Haplotype analysis of long-chain non-coding RNA NONHSAT102891 promoter polymorphisms and depression in Chinese individuals: A case-control association study.

BACKGROUND: Our previous study reported that the single-nucleotide polymorphism (SNP) rs155979 GC in the promoter region of long-chain non-coding RNA (lncRNA) NONHSAT102891 affects depression susceptibility in a Chinese population. AIM: To explored associations of two SNPs and haplotypes in the lncRNA NONHSAT102891 promoter region with depression susceptibility in Chinese population. METHODS: This this case-control association study was approved by the Ethics Committee of Chengdu Medical College (approval number: 201815). Patient diagnosis was based on DSM-IV criteria. We selected a total of 480 patients with depression and 329 healthy controls with no history of psychopathology, and performed genotyping of two SNPs by extracting peripheral venous blood samples from the subjects. The function of the two lncRNA NONHSAT102891 promoter G/C and A/T haplotypes was detected by dual-luciferase reporter assays of human embryonic kidney 293T transfected cells. RESULTS: Stratified analysis of clinical and genotypic characteristics of our cohort showed that the degree of mild depressive episodes associated with the rs6230 TC/CC genotype increased by 1.59 times [TC/CC vs TT: odds ratio (OR) = 1.59, 95% confidence interval (CI): 1.08-2.35, P = 0.019]. The haploid analysis revealed linkage disequilibrium between rs3792747 and rs6230, and the double SNP CG haplotype was more common in the control group compared to case group, indicating that this haplotype significantly reduced the risk of depression (C/G vs T/A: OR = 0.42, 95%CI: 0.21-0.83, P = 0.01). There was no significant difference in the dual-luciferase reporter activity of the G/C and A/T haplotypes compared with the control group (P > 0.05), indicating that the double SNP haplotype has no transcriptional activity. CONCLUSION: The rs3792747 and rs6230 CG haplotypes of the lncRNA NONHSA T102891 promoter may be related to a reduced risk of depression in the Han Chinese population.

Interactions Between Body Mass Index and Glomerular Filtration Rate Increase the Identification Ability of Obstructive Sleep Apnea in Patients with Hypertrophic Cardiomyopathy.

Purpose: Obstructive sleep apnea (OSA) is common in hypertrophic cardiomyopathy (HCM) patients and is related to worse adverse prognosis in HCM patients. However, there are no acknowledged warning characteristics to help to identify OSA in HCM patients. Methods: Seventy-one HCM patients and forty-nine hypertensive (HTN) patients as control group underwent polysomnography (PSG) examination at the Second Affiliated Hospital of Nanchang University from January 2015 to December 2019 patients were consecutively enrolled. The characteristics were analyzed and compared between HCM patients with OSA and without OSA. Results: A total of 37 (52%) HCM patients and 25 (51%) HTN patients were diagnosed with OSA. High body mass index (BMI) (OR = 1.228, 95% CI: 1.032,1.461, P = 0.020) and low estimated glomerular filtration rate (eGFR) (OR = 0.959, 95% CI: 0.931,0.989, P = 0.007) independently correlated with the occurrence of OSA in HCM patients, respectively. Multiplicative interaction was shown between high BMI and low eGFR on the risk of OSA in HCM patients (OR: 6.050, 95% CI: 1.598, 22.905, P = 0.008). The additive interaction analysis further suggested that 70.1% of HCM patients developed OSA due to the additive interaction between BMI and eGFR. The identification ability of OSA in HCM patients was significantly enhanced by using both BMI and eGFR (area under receiver-operating characteristic analysis curve 0.785; P = 0.000038) as compared with BMI (area under curve 0.683, P = 0.008) or eGFR (area under curve 0.700, P = 0.004), respectively. Conclusion: High BMI or low eGFR independently related to the occurrence of OSA in HCM patients, and the multiplicative and additive interactions between BMI and eGFR increased the identification ability of OSA in HCM patients.

Application of lanthanide-doped upconversion nanoparticles for cancer treatment: a review.

With the excellent ability to transform near-infrared light to localized visible or UV light, thereby achieving deep tissue penetration, lanthanide ion-doped upconversion nanoparticles (UCNP) have emerged as one of the most striking nanoscale materials for more effective and safer cancer treatment. Up to now, UCNPs combined with photosensitive components have been widely used in the delivery of chemotherapy drugs, photodynamic therapy and photothermal therapy. Applications in these directions are reviewed in this article. We also highlight microenvironmental tumor monitoring and precise targeted therapies. Then we briefly summarize some new trends and the existing challenges for UCNPs. We hope this review can provide new ideas for future cancer treatment based on UCNPs.

