Demographic and clinical factors correlated with clinical outcomes among people with HIV treated by antiretroviral therapy: a retrospective cohort study.

BACKGROUND: As is known, CD4 cell count is a significant parameter predicting HIV progression, opportunistic infections and death in HIV-infected individuals, as well was an important indicator for initiating antiretroviral therapy (ART). In China's National Free Antiretroviral Treatment Program, people with HIV (PWH) on ART can receive a CD4 count test at least once every six months. Importantly, the baseline CD4 count (before ART initiation) is significantly correlated with ART and even prognosis, but the influence of the peak CD4 cell count on ART and/or clinical outcomes is still unknown. METHODS: A retrospective study was conducted among 7965 PWH who received ART from October 2003 to September 2022 at Yunnan Infectious Disease Hospital. Clinical features and laboratory data were collected and analyzed by Chi-square test, univariate and multivariate Cox regression analysis. After elimination of confounding variables, multivariate Cox regression analysis was performed to identify survival-related factors. RESULTS: Of a total of 7965 PWH in the ART treatment cohort who met the inclusion and exclusion criteria, 7939 were finally included in the subsequent analyses. First, it was found that the proportion of clinical variables, including sex, age distribution, interval from diagnosis to ART initiation, marital status, and others, was significantly different between the living and dead groups (P < 0.05). Impressively, significantly more PWH had the higher level of baseline, peak and recent CD4 cell counts in the living group compared to those in the dead group. Due to multicollinearity effect, after excluding confounders, the following factors were found to be significantly associated with mortality by multivariate Cox regression analysis: (1) male sex (hazard ratio (HR) = 1.268 [1.032, 1.559]; P = 0.024); (2) time from HIV confirmation to ART initiation ≥ 6 months (HR = 1.962 [1.631, 2.360]; P < 0.001); (3) peak CD4 cell count: Peak CD4 < 100cells/µL group (HR = 16.093 [12.041, 21.508]; P < 0.001), 100cells/µL ≤ x < 200cells/µL group (HR = 7.904 [6.148, 10.160]; P < 0.001), 200cells/µL ≤ x < 350cells/µL group (HR = 3.166 [2.519, 3.980]; P < 0.001), 350cells/µL ≤ x < 500cells/µL group (HR = 1.668 [1.291, 2.155]; P < 0.001). CONCLUSION: Interestingly, patients in male, time from HIV confirmation to ART initiation ≥ 6 months, or peak CD4 count < 500 cells/µl had inferior clinical outcomes, in other word, a lower peak CD4 cell count significantly increased the risk of death, and peak CD4 cell was independent in predicting the overall survival of PWH. It is important to promote "early diagnosis and treatment of HIV" and regularly monitor CD4 levels in HIV/AIDS to evaluate the efficacy of ART and immune reconstitution, and optimize the ART regimen in time to further reduce the mortality of PWH.

Glycemic variability correlates with medial temporal lobe atrophy and decreased cognitive performance in patients with memory deficits.

Background: In the past, researchers have observed a significant link between glycemia and dementia. Medial temporal atrophy (MTA) is regarded as a common marker of dementia. The correlation between glycemic variability and MTA is unclear, and it has not been determined whether glycemic variability can be utilized as a biomarker of MTA and cognitive performance. Methods: The patients in a memory clinic who underwent brain MRI scans and cognitive assessments within the first week of their hospital visit, were enrolled. All participants underwent three fasting blood glucose and one HBA1c assessments on three self-selected days within 1 week of their first visit. The variability independent of the mean (VIM) was employed. Validated visual scales were used to rate the MTA results. The mini-mental state examination (MMSE) and Montreal Cognitive Assessment (MoCA) scales were employed to assess the cognitive functions of the participants. Spearman's correlation and regression models were used to examine the relationship between the MMSE and MoCA scales, and also determine the link between the MRI characteristics and cognitive status, where vascular risk factors, educational status, age, gender, and mean glucose parameters served as covariates. Results: Four hundred sixty-one subjects completed the MMSE scale, while 447 participants completed the MoCA scale. Data analysis revealed that 47.72% of the participants were men (220/461), and the median age of the patients was 69.87 ± 5.37 years. The findings of Spearman's correlation analysis exhibited a strong negative relationship between the VIM and MMSE score (r = -0.729, P < 0.01), and the MoCA score (r = -0.710, P < 0.01). The VIM was regarded as an independent risk factor for determining cognitive impairment in both the MMSE and MoCA assessments. The results were unaffected by sensitivity analysis. In addition, a non-linear relationship was observed between the VIM and MTA scores. Conclusion: The variability in the blood glucose levels, which was presented as VIM, was related to the reduced cognitive function, which was reflected by MMSE and MoCA scales. The relationship between the VIM and the MTA score was non-linear. The VIM was positively related to the MTA score when the VIM was less than 2.42.

Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy.

This retrospective case-control study examined the association between the rs2071559 (-604T/C) single nucleotide polymorphism (SNP) in the vascular endothelial growth factor receptor (VEGFR)-2 gene and the risk of diabetic retinopathy (DR) in Northern Han Chinese. This study included patients diagnosed with diabetes mellitus (DM) in Shijiazhuang between 07/2014 and 07/2016. The healthy controls were unrelated individuals who received routine physical examinations. The diabetic patients were grouped as DM (diabetes but no fundus examination abnormalities), proliferative DR (PDR), and non-proliferative DR (NPDR). Finally, 438 patients were included: 114 controls and 123, 105, and 96 patients in the DM, NPDR, and PDR groups, respectively. In the multivariable analyses and all genetic models, the VEGFR-2 rs2071559 SNP was not associated with DR (among all diabetic patients) or with PDR (among the patients with DR) after adjustment for age, sex, duration of DM, blood glucose, systolic blood pressure, diastolic blood pressure, and body mass index (all P > 0.05). In conclusion, the VEGFR-2- 604T/C rs2071559 SNP is not associated with DR or PDR in the Han Chinese population of Shijiazhuang (China).

Effects of Mixed Adding Crude Extracts of ß-Glucosidases from Three Different Non-Saccharomyces Yeast Strains on the Quality of Cabernet Sauvignon Wines.

The aim of this study was to investigate the effects of crude extracts of ß-glucosidase from Issatchenkia terricola SLY-4, Pichia kudriavzevii F2-24 and Metschnikowia pulcherrima HX-13 (termed as SLY-4E, F2-24E and HX-13E) on the flavor complexity and typicality of Cabernet Sauvignon wines. The grape must was fermented using Saccharomyces cerevisiae with single or mixed SLY-4E, F2-24E and HX-13E. The physicochemical characteristics, volatile aroma compounds, total anthocyanins and sensory attributes of the wines were determined. Adding SLY-4E, F2-24E and HX-13E in wines resulted in a decrease in the anthocyanin content, total acids and volatile acids in wines but an increase in the content of terpenes, benzene derivatives, higher alcohols and esters, which may enhance wine sensory qualities and result in loss of wine color. Different adding strategies of ß-glucosidase led to a variety of effects on wine aroma. S/H/F-Ew significantly increased the content of benzene derivatives, higher alcohols and long-chain fatty acid esters, which enhanced the fruity and floral flavor of wines. F2-24E significantly increased the content of short- and medium-chain fatty acid esters, acetate esters and carbonyl compounds. The results indicated that the mixed addition of non-Saccharomyces crude extracts and co-fermentation with S. cerevisiae could further improve wine flavor quality.

Meta-analysis of risk factors associated with suicidal ideation after stroke.

BACKGROUND: Over the past decade, increasing attention has been paid on post stroke suicide (PSS), which is one of complications of stroke. The rates of stroke and suicide are relatively high, especially in Asian populations. Thus, a deeper understanding of the prevalence and epidemiological impact of suicide after stroke is urgently needed. Clinical diagnosis and prevention of PSS are at the incipient stage, but the risk factors responsible for the occurrence of PSS in different regions and stages of the disease remain largely unknown. The present meta-analysis aimed to determine the incidence of PSS at different stages and time courses, and to identify the underlying risk factors for PSS. METHODS: We systematically searched the Cochrane library, Embase, PubMed, CNKI and Web of Science databases from their inception until April 2019.The research articles reporting on the risk factor for PSS were screened and included in the meta-analysis. The data from the included studies were extracted according to the predefined criteria. RESULTS: A total of 12 studies (n = 2,693,036) were included for meta-analyses. Of these studies, 7 reporting suicide prevalence were meta-analyzed. The pooled estimate of suicidal ideation rates after stroke was 12%, which could be influenced by multiple risk factors, including sex, smoking, depression, sleep disorders, previous stroke and low household income. Studies conducted in Asia demonstrated higher suicide prevalence (approximately 15%) compared to other regions. Smoking, low family income, depression, heart disease and sleep disorders were important risk factors for PSS. When compared to PSS of more than 1 year, the incidence of suicide within 1 year after stroke was more likely to be statistically significant. It was found that 4 out of every 1000 stroke survivors tended to commit suicide. The results of this meta-analysis showed that depression (OR = 2.32; p < 0.01) was significantly associated with suicidal ideation, regardless of stroke duration. CONCLUSION: PSS is one of the common complications of stroke. Despite some limitations, we successfully identified the risk factors associated with suicidal ideation after stroke. Notably, depression was significantly associated with suicidal ideation, regardless of stroke duration. Targeting this risk factor may be helpful to improve stroke patient care and prevent suicidal ideation after stroke. Future research will be carried out to assess whether suicidal ideation or thoughts and actual suicide attempts are strongly predictive of suicide deaths after stroke (Registration No. CRD42019128813).

