mortality in patients with SP. [ABSTRACT FROM AUTHOR]

Background. Neutrophil to lymphocyte ratio (NLR) is a new inflammatory marker; the relationship between NLR and adverse cardiovascular (CV) prognosis has been gradually emphasized in the general population. However, their association in peritoneal dialysis (PD) patients remains unclear. Methods. From January 1, 2010, to May 31, 2017, a total of 1652 patients were recruited. NLR was categorized in triplicates: NLR ≤ 2.74 , 2.74 < NLR ≤ 3.96 , and NLR > 3.96. Kaplan-Meier cumulative incidence curve and multivariable COX regression analysis were used to determine the relationship between NLR and the incidence of adverse CV outcome, while a competitive risk model was applied to assess the effects of other outcomes on adverse CV prognosis. Besides, forest plot was investigated to analyze the adverse CV prognosis in different subgroups. Results. During follow-up, 213 new-onset CV events and 153 CV disease (CVD) deaths were recorded. Multivariable COX regression models showed that the highest tertile of NLR level was associated with increased risk of CV events (HR = 1.39 , 95 % CI = 1.01 ‐ 1.93 , P = 0.046) and CVD mortality (HR = 1.81 , 95 % CI = 1.22 ‐ 2.69 , P = 0.003), while compared to the lowest tertile. Competitive risk models showed that the differences in CV event (P < 0.001) and CVD mortality (P = 0.004) among different NLR groups were still significant while excluding the effects of other outcomes. In subgroups, with each 1 increased in the NLR level, adjusted HR of new-onset CV event was 2.02 (95 % CI = 1.26 − 3.23 , P = 0.003) and CVD mortality was 2.98 (95 % CI = 1.58 − 5.62 , P = 0.001) in the younger group (age < 60 years). Conclusions. NLR is an independent risk factor for adverse CV prognosis in PD patients younger than 60 years old. [ABSTRACT FROM AUTHOR]

Zhuyu pill (ZYP), an effective prescription of traditional Chinese medicine, is composed of Coptis chinensis Franch. and Tetradium ruticarpum (A. Jussieu) T. G. Hartley and has shown potential anticholestatic effects. However, its mechanism of action in treating cholestasis remains unclear. Since post-transcriptional control of mRNA by micro-RNAs (miRNAs) represents an important mechanism of gene regulation, it is promising to explore this in relation to ZYP and cholestasis. To confirm the anticholestatic effect of ZYP and to explore its potential biological mechanism. In this study, a cholestasis rat model was induced by α-naphthyl-isothiocyanate (ANIT, 50 mg/kg) and treated with ZYP (low dose: 0.6 g/kg, high dose: 1.2 g/kg). Serum biochemistry indices and liver histopathology were used to evaluate the model and efficacy, and miRNA sequencing was used to measure differences in miRNA expression in the liver between the control, model, low-dose ZYP, and high-dose ZYP groups. To verify the accuracy of sequencing results and explore the potential anti-cholestasis mechanism of ZYP, RT-PCR was used to identify differentially expressed miRNAs and their target genes. Both high- and low-dose ZYP exhibited significant anticholestatic effects, with the high-dose showing better effects than low-dose ZYP. Additionally, four differentially expressed miRNAs, rno-miR-147, rno-miR-20b-5p, rno-miR-29b-3p, and rno-miR-3586-3p, were found to be upregulated in cholestasis and downregulated after ZYP intervention. Eight target genes of the above miRNAs, including ABCG8, CLOCK, PLEC, SLC4A2, NEB, ADAMTS12, TTN and FAM174B were inhibited in cholestatic rats, exhibiting up-regulated expression tendencies after ZYP intervention, and the expression tendencies were significant negatively correlated with serum biochemical indices. ZYP can significantly reduce liver biochemical indices and improve liver tissue damage in cholestasis rats through the regulation of miRNA expression in the liver, producing a positive regulatory effect on bile excretion-related genes. [Display omitted] • The Zhuyu pill has a reliable anti-cholestasis effect. • The anti-cholestasis effect of the Zhuyu pill is related to the regulation of miRNA expression. • By inhibiting the expression of miRNAs, ZYP regulates the expression of target genes and produces an anti-cholestasis effect.. [ABSTRACT FROM AUTHOR]

