Association between alcohol consumption and sleep traits: observational and mendelian randomization studies in the UK biobank.

Previous studies have shown that excessive alcohol consumption is associated with poor sleep. However, the health risks of light-to-moderate alcohol consumption in relation to sleep traits (e.g., insomnia, snoring, sleep duration and chronotype) remain undefined, and their causality is still unclear in the general population. To identify the association between alcohol consumption and multiple sleep traits using an observational and Mendelian randomization (MR) design. Observational analyses and one-sample MR (linear and nonlinear) were performed using clinical and individual-level genetic data from the UK Biobank (UKB). Two-sample MR was assessed using summary data from genome-wide association studies from the UKB and other external consortia. Phenotype analyses were externally validated using data from the National Health and Nutrition Examination Survey (2017-2018). Data analysis was conducted from January 2022 to October 2022. The association between alcohol consumption and six self-reported sleep traits (short sleep duration, long sleep duration, chronotype, snoring, waking up in the morning, and insomnia) were analysed. This study included 383,357 UKB participants (mean [SD] age, 57.0 [8.0] years; 46% male) who consumed a mean (SD) of 9.0 (10.0) standard drinks (one standard drink equivalent to 14 g of alcohol) per week. In the observational analyses, alcohol consumption was significantly associated with all sleep traits. Light-moderate-heavy alcohol consumption was linearly linked to snoring and the evening chronotype but nonlinearly associated with insomnia, sleep duration, and napping. In linear MR analyses, a 1-SD (14 g) increase in genetically predicted alcohol consumption was associated with a 1.14-fold (95% CI, 1.07-1.22) higher risk of snoring (P < 0.001), a 1.28-fold (95% CI, 1.20-1.37) higher risk of evening chronotype (P < 0.001) and a 1.24-fold (95% CI, 1.13-1.36) higher risk of difficulty waking up in the morning (P < 0.001). Nonlinear MR analyses did not reveal significant results after Bonferroni adjustment. The results of the two-sample MR analyses were consistent with those of the one-sample MR analyses, but with a slightly attenuated overall estimate. Our findings suggest that even low levels of alcohol consumption may affect sleep health, particularly by increasing the risk of snoring and evening chronotypes. The negative effects of alcohol consumption on sleep should be made clear to the public in order to promote public health.

Efficient synthesis of rebaudioside D2 through UGT94D1-catalyzed regio-selective glycosylation.

Steviol glycosides have been widely applied as new sweeteners in food, beverages, health care, and daily chemical industry owing to the properties of high-intensity sweetness, low calorie, and good physiological characteristics. However, most of steviol glycosides have a bitter taste. Their organoleptic properties can be effectively improved by modifying the linked glycosyl units. In this study, UGT94D1, a uridine diphosphate-dependent glycosyltransferase from Sesamum indicum, was reported to selectively glycosylate rebaudioside A (Reb A) for the synthesis of rebaudioside D2 (Reb D2). Furthermore, a cascade reaction system was constructed to synthesize Reb D2 with 94.66% yield by coupling UGT94D1 with sucrose synthase AtSuSy from Arabidopsis thaliana. Thus, our study not only introduced a practical method for the synthesis of steviol glycosides but also provided the possibility for further exploration of Reb D2.

Doxycycline vs Placebo at 12 Weeks in Patients With Mild Thyroid-Associated Ophthalmopathy: A Randomized Clinical Trial.