Fire Acupuncture versus conventional acupuncture to treat spasticity after stroke: A systematic review and meta-analysis.

BACKGROUND: Post-stroke spasm is currently a complex clinical problem that remains to be resolved. Due to its excellent efficacy and few side effects, clinicians have used fire acupuncture to treat post-stroke spasticity in China. OBJECTIVES: The purpose of this study was to evaluate the clinical efficacy of fire acupuncture compared with conventional acupuncture to treat post-stroke spasms and provide a detailed summary of the commonly used acupoints. METHODS: Eight databases (MEDLINE/PubMed, Web of Science, the Cochrane database, EMBASE, CBM, CNKI, WanFang, and VIP) were searched for randomized controlled trials (RCTs) published from database inception through August 30, 2020. RCTs that compared fire acupuncture with conventional acupuncture as a treatment intervention for patients with spasticity after stroke were included. Revman 5.3 software was used to calculate risk ratios (RR) and standard mean differences (SMD) with 95% confidence intervals (CI). Methodological evaluation or critical appraisal of the included articles was assessed using RoB-2. RESULTS: Sixteen studies with a total of 1,118 patients were included. Although according to the standards of the Rob 2.0 tool, most studies are considered to have some problems. Comprehensive analysis of the results revealed a consistent trend indicating several advantages of using fire needles compared to conventional acupuncture in treating post-stroke spasms, including the effective rate, recovery rate, and improvement of multiple scales represented by MAS. Concerning secondary outcomes, using the scales of FMA, BI, or NDS in this random model meta-analysis, fire acupuncture exhibited better performance compared to acupuncture [SMD = 2.27, 95%CI [1.40,3.13 (random-effects model) ], [SMD = 1.46,95% CI [1.03,1.90 (random-effects model)], and [SMD = 0.90, 95%CI [0.44,1.35 (random-effects model)], respectively, with moderately high heterogeneity. When the effective rate was used as an outcome in the subgroup analysis, fire needles performed better than conventional acupuncture with respect to damage to the upper or lower limbs, and the thickness and depth of acupuncture. When the modified Ashworth scale (MAS) was used as the outcome, and the damage occurred in the lower extremity, the acupuncture depth exceeded 15mm, or the duration of stroke was longer than six months, the fire needles did not perform better than conventional acupuncture, [SMD = 0.01, 95%CI [-0.47,0.48 (fix-effects model)], [SMD = 0.21 [-0.51,0.93(random-effects model)], and [SMD = 0.76, 95%CI [-0.08,1.60 (random-effects model)], respectively. The acupoints identified with the highest frequencies in this study were Yang-meridian, including LI11-Quchi (nine times), LI4-Hegu (seven times), and ST36-Zusanli (five times). Moreover, no serious adverse effects were reported in any of the studies included in this analysis. CONCLUSIONS: Despite several limitations, this was the first meta-analysis to focus on the treatment of post-stroke spasticity using fire needle acupuncture compared with conventional acupuncture. Our results confirmed that fire needles could provide a better clinical effect than conventional acupuncture, which will help standardize fire needle treatment strategies for post-stroke spasms.

Related risk factors associated with post-stroke fatigue: a systematic review and meta-analysis.