High mobility group box-1 serves a pathogenic role in spinal cord injury via the promotion of pro-inflammatory cytokines.

Traumatic spinal cord injury (SCI) is a devastating condition marked by permanent motor, sensory, and autonomic dysfunction, in which the inflammatory response serves an important and preventable role. High mobility group box-1 (HMGB1) is a potent regulator of inflammation in numerous acute and chronic inflammatory conditions.; however, the role of HMGB1 in SCI remains unclear. The present study aimed to characterize the temporal dynamics of HMGB1 release after SCI, to investigate the role of spinal microglia activation in mediating the effects of HMGB1 on SCI, and to explore the therapeutic potential of intrathecal anti-HMGB1 polyclonal antibody on alleviating SCI. The present study demonstrated that HMGB1 expression was increased immediately after traumatic injury of a primary spinal neuron culture. It was found that neutralizing HMGB1 significantly ameliorated SCI pathogenesis and hind limb paralysis. Moreover, the levels of a number of pro-inflammatory cytokines in the SCI lesion were reduced when local HMGB1 was blocked by anti-HMGB1 antibody. In addition, the injured neuron-derived conditioned medium increased TNF-α secretion and the NF-κB pathway in the BV2 microglia cell line via HMGB1. Collectively, these results indicated that HMGB1 served an important role in SCI inflammation and suggested the therapeutic potential of an anti-HMGB1 antibody for SCI.

A Clinical-Radiomic Nomogram Based on Unenhanced Computed Tomography for Predicting the Risk of Aldosterone-Producing Adenoma.

PURPOSE: To develop and validate a clinical-radiomic nomogram for the preoperative prediction of the aldosterone-producing adenoma (APA) risk in patients with unilateral adrenal adenoma. PATIENTS AND METHODS: Ninety consecutive primary aldosteronism (PA) patients with unilateral adrenal adenoma who underwent adrenal venous sampling (AVS) were randomly separated into training (n = 62) and validation cohorts (n = 28) (7:3 ratio) by a computer algorithm. Data were collected from October 2017 to June 2020. The prediction model was developed in the training cohort. Radiomic features were extracted from unenhanced computed tomography (CT) images of unilateral adrenal adenoma. The least absolute shrinkage and selection operator (LASSO) regression model was used to reduce data dimensions, select features, and establish a radiomic signature. Multivariable logistic regression analysis was used for the predictive model development, the radiomic signature and clinical risk factors integration, and the model was displayed as a clinical-radiomic nomogram. The nomogram performance was evaluated by its calibration, discrimination, and clinical practicability. Internal validation was performed. RESULTS: Six potential predictors were selected from 358 texture features by using the LASSO regression model. These features were included in the Radscore. The predictors included in the individualized prediction nomogram were the Radscore, age, sex, serum potassium level, and aldosterone-to-renin ratio (ARR). The model showed good discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.900 [95% confidence interval (CI), 0.807 to 0.993], and good calibration. The nomogram still showed good discrimination [AUC, 0.912 (95% CI, 0.761 to 1.000)] and good calibration in the validation cohort. Decision curve analysis presented that the nomogram was useful in clinical practice. CONCLUSIONS: A clinical-radiomic nomogram was constructed by integrating a radiomic signature and clinical factors. The nomogram facilitated accurate prediction of the probability of APA in patients with unilateral adrenal nodules and could be helpful for clinical decision making.

Periodontal disease and emotional disorders: A meta-analysis.

OBJECTIVE: The objective of this study was to evaluate the relationship of periodontal disease with depression and anxiety via a systematic review and meta-analysis. METHOD: We systematically searched the EMBASE, PubMed, Web of Science, PsycINFO, and SinoMed databases (until August 4, 2019) with language restricted to English and Chinese. Case-control, cross-sectional, and cohort studies that calculated the risk ratio (RR), odds ratio (OR)/prevalence OR (POR), and hazard ratio (HR) of depression/anxiety with periodontal disease or the OR/POR/RR/HR of periodontal disease caused by depression/anxiety were included. Observational studies that reported the depression/anxiety scale score of patients with periodontal disease and healthy periodontal subjects aged ≥14 years were also included. We used the standard format to extract the following information from each included study: author/s, survey year, study design, age of participants, periodontal disease definition, depression/anxiety measurement, and summary of results. The Newcastle-Ottawa scale was used to ascertain the quality of the included citations. RESULTS: After screening, 40 studies were included. A meta-analysis of the case-control studies showed that periodontal disease was positively associated with depression (OR = 1.70, 95% confidence interval [CI] â€Š= 1.01-2.83). A meta-analysis of 12 studies showed that periodontal disease was significantly correlated with anxiety (OR = 1.36, 95% CI = 1.11-1.66). A meta-analysis of 18 studies showed that subjects with periodontal disease had higher depression scale score (standardized mean difference [SMD] = 1.05, 95% CI = 0.68-1.41) and anxiety scale score (SMD = 0.70, 95% CI = 0.44-0.96). CONCLUSION: Periodontal disease is associated with emotional disorders. However, the high degree of heterogeneity among studies should be considered. More high-quality prospective studies are required to confirm the relationship.