Importance: Mild thyroid-associated ophthalmopathy (TAO) negatively impacts quality of life, yet no clinical guidelines for its treatment are available. Existing evidence supports the use of doxycycline in treating mild TAO. Objective: To evaluate the short-term (12 weeks) efficacy of doxycycline in treating mild TAO. Design, Setting, and Participants: In this placebo-controlled multicenter randomized double-masked trial, 148 patients were assessed for eligibility. After exclusions (patients who were pregnant or lactating, had an allergy to tetracyclines, or had uncontrolled systematic diseases), 100 patients with mild TAO (orbital soft tissue affected mildly) at 5 centers in China were enrolled from July 2013 to December 2019 and monitored for 12 weeks. Interventions: Participants were randomly assigned 1:1 to receive doxycycline (50 mg) or placebo once daily for 12 weeks. Main Outcomes and Measures: The primary outcome was the rate of improvement at 12 weeks compared with baseline assessed by a composite indicator of eyelid aperture (reduction ≥2 mm), proptosis (reduction ≥2 mm), ocular motility (increase ≥8°), and Graves ophthalmopathy-specific quality-of-life (GO-QOL) scale score (increase ≥6 points). Adverse events were recorded. Results: A total of 50 participants were assigned to doxycycline and 50 to placebo. The mean (SD) age was 36.7 (9.1) years; 75 participants (75.0%) were female and 100 (100.0%) were Asian. Medication compliance was checked during participant interviews and by counting excess tablets. At week 12, the improvement rate was 38.0% (19 of 50) in the doxycycline group and 16.0% (8 of 50) in the placebo group (difference, 22.0%; 95% CI, 5.0-39.0; P = .01) in the intention-to-treat population. The per-protocol sensitivity analysis showed similar results (39.6% [19 of 48] vs 16.0% [8 of 50]; difference, 23.6%; 95% CI, 6.4-40.8; P = .009). No adverse events other than 1 case of mild gastric acid regurgitation was recorded in either group. Conclusions and Relevance: The results of this study indicate that oral doxycycline, 50 mg daily, resulted in greater improvement of TAO-related symptoms at 12 weeks compared with placebo in patients with mild TAO. These findings support the consideration of doxycycline for mild TAO but should be tempered by recognizing the relatively short follow-up and the size of the cohort. Trial Registration: ClinicalTrials.gov Identifier: NCT02203682.

Systematic review and meta-analysis of probiotics in the treatment of allergic rhinitis.

BACKGROUND: The purpose of this meta-analysis is to systematically evaluate the efficacy of probiotics on allergic rhinitis (AR). METHODS: Collecting randomized controlled trials (RCTs) with probiotics as intervention measures for AR, two researchers independently screened the literature, extracted the data and evaluated the methodological quality of the included studies, and used RevMan 5.3 software for meta-analysis to observe the effects of probiotics on Rhinitis Quality of Life (RQLQ) scores, Rhinitis Total Symptom Scores (RTSS), blood eosinophil count, total and antigen-specific serum immunoglobulin E (IgE) levels by using the fixed- or the random-effects model to calculate the pooled risk for significant heterogeneity. RESULTS: A total of 2708 patients were included in 30 RCTs. Meta-analysis results showed that the RQLQ global scores (mean difference [MD] = -9.43; P < 0.00001), RQLQ nasal scores (MD = -1.52; P = 0.03), and RTSS nasal scores (MD = -1.96; P = 0.02) significantly improved in the probiotic group when compared with those in the placebo group. There was no significant difference in blood eosinophil count (MD = -0.09; P=0.82), RQLQ eye scores (MD = -1.45; P = 0.07), RTSS global scores (MD = -2.24; P = 0.26), RTSS eye scores (MD = -0.39; P = 0.31), total and antigen-specific serum IgE levels (MD = -0.04; P = 0.7 and MD = -0.08; P = 0.81) between the probiotic and the placebo group. CONCLUSION: Compared with the placebo group, the quality of life and symptoms of patients with AR significantly improved in the probiotic group, thus providing a new potential method for the application of probiotics in AR. However, because of the limited evidence for the current study outcomes, the heterogeneity of research, and the differences in research results, more high-quality studies are needed to in the future.

Laser decontamination microscopic process study on radioactive contaminations with Cs+ ion of 304 stainless steel surface.

The decommissioning of contaminated metal equipment in nuclear facilities may produce a wide range of radioactive waste. For metallic equipment like the primary loop, the radioactivity is mainly located in the oxide surface. Laser decontamination was performed on 304 stainless steel specimens with a stable isotope Cs contamination layer. Laser melting was used to create oxide layer on the surface of polished specimen for enhancing the penetration of Cs+ ion. The interaction between laser and matter (contamination, oxide and substrate) was studied by the stratification theory considering the difference in the thickness of contamination layer. At higher pulse duration (τp = 5ns), laser decontamination is mainly caused by thermal effects. The metal near oxide layer melts and vaporizes to form a molten pool and crater. For short pulse duration (τp = 1ns), the removal of surface contaminations mainly depends on thermal effect and stress wave, CsCl particles were removed by vaporization; however, oxide layer was stripped from the substrate in the form of solid fragment. For ultra-short pulse duration (τp = 150ps), the oxide layer has been partially ablated. Most of the heat absorbed by γ (austenite) is used for heating and evaporation to form porous structure, while the great mass of heat absorbed by M (martensite) is used for thermal diffusion. Therefore, the M regions only form a dynamic molten pool on its surface without vaporization.