BACKGROUND: Post-stroke fatigue (PSF) is one of the most common complications of stroke and has a negative impact on quality of life over time. Although several therapeutic approaches have been explored in the last decade, the risk factors responsible for the occurrence of PSF are still largely unknown. OBJECTIVE: The aim of this meta-analysis was to identify the risk factors contributing to PSF, especially clinical and social risk factors, which may help to prevent PSF. METHODS: A systematic literature search was performed with PubMed, EMBASE, Cochrane Library, and Web of Science databases from inception until April 2019. Only original studies measuring the association between potential risk factors and PSF were included. All relevant data the included studies were extracted by two independent reviewers using predefined data fields. RESULTS: Fourteen studies (n = 3933) were included in this meta-analysis. Female (OR = 1.39; p < 0.01), thalamus (OR = 1.76; p = 0.02), leucoaraiosis (OR = 1.73; p < 0.01), NIHSS score (OR = 1.16; p < 0.01), modified Rankin Scale (OR = 1.63; p < 0.01), depression (OR = 1.75; p < 0.01), and sleeping disturbances (OR = 2.01; p < 0.01) were all significantly associated with PSF. In the subgroup analysis, depression (OR = 2.75; p < 0.01) tended to be associated with Asian patients with PSF. For patients who had a stroke survive for more than half a year, PSF was more likely to occur in stroke survivors with depression (OR = 1.46; p < 0.01), anxiety (OR = 1.13; p < 0.01), or sleeping disturbances (OR = 1.98; p < 0.01). CONCLUSION: Despite some limitations, this study first identified that female and depression conferred an increased susceptibility to PSF, regardless of whether in European or Asian populations. Risk factors associated with PSF included female, thalamic, leucoaraiosis, depression, sleeping disturbances, diabetes mellitus, and anxiety. This meta-analysis shows that chronic PSF appears to be largely attributable to patients with multiple comorbidities. It is necessary to strengthen the treatment for stroke-related complications and improve stroke patient care, which could help to reduce the incidence of PSF. TRIAL REGISTRATION: CRD42019128751.

MiR-1260b promotes the migration and invasion in non-small cell lung cancer via targeting PTPRK.

OBJECTIVE: Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases which cause most of cancer-related deaths globally. As our previous study discovered miR-1260b can be regarded as a specific signature for metastasis in NSCLC patients. However, the molecular mechanisms of miR-1260b underlying NSCLC progression and metastasis remain dismal. METHODS: The expression of miR-1260b in NSCLC tissues and cell lines were examined by real-time PCR, the effects of miR-1260b on cell migration, invasion and proliferation were evaluated in vitro. Furthermore, luciferase reporter assay was performed to identify the targets of miR-1260b, and the association between miR-1260b and its target gene was determined by real-time PCR and western blot assay. RESULTS: The results showed that miR-1260b was significantly upregulated in NSCLC cell lines. The inhibition of miR-1260b expression decreased the migratory and invasive rates in A549 cells while miR-1260b overexpression had the opposite effect. Furthermore, PTPRK was identified as a direct target of miR-1260b, and PTPRK expression was inversely correlated with miR-1260b in NSCLC cell lines and clinical tissues. CONCLUSIONS: These results suggested that miR-1260b may play an important role in NSCLC metastasis progression and could serve as a putative target for diagnosis and treatment of NSCLC.

Bi deficiency-tuned functionality in multiferroic Bi1-δFe0.95Mn0.05O3 films.

Structural evolution and ferroelectric (FE)-to-antiferroelectric (AFE) transition behaviors were observed in Bi1-δFe0.95Mn0.05O3 (100)-textured films with a carefully controlled Bi deficiency concentration δ. Raman spectra revealed an orthorhombic structural transition induced by Mn substitution. The polarization-electric field hysteresis loops and capacitance-voltage loops of Bi1-δFe0.95Mn0.05O3 films clearly demonstrated antiferroelectric behavior with increasing δ. The responses of the domain structure of the Bi1-δFe0.95Mn0.05O3 film under positive and negative applied voltages directly suggested the coexistence of FE and AFE phases. The existence of (100) superstructure reflections and antiparallel displacements of the Bi atoms along the [100] direction observed by transmission electron microscopy unambiguously reveal the AFE phase. The chemical substitution-induced orthorhombic structural transition in BiFe0.95Mn0.05O3 film implies that as the δ concentration increases, the changes in Bi-O bonding and the stereochemical activity of Bi 6s lone pair affect both the ferroelectric distortion and the antiferrodistortive rotation and therefore drive the Bi1-δFe0.95Mn0.05O3 crystal lattice to form a PbZrO3-type orthorhombic phase with an AFE order. A continuing increase in Bi deficiency creates defect dipole complexes which produce an internal field leading to a preferred direction of the ferroelectric domain. The Bi deficiency in multiferroic BiFeO3 provides a new route by which to tune functionality.