Porphyromonas gingivalis induces depression via downregulating p75NTR-mediated BDNF maturation in astrocytes.

Many cross-sectional epidemiological studies have shown the incidence of periodontitis is positive correlated with that of depression. However, their causal relationship and underlying mechanism are largely unknown. Porphyromonas gingivalis (Pg) is the main pathogen for periodontitis. Employing female mice treated with Pg every other day for 4 weeks, we found that Pg-mice showed obvious depression-like behavior, an increased number of activated astrocytes and decreased levels of mature brain derived neurotrophic factor (BDNF) and astrocytic p75NTR in the hippocampus. Both hippocampal injection of BDNF and overexpression of p75NTR in astrocytes alleviated Pg-induced depression-like behavior in mice. Moreover, Pg-lipopolysaccharides (LPS) generated similar phenotypes, which were reversed by the TLR-4 inhibitor TAK242. Our results suggest that Pg-LPS decreases the level of astrocytic p75NTR and then downregulates BDNF maturation, leading to depression-like behavior in mice. Our study provides the first evidence that Pg is a modifiable risk factor for depression and uncovers a novel therapeutic target for the treatment of depression.

Diltiazem augments the influence of MDR1 genotype status on cyclosporine concentration in Chinese patients with renal transplantation.

AIM: Co-administration of diltiazem can reduce the dosage of cyclosporine (CsA) in patients with renal transplantation. In this study, we investigated how diltiazem altered the relationship between MDR1 genetic polymorphisms and CsA concentration in Chinese patients with renal transplantation. METHODS: A total of 126 renal transplant patients were enrolled. All the patients received CsA (2-4 mg·kg(-1)·d(-1)), and diltiazem (90 mg/d) was co-administered to 76 patients. MDR1-C1236T, G2677T/A, and C3435T polymorphisms were genotyped. The whole blood concentration was measured using the FPIA method, and the adjusted trough concentrations were compared among the groups with different genotypes. RESULTS: In all patients, MDR1-C1236T did not influence the adjusted CsA trough concentration. With regard to MDR1-3435, the adjusted CsA trough concentration was significantly higher in TT carriers than in CC and CT carriers when diltiazam was co-administered (58.83±13.95 versus 46.14±7.55 and 45.18±12.35 ng/mL per mg/kg, P=0.011), and the differences were not observed in patients without diltiazam co-administered. With regard to MDR1-2677, the adjusted CsA trough concentration was significantly higher in TT carriers than in GG and GT carriers when diltiazam was co-administered (61.31±12.93 versus 52.25±7.83 and 39.70±7.26 ng/mL per mg/kg, P=0.0001). The differences were also observed in patients without diltiazam co-administered (43.27±5.95 versus 35.22±7.55 and 29.54±5.35 ng/mL per mg/kg, P=0.001). The adjusted CsA trough blood concentration was significantly higher in haplotype T-T-T and haplotype T-T-C carriers than in non-carriers, regardless of diltiazem co-administered. CONCLUSION: MDR1 variants influence the adjusted CsA trough concentration in Chinese patients with renal transplant, and the influence more prominent when diltiazem is co-administered.

CYP3A5*3 and MDR-1 C3435T single nucleotide polymorphisms in six Chinese ethnic groups.