New Insights of Corynebacterium kroppenstedtii in Granulomatous Lobular Mastitis based on Nanopore Sequencing.

BACKGROUND: The etiology of granulomatous lobular mastitis (GLM) remains unknown. This study aimed to detect bacteria in GLM using Nanopore sequencing and identify the relationship between GLM and Corynebacterium kroppenstedtii. METHODS AND MATERIALS: The bacterial detection on fresh samples (including breast pus and tissue) of 50 GLM patients using nanopore sequencing and culture methods. The bacterial detection rate of participants with different stages were compared and analyzed. Formalin-fixed and paraffin-embedded (FFPE) tissues from 39 patients were performed on Gram staining to identify Gram-positive bacilli (GPB) within lipid vacuoles. Moreover, the clinicopathological characteristics of GLM patients in different bacterial subgroups were also conducted. RESULTS: In 50 GLM patients, the detection rate of bacteria was 78% using nanopore sequencing method, especially in the early stage of GLM (over 80%), which was significantly higher than that using culture methods (24%, p < 0.001). The dominant bacteria were Corynebacterium species (64%), especially for the Corynebacterium kroppenstedtii. The detection rate of C. kroppenstedtii in nanopore sequencing method (56%) was higher than that in culture methods (16%, p < 0.001). Gram staining positive of bacteria in 7 patients, and 5 of them were C. kroppenstedtii. Thirty-one patients (31/39, 79.5%) exhibited typical histological structure of cystic neutrophilic granulomatous mastitis (CNGM), and eighteen patients detected with C. kroppenstedtii. CONCLUSION: Nanopore sequencing showed rapid and accurate bacteria detection over culture method in GLM patients. GLM is not sterile inflammation and closely related to C. kroppenstedtii. CNGM was associated with Corynebacterium infection, especially for C. kroppenstedtii.

Effect of Xingbi Gel Nasal Drops on Fyn-STAT5 Pathway in Nasal Mucosa Fibroblasts of Guinea Pigs with Allergic Rhinitis.

Fyn-STAT5 is considered to be the frontier signaling pathway of IgE-mediated allergic reactions related to mast cell activation, but research on allergic rhinitis (AR) has been rarely reported. Xingbi gel nasal drops (XGND) are a compound preparation of traditional Chinese medicine, which has the exact therapeutic efficacy on AR. The current study aimed to observe the effects of XGND on Fyn-STAT5 pathway in AR guinea pig nasal mucosal fibroblasts in vitro and further illuminate the possible therapeutic mechanism of XGND on AR. The isolated and cultured nasal mucosa fibroblasts from AR guinea pigs were identified by immunocytochemical staining. Real-time PCR and western blot were performed to detect the mRNA and protein levels of the Fyn-STAT5 pathway and related cytokines in AR guinea pig nasal mucosal fibroblasts. The results indicated that XGND may interfere with the Fyn-STAT5 pathway by reducing the expression of Fyn and SCF and upregulating STAT5 and IL-10, thereby inhibiting proliferation and degranulation of mast cells, correcting Th1/Th2 immune imbalance, and then alleviating the immune response of AR fibroblasts. Our study revealed the possible regulatory mechanism of XGND in AR and laid an experimental foundation for improving the clinical efficacy of AR and enriching the clinical medication for AR.

Effectiveness and safety of repetitive transcranial magnetic stimulation for the treatment of morphine dependence: A retrospective study.

ABSTRACT: Morphine dependence (MD) is a very common complication because of the chronic morphine consumption. Studies suggest that repetitive transcranial magnetic stimulation (rTMS) can be used for the treatment of MD. However, there is still lacking evidence to support rTMS for MD. Thus, this retrospective study aimed to investigate the effectiveness and safety of rTMS for patients with MD.In this retrosepctive study, a total of 100 patients with MD were included, and they were divided into a rTMS group (n = 50), and a control group (n = 50). All patients in both groups received occupational therapy. In addition, patients in the rTMS group received rTMS. All patients in both groups received a total of 8 weeks treatment. The outcomes comprised of morphine craving intensity, depression, anxiety, and sleep quality, which were appraised by Visual Analogue Scale (VAS), Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), and Pittsburgh Sleep Quality Index (PSQI), respectively. In addition, treatment-related adverse events were also considered for assessment.After 8 weeks treatment, patients in the rTMS group exerted better benefits in improving VAS (P < .01), SDS (P < .01), SAS (P < .01), and PSQI (P < .01), than patients in the control group. In addition, this study did not identify treatment-related adverse events in both groups.The findings of this study showed that rTMS treatment showed promising effectiveness on patients with MD. However, future studies should focus on warranting the present findings.