Formation of conductive networks with both segregated and double-percolated characteristic in conductive polymer composites with balanced properties.

Morphological control of conductive networks involves the construction of segregated or double-percolated conductive networks is often reported to reduce the electrical percolation threshold of conductive polymer composites (CPCs) for better balance among electrical conductivity, mechanical properties, and filler content. Herein, the construction of conductive networks with both segregated and double-percolated characteristics is achieved based on polypropylene (PP)/polyethylene (PE) and multi-wall carbon nanotubes (CNTs). CNTs were firstly dispersed in PE; then PE/CNTs were compounded with PP particles well below the melting temperature of PP. It is observed that the percolation threshold (pc) decreases with increasing PP particle size (size 3.6 mm, pc=0.08 wt %), which agrees with previous theoretical prediction and experiment in much smaller particle size range. To further study this, the amount of CNTs in PE is varied. It is shown that the degree of PE/CNTs coating on PP particles varies with CNTs as well as PE content in these composites, and have significant influence on the final electrical property. Furthermore, a model combines classical percolation theory and model for segregated network has been proposed to analyze the effect of particle size, degree of coating and thickness of coating on the percolation behavior of these CPCs. In such a model the percolation of CNTs in PE phase as well as PENT phase in the segregated structure can be described. Overall, through such method, a much better balance among mechanical property, conductivity, and filler content is achieved in these CPCs comparing with the results in literature.

Fabrication of highly stretchable conductors via morphological control of carbon nanotube network.

Stretchable conductors, which can keep their excellent electrical conductivity while highly stretched, have been investigated extensively due to their wide range of applications in flexible and stretchable electronics, wearable displays, etc.; however, their preparation is often complicated and expensive. Herein, an efficient method to prepare high performance stretchable conductors through morphological control of conductive networks formed with carbon nanotubes (CNTs) in an elastomer matrix is reported. It is observed that an interface-mediated method could be used to align randomly oriented filler during stretching and to induce buckling of CNTs during relaxation. Further morphological studies indicate the possible formation of a wavy CNT structure induced by cyclic pre-straining. Subsequent thermal annealing is observed to collapse the oriented network and improve the local contacts between conductive networks. Through such a simple procedure, a conductivity of nearly 1000 S m(-1) and a stretchability of 200% can be achieved for composites containing 20 wt% CNTs. CNTs are observed to buckle over a large area in polymer bulk, and the combination of pre-straining and thermal annealing modifies the conductive network in the elastomer matrix. As a general method, this could be used for easy fabrication of high-performance stretchable conductors for arbitrary-shaped objects on a large scale.

Reactive oxygen species regulate Pseudomonas aeruginosa lipopolysaccharide-induced MUC5AC mucin expression via PKC-NADPH oxidase-ROS-TGF-alpha signaling pathways in human airway epithelial cells.

Mucin overproduction is a hallmark of chronic inflammatory airway diseases, such as asthma, chronic obstructive pulmonary disease, and cystic fibrosis. Excessive production of mucin leads to airway mucus obstruction and contributes to morbidity and mortality in these diseases. The molecular mechanisms underlying mucin overproduction, however, still remain largely unknown. Here, we report that the bacterium P. aeruginosa, an important human respiratory pathogen causing cystic fibrosis, utilizes reactive oxygen species (ROS) to up-regulate MUC5AC mucin expression. Pseudomonas aeruginosa lipopolysaccharide (PA-LPS) induces production of ROS through protein kinase C (PKC)-NADPH oxidase signaling pathway in human epithelial cells. Subsequently, ROS generation by PA-LPS releases transforming growth factor-alpha (TGF-alpha), which in turn, leads to up-regulate MUC5AC expression. These findings may bring new insights into the molecular pathogenesis of P. aeruginosa infections and lead to novel therapeutic intervention for inhibiting mucin overproduction in patients with P. aeruginosa infections.