Multi infarct dementia (MID) is a form of dementia that is preventable and treatable. However, at present, the drugs used in MID treatment were developed for Alzheimer's disease. While only a limited range of drugs is available, the incidence of MID is increasing year on year. The present study aimed to investigate the effect and underlying mechanisms of a combination of ginsenosides and astragalosides (CGA) on cognitive decline in rats with MID. A rat model of MID was established using micro-thromboembolism, and the behavioral changes in the rats were evaluated using the Morris water maze and open field tests at 60 days post-CGA intervention. The pathological morphology of the hippocampal CA1 area was observed using hematoxylin and eosin staining. The contents of ATP, ADP and AMP were determined using high-performance liquid chromatography. Mitochondrial swelling and changes in the membrane potential in the hippocampus were detected using flow cytometry, and the changes in insulin, glutamate and γ-aminobutyric acid (GABA) content were detected using ELISA. Additionally, the expression of PI3K and AKT proteins was detected using western blot analysis. In a rat model of MID, CGA shortened the escape latency, increased the frequency of platform crossing, improved the disordered vertebral cell arrangement and reduced the cell number in the hippocampal CA1 area. CGA also reduced the degree of mitochondrial swelling, increased the mitochondrial membrane potential, and elevated the energy load and ATP content in the brain of rats with MID. Furthermore, CGA increased the insulin content and upregulated the expression of PI3K and AKT in the brain of rats with MID. In addition, in the rat model of MID, CGA also enhanced the movement time and the frequency of standing, and decreased the concentration of glutamate and GABA in the brain tissue. Amelioration of the cognitive decline in rats with MID by CGA was associated with its regulatory effect on the PI3K/AKT signaling pathway and neurotransmitter systems. [ABSTRACT FROM AUTHOR]

Background: Adipose-derived mesenchymal stem cells (ADSCs) have been extensively explored as a promising therapeutic agent due to their differentiation, proliferation and migration abilities. The epigenetic mechanisms that regulate the fate of mesenchymal stem cells (MSCs) have been described in detail. However, the epigenetic modulation of ADSCs proliferation and migration is poorly understood. Methods: The present study examined histone demethylases roles and expression by RT-PCR, as well as through siRNA screening and ChIP-qPCR assay. Cellular proliferation and migration assays were employed in shRNA-mediated JMJD6 knockdown and control ADSCs. PDE1C inhibition studies were conducted to confirm its role in JMJD6-mediated epigenetic regulation of ADSCs. Results: The data demonstrate that the histone demethylase JMJD6 plays a critical role in regulating the proliferation and migration of ADSCs by removing H4R3me2a at the promoter regions of PDEC1 and suppressing PDEC1 expression. Importantly, the depletion of JMJD6 in ADSCs significantly increased cellular proliferation and motility, which was associated with increases in PDE1C expression and decreases in the levels of both cAMP and cGMP. The increase in proliferation and migration was reversed by treatment with a PDE1C inhibitor, suggesting that JMJD6 attenuates the proliferation and migration of ADSCs as an epigenetic regulator and PDE1C partially contributes to the JMJD6-mediated regulation. Conclusions: Taken together, our results indicate for the first time that JMJD6 plays an important role in the regulation of ADSCs proliferation and migration through the modulation of PDE1C expression. [ABSTRACT FROM AUTHOR]

Rs1344706 in the the zinc finger protein 804A (ZNF804A) gene has been identified to be associated with schizophrenia and bipolar disorder (BD) in Europeans. However, whether rs1344706 is associated with schizophrenia in Chinese populations remains inconclusive; furthermore, the association between rs1344706 and BD in Chinese populations has been rarely explored. To explore the association between rs1344706 and schizophrenia/BD in Chinese populations, we genotyped rs1344706 among 1128 Chinese subjects (537 patients with BD and 591 controls) and found that rs1344706 showed marginal allelic association with BD (P = 0.028) with T-allele being more prevalent in cases than that in controls (OR = 1.19, 95% CI 1.03-1.37). Meta-analysis of rs1344706 by pooling all available data showed that rs1344706 was significantly associated with BD (P = 0.001). Besides, positive association of rs1344706 with schizophrenia was observed in Northern Chinese (P = 0.005). Furthermore, ZNF804A is highly expressed in human and mouse brains, especially in prenatal stage. [ABSTRACT FROM AUTHOR]