Value of contrast-enhanced malignancy imaging features in secondary grade diagnosis of BI-RADS-US type 4 breast lesions.

PURPOSE: To explore the value of contrast-enhanced malignancy imaging features in secondary grade diagnosis of Breast Imaging Reporting and Data System for Ultrasonography (BI-RADS-US) type 4 breast lesions. METHODS: After initial diagnosis by ultrasound, 124 BI-RADS-US type 4 patients with 130 lesions were examined by contrast-enhanced ultrasound (CEUS) and were classified again before surgery according to five contrast-enhanced malignancy imaging features: inhomogeneous enhancement, peripheral ring-like enhancement, expansive enhancement, internal filling defects, and surrounding radioactive convergence. Lesions with no contrast-enhanced features of malignancy were categorized as type 3; lesions with one, two, or three features of malignancy were categorized as type 4A, 4B, or 4C, respectively; and lesions with four or more indices of malignancy were categorized as type 5. The value of contrasted imaging features of malignancy in diagnosing BI-RADS-US type 4 breast lesions was analyzed. RESULTS: The accuracy of CEUS diagnosis for type 3 lesions was 93.8% (46/49), 76.9% (10/13) for type 4A, 71.4% (5/7) for type 4B, 75.0% (9/12) for type 4C, and 93.8% (46/49) for type 5 lesions. The sensitivity of CEUS in diagnosing malignant lesions was 90.4%, specificity was 83.6%, and accuracy was 86.9%. CEUS decreased the benign lesion biopsy ratio to 68.5% (46/67) and increased the diagnosis ratio of malignant lesions to 73.0% (46/63). CONCLUSIONS: CEUS can further optimize the classification of BI-RADS-US type 4 breast lesions and may provide a better reference basis for clinical diagnosis and treatment of those breast lesions.

Decreased modulation of segregated SEEKING and selective attention systems in chronic insomnia.

Sleep-related attentional bias and instinctual craving-sleep status may be associated with value-driven selective attention network and SEEKING system. We hypothesized that the two networks might be important components and underlie etiology of inability to initiate or/and maintain sleep in patients with chronic insomnia (PIs). Our aim is to investigate whether frequency-frequency couplings(temporal and spatial coupling, and differences of a set of imaging parameters) could elevate the sensibility to characterize the two insomnia-related networks in studying their relationships with sleep parameters and post-insomnia emotions. Forty-eight PIs and 48 status-matched good sleepers were requested to complete sleep and emotion-related questionnaires. Receiver operating characteristic curve was used to calculate the discriminatory power of a set of parameters. Granger causality and mediating causality analysis were used to address the causal relationships between the two networks and sleep/emotion-related parameters. Frequency-frequency couplings could characterize the two networks with high discriminatory power (AUC, 0.951; sensitivity, 87.5%; specificity, 95.8%), which suggested that the frequency-frequency couplings could be served as a useful biomarker to address the insomnia-related brain networks. Functional deficits of the SEEKING system played decreased mediator acting in post-insomnia negative emotions (decreased frequency-frequency coupling). Functional hyperarousal of the value-driven attention network played decreased mediator acting in sleep regulation (increased frequency-frequency coupling). Granger causality analysis showed decreased causal effect connectivity between and within the two networks. The between-network causal effect connectivity segregation played decreased mediator acting in sleep regulation (decreased connectivity). These findings suggest that the functional deficits and segregation of the two systems may underlie etiology of PIs.

A network pharmacology strategy to investigate the anti-inflammatory mechanism of luteolin combined with in vitro transcriptomics and proteomics.

Luteolin, a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we systematically investigated druggability and anti-inflammatory mechanism of luteolin based on network pharmacology and in vitro experiments. The absorption, distribution, metabolism and excretion of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiments were carried out to estimate the accuracy of predicted target genes. ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform anti-inflammatory effect.