The prevalent CYP3A5 *3 and the functional multi-drug resistance gene (MDR1) C3435T show marked interethnic variation among Orientals, Caucasians and Africans. This study aimed to investigate the distribution of CYP3A5*3 and MDR1 C3435T among Chinese ethnic groups. Genotypes of the CYP3A5*3 and MDR1 C3435T were determined in 839 unrelated healthy Chinese subjects by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. Frequencies (P < 0.05) of CYP3A5*3 variant alleles observed in Uygur Chinese, Kazakh Chinese and Tibetan Chinese (88.1%, 84.5% and 80.7%, respectively) were Significantly higher than those in Han Chinese, Wa Chinese and Bai Chinese (67.3%, 56.3% and 70.2%, respectively). Significantly higher 3435T variant frequencies (P < 0.05) were observed in Uygur Chinese (58.4%) and Kazakh Chinese (56.8%) compared with Han Chinese (44.2%), Tibetan Chinese (43.9%), Wa Chinese (45.8%) and Bai Chinese (44.2%). These results indicate that there were marked ethnic differences in the mutant frequencies of CYP3A5*3 and MDR1 C3435T among Chinese ethnic groups. Frequencies of those variants observed in Uygur Chinese, Kazakh Chinese, Tibetan Chinese, Wa Chinese and Bai Chinese wereintermediate between those seen in Han Chinese and African-American.

[Association between metabolic enzyme genotype of azathioprine and drug tolerance in patients with rheumatic diseases].

OBJECTIVE: To discuss the relationship between the genotype of thiopurine methyltransferase (TPMT) and azathioprine tolerance in the patients with rheumatic diseases. METHODS: Four common mutation alleles of TPMT in 200 patients with rheumatic diseases [TPMT*2 (G238C), TPMT*3A (A719G/G460A), TPMT*3B (G460A), TPMT*3C (A719G)] were detected by allele specific polymerase chain reaction (AS-PCR) and polymerase chain reaction-restriction fragment length polymorphism (PCR-PFLP). 194 patients who had used azathioprine finished the 3 months' follow-up. RESULTS: In the 200 patients with rheumatic diseases, 4 cases of heterozygote of TPMT*3C were detected, but no mutation of TPMT*2, TPMT*3B or TPMT*3A was found. The genotypic frequency of wild-type homozygote was 98%, and that of heterozygote (TPMT*1/TPMT*3C) was 2%. Mutation allele frequency in these patients was 1%. Average of TPMT activity of the 4 cases of heterozygote was (2.4 +/- 1.2) U/ml red blood cells, significantly lower than that of the 196 cases of homozygote which was (12.2 +/- 6.8) U/ml RBC. In the 194 patients who had used azathioprine, bone marrow suppression occurred in 18 patients, 2 of which suffered severe crisis of hematopoietic system, and 6 of which were complicated with impaired liver function. In the 4 patients with heterozygote, 3 had used azathioprine, and bone marrow suppression occurred within 1 month of using the drug, including 2 cases of severe crisis of hematopoietic system. CONCLUSION: Patients with mutation alleles of TPMT are intolerant to azathioprine, and likely to have severe crisis of hematopoietic system. To detect the TPMT genotype before using azathioprine is significant to improve the therapeutic safety.

[The profile and clinical significance of azathioprine metabolic enzymes activity in rheumatological patients].

OBJECTIVE: To detect the activity of thiopurine methyltransferase (TPMT) and its relationship with azathioprine (AZA) tolerance. METHODS: 200 patients of rheumatism need AZA were included in the study. RBC TPMT activity was detected with high performance liquid chromatography. Then the patients took AZA doses of 50 mg/d for the first month, 100 mg/d for the second month and 150 mg/d for the third month. RESULTS: TPMT activity of 200 patients ranged from 0.75 - 32.35 U/ml RBC, averaged (12.04 +/- 6.90) U/ml RBC. The activity of TPMT showed a normal skewness distribution and no activity deficiency was founded. 194 patients (97%) completed the 3 month follow-up. 18 showed bone marrow depression including 2 severe hematological crisis and 6 showed hepatic damage during the 3 months. Bone marrow depression was recorded of 7 cases with the TPMT activity of 2.24 - 5.97 U/ml RBC, averaged (3.47 +/- 1.21) U/ml RBC, among the dose of 50 mg/d and 11 cases with the TPMT activity of 4.01 - 11.17 U/ml RBC, averaged (7.08 +/- 2.58) U/ml RBC, among the dose of 100 - 150 mg/d. The other 176 cases did not show bone marrow depression at all, with TPMT activity of 4.47 - 32.35 U/ml RBC, averaged (13.02 +/- 6.07) U/ml RBC. TPMT activities in the 3 groups of patients were significantly different according to statistical analysis (P < 0.01). CONCLUSIONS: Hematological side effects were highly associated with TPMT activity in AZA usage. Patients with low TPMT activity should use low dose of AZA routinely, even though, toxicity may occur. Test of TPMT activity before AZA description was of significance.