Development of a risk-stratification scoring system for predicting lymphovascular invasion in breast cancer.

BACKGROUND: Lymphovascular invasion (LVI) is a vital risk factor for prognosis across cancers. We aimed to develop a scoring system for stratifying LVI risk in patients with breast cancer. METHODS: A total of 301 consecutive patients (mean age, 49.8 ± 11.0 years; range, 29-86 years) with breast cancer confirmed by pathological reports were retrospectively evaluated at the authors' institution between June 2015 and October 2018. All patients underwent contrast-enhanced Magnetic Resonance Imaging (MRI) examinations before surgery. MRI findings and histopathologic characteristics of tumors were collected for analysis. Breast LVI was confirmed by postoperative pathology. We used a stepwise logistic regression to select variables and two cut-points were determined to create a three-tier risk-stratification scoring system. The patients were classified as having low, moderate and high probability of LVI. The area under the receiver operating characteristic curve (AUC) was used to evaluate the discrimination ability of the scoring system. RESULTS: Tumor margins, lobulation sign, diffusion-weighted imaging appearance, MRI-reported axillary lymph node metastasis, time to signal intensity curve pattern, and HER-2 were selected as predictors for LVI in the point-based scoring system. Patients were considered at low risk if the score was < 3.5, moderate risk if the score was 3.5 to 6.0, and high risk if the score was ≥6.0. LVI risk was segmented from 0 to 100.0% and was positively associated with an increase in risk scores. The AUC of the scoring system was 0.824 (95% confidence interval [CI]: 0.776--0.872). CONCLUSION: This study shows that a simple and reliable score-based risk-stratification system can be practically used in stratifying the risk of LVI in breast cancer.

Xingbi Gel Ameliorates Allergic Rhinitis by Regulating IFN-γ Gene Promoter Methylation in CD4+ T Cells via the ERK-DNMT Pathway.

Allergic rhinitis (AR) is a common, non-infectious, chronic nasal mucosal disease primarily mediated by immunoglobulin E (IgE) following allergen exposure. Currently, studies on AR mainly focus on cytokines, IgE and its receptors, basophils, eosinophils, mast cells, and related genes. Among these, an imbalance between T helper (Th) 1 and Th2 cells is considered an important mechanism underlying AR pathogenesis. The most important cytokines in AR are interleukin (Il)-4 and interferon gamma (IFN-γ) which are secreted by Th2 and Th1 cells, respectively. Il-4 and IFN-γ are antagonistic to each other in regulating IgE synthesis. In this study, the expression of extracellular signal-regulated protein kinase (ERK) 1/2 and its phosphorylation from p-ERK1/2, were significantly increased in a cluster of differentiation of 4+ T cells of AR mice, suggesting that the ERK signaling pathway in these cells is involved in the occurrence and development of AR. This result also implies an enhanced expression of deoxyribonucleic acid methyltransferases (DNMTs). To verify the relationship between ERK signaling and DNMT expression, AR mice were treated with PD98059, a specific inhibitor of the ERK1/2 signaling pathway. The results revealed that perturbations in ERK signaling were significantly positively correlated with the downregulation of DNMT1 expression. Pharmacological intervention is key to treating AR. This study demonstrated that Xingbi gel intervention affected both serum IgE levels and AR behavior scores in mice. Based on its effects on IFN-γ gene expression, the regulation of Th1/Th2 balance, and the ERK signaling pathway, research on the effects of Xingbi gel on AR may provide new avenues in its prevention and treatment.

[The third-generation sequencing combined with targeted capture technology for high-resolution HLA typing and MHC region haplotype identification].

The high-resolution and accurate typing of human leukocyte antigen (HLA) is of great significance for the study of tissue matching in organ transplantation and the correlation between HLA and disease. In this study, the peripheral blood of 12 patients with primary hepatocellular carcinoma was used to compare the advantages and disadvantages of the next- and third-generation sequencing technology for high-resolution HLA typing. In addition, probe capture technology was used to capture the MHC region of YH and HeLa standard cell lines, and a primary hepatocellular carcinoma patient. The captured products were sequenced using PacBio platform to assess the potential of ultra-long reads sequencing technology for analysis of the entire MHC region. Our results showed that: (1) the next- and third-generation sequencing technology can both achieve 6-8 digit high resolution in HLA typing. However, the coverage of the third-generation is significantly better than the next-generation sequencing technology. (2) The ultra-long reads of the third generation sequencing can directly span the entire amplicon region, which has obvious advantages for haplotype phasing, with 92.79% of the HLA genes having accurate phasing results, which is much higher than the 75.65% from the next-generation data. (3) The long-reads from the third generating sequencing can not only be used to assemble the MHC region but also the ability to phase the entire MHC region of 3.6 Mb, thereby helping to clarify the localization information of the mutation sites, alleles and non-coding regions on each MHC haplotype, and providing a theoretical basis for the study of immune and other related diseases.

Increased salivary fluid flow in children with newly diagnosed allergic rhinitis.

OBJECTIVES: The pathogenesis of allergic rhinitis (AR) may involve dysregulation of the autonomic nervous system (ANS). Salivary fluid flow and salivary alpha-amylase (sAA) secretion are able to reflect the activity of parasympathetic (PNS) and sympathetic nervous system (SNS), respectively. The study aims to address the ANS profile in children with newly diagnosed AR by measuring the salivary secretion pattern. METHODS: We recruited thirty-three children with newly diagnosed AR and thirty-one age- and sex-matched healthy children as control. Saliva samples were collected in the morning and the salivary parameters, including salivary flow rate (SFR, ml/min) and sAA secretion rate (µg/min), were determined accordingly. We also measured the gene copy number of the sAA gene, AMY1, for each individual. RESULTS: We detected a significantly higher SFR in AR children compared with healthy control (2.20 ±â€¯0.55 vs. 1.63 ±â€¯0.61; p = 0.0002). Similar sAA secretion rate was observed between the two groups (312.8 ±â€¯124.8 (Healthy) vs. 347.9 ±â€¯114.0 (AR) µg/min; p = 0.2444). Besides, the two groups did not differ in AMY1 gene copy number (7.2 ±â€¯2.3 (Healthy) vs. 7.7 ±â€¯2.2 (AR); p = 0.3493). CONCLUSIONS: Our results implicate an overactivity of the PNS while normal SNS activity in children with newly diagnosed AR. The findings support a contributing role of the ANS dysfunction in the pathogenesis of AR.

Analysis of gene mutation sites in patients with failed anti-HIV-1 treatment in Lincang City from 2011 to 2018 / 中华疾病控制杂志

Objective To understand the major genotype-resistant mutation sites and change trends of HIV/AIDS patients with failure of antiviral therapy (ART) in Lincang City, Yunnan Province. Methods The In-House method was used to amplify the Pol gene region in the plasma samples of HIV/AIDS patients with failure of ART in Lincang City from 2011 to 2018. The target sequence was spliced and submitted to the HIV resistance database to identify and analyze the HIV-1 subtypes and resistant mutation sites. Results The 950 strains of HIV/AIDS patients with antiviral failure were mainly CRF08_BC, accounting for 75.5% (717/950), and the total gene mutation rate was 67.1% (637/950), which was dominated by non-nucleoside reverse transcriptase inhibitors (NNRTIs), accounting for 62.4% (593/950); followed by nucleoside reverse transcriptase inhibitors (NRTIs), accounting for 34.7% (330/950); protease inhibitors (PIs) was 7.5% (71/950). A total of 15 NRTIs of resistance-related mutation sites were detected, mainly M184V (29.3%) which was detected mostly in AZT/D4T+3TC+NVP programs; including 17 kinds of NNRTIs, mainly was K103N/S (25.1%)，the most detected in AZT/TDF+3TC+EFV programs. There were 22 kinds of PIs，mainly secondary sites were L10F/V/I (2.2%) and L33F (2.1%). The top three NRTIs mutation sites in the area were changed from T69D/N/G，M184I/V and D67N/G/S to M184I/V, K70R/Q/E/T and T215Y/F/V/I/N/A/D. NNRTIs mutation sites were changed from V179D/T/E/F, E138A/K/G/R and Y181C/F/G/V to K103N/S, E138A/K/G/R and V179D/T/E/F. The mutation sites of the first three PIs did not change much. Conclusions The second-line regimen based on PIs is a better choice in free antiviral treatments. Mastering the drug resistance of different gene mutations is beneficial to the compatibility of first-line drugs, thus delaying the use of second-line drugs.

Urinary proteomics analysis based on mass spectrometry and identification of therapeutic targets of Shenkangling interventions in rats with adriamycin nephropathy using iTRAQ.

OBJECTIVE: The isobaric tags for relative and absolute quantification (iTRAQ) technique for proteomic analysis was employed to identify diagnostic markers and therapeutic targets of Shenkangling intervention or prednisone tablets in rats with adriamycin nephropathy (AN). METHODS: Fifty healthy, clean-grade Sprague-Dawley rats were selected, with 10 rats in the normal group and the remaining 40 rats receiving a tail vein injection of 5.5 mg/kg of adriamycin (ADR) to induce AN. Treatment began 1 week later. The normal group received gastric administration of normal saline. Forty rats with induced AN were further randomly divided into the AN modeling group (n = 10), AN modeling + prednisone treatment group (n = 10), AN modeling + Shenkangling intervention group (n = 10), and AN modeling + prednisone + Shenkangling intervention group (n = 10). iTRAQ was employed in combination with mass spectrometry to analyze the differentially expressed proteins in the urine after 3 weeks of treatment (in the fourth week of the experiment). RESULTS: Compared with normal rats, AN rats had 6 down-regulated proteins and 1 upregulated protein. Compared with AN rats, prednisone rats had 2 down-regulated and 6 upregulated proteins. Compared with AN rats, combined treatment rats had 2 down-regulated and 8 upregulated proteins. Compared with the AN model group, the Shenkangling treatment group had 3 down-regulated and 9 upregulated proteins. Gro, Afamin, Cystatin-related protein 2, Afamin, and isoform CRA_a were considered diagnostic markers of primary nephrotic syndrome (PNS). Telomerase was considered the therapeutic target of prednisone. Urinary protein 2, Apolipoprotein A-II, 45 kDa calcium-binding protein, Vitronectin, and Osteopontin were the therapeutic targets of the Shenkangling intervention. Afamin, isoform CRA_a, Apolipoprotein A-IV, Coagulation factor XII, Prolactin-induced protein, and Coagulation factor XII were the therapeutic targets of the Shenkangling intervention combined with prednisone. CONCLUSION: The feasibility of urinary proteomics analysis in rats using a large number of proteins with finite molecular weights is controversial. The markers screened in this study may be of clinical value for the diagnosis and treatment of nephropathy. However, these findings should be confirmed in future cohort studies.

Similarities and Differences in Psychology.

Addiction is marked by repeating a certain behavior while ignoring the potential physical or mental consequences. Non-substance addiction provides an ideal model for researching the emergence and development of addiction's basic mechanism. Comparative studies of substance and non-substance addiction are helpful to reveal the common basis of addiction development. This article explores this topic from a psychological angle, touching upon sensation seeking, inhibitory control, attentional bias, intertemporal choice and environment. A review of previous literature urges future research to propose a biopsychosocial model of addiction and consider addiction's effect on basic cognitive function alongside cognitive neuroscience technology.

Effects of Xingbi gel on leukotriene E4 and immunoglobulin E production and nasal eosinophilia in a guinea pig model for allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal airways.Many therapies do not have immediate effects,even which have side-effects.However,the effects of Xingbi gel for the treatment of AR was investigated. OBJECTIVE: We investigated the effects of Xingbi gel on serum levels of leukotriene E4 (LTE4) and immunoglobulin E (IgE), as well as eosinophil counts in the nasal mucosa using a guinea pig model of allergic rhinitis (AR). METHODS: In addition to a healthy control group without AR, guinea pigs with AR were randomly divided into untreated AR control group, low-dose Xingbi gel (0.2483 g/mL) group, high-dose Xingbi gel (0.4966 g/mL) group, and budesonide group. RESULTS: Compared to the healthy controls, untreated AR guinea pigs had significantly higher ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts (p <0.01). Treatments with low-dose Xingbi gel, high-dose Xingbi gel, and budesonide significantly reduced the ethology scores, serum LTE4 and IgE levels, and nasal mucosa eosinophil counts as compared to untreated AR model guinea pigs (p <0.01). CONCLUSION: Xingbi gel alleviates AR in part through inhibiting LTE4 and IgE production and reducing eosinophilia in the nasal mucosa.