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Background Immune dysfunction is one of the mechanisms to promote polycystic ovary syndrome (PCOS). Various immune cells have been reported to be involved in the development of PCOS. Meanwhile, the disturbance of metabolism is closely related to PCOS. The aim of this study is to explore the association of mucosal-associated invariant T (MAIT) cells and myeloid-derived suppressor cells (MDSCs) with the metabolic dysfunction in PCOS. Methods 68 PCOS patients and 40 controls were recruited in this study and we collected the peripheral blood of participants’ during their follicular phase. The frequencies of MAIT cells and MDSCs were determined by flow cytometry after being stained with different monoclonal antibodies. And the concentrations of cytokines were determined by ELISA. Results Compared to controls with normal metabolism, the frequency of MDSCs, CD8+MAIT cells and CD38+CD8+MAIT cells were significantly decreased in PCOS patients with normal metabolism, however, proportion of CD4+MAIT cells exhibited a noticeable increase. Similar results of CD8+MAIT, CD38+CD8+MAIT cells and reduced expression of IL-17 were observed in PCOS patients with metabolic dysfunction as compared to controls with metabolic disorders. PCOS patients with excessive testosterone levels displayed significantly decreased levels of CD8+MAIT, CD38+CD8+MAIT cells, MDSCs and Mo-MDSCs as compared to PCOS patients with normal testosterone concentrations. PCOS patients with abnormal weight showed a lower level and activation of CD8+MAIT cells. On the contrary, they displayed an enrichment of CD4+MAIT cells. PCOS patients with glucose metabolic disorder displayed a remarkable dysregulation of MDSCs and Mo-MDSCs. MDSCs were positively correlated with MAIT cells. Negative correlations between the frequency of CD8+MAIT cells, CD38+CD8+MAIT cells and body mass index were revealed. CD4+MAIT cells positively correlated with BMI. Mo-MDSCs were found to be negatively related to the levels of 2hour plasma glucose and HOMA-IR index. Conclusion The impairment of CD8+MAIT cells and MDSCs is involved in the metabolic dysfunction of PCOS.

Skin is the largest organ of the human body. Skin wound is one of the most common forms of wound. Mesenchymal stromal cells (MSCs) have been used to aid skin wound healing via their paracrine factors. Because the secretome of MSCs can be greatly enriched and amplified by treatment with IFN‐γ and TNF‐α (IT), we here tested whether supernatant derived from MSCs pretreated with IT, designated as S‐MSCs‐IT, possesses improved wound healing effect by using a murine model of cutaneous excision, S‐MSCs‐IT was found to be more potent in promoting angiogenesis, constricting collagen deposition and accelerating wound closure than control supernatant (S‐MSCs) during the healing of skin wound. VEGFC, but not VEGFA, was greatly upregulated by IT and was found to be a key factor in mediating the improved wound healing effect of S‐MSCs‐IT. Our results indicate that the beneficial paracrine effect of MSCs on wound healing can be enhanced by pretreatment with inflammatory cytokines. IT treatment may represent a new strategy for optimizing the therapeutic effect of MSCs on skin injuries., TNF‐α and IFN‐γ stimulation upregulates the expression of VEGFC in mesenchymal stromal cells, which acts on endothelial cells and promotes angiogenesis, thus accelerating skin wound healing.

Background This study aims to explore the predictive factors of central lymph node metastasis (CLNM) in patients with papillary thyroid microcarcinoma (PTMC) without capsule invasion. Methods From January 2016 to October 2018, 1,622 patients with PTMC, who underwent surgical treatment at Zhejiang Cancer Hospital, were enrolled in the present study. A model of multivariate logistic regression was developed to find the variables that were independently associated with CLNM. The results were presented in the odds ratio (OR) with a 95% confidence interval (CI). The nomogram for predicting CLNM was developed based on the results of the multivariate logistic regression analysis. The distance (distance >0) from tumor to capsule is defined as the shortest distance from the tumor boundary to the capsule or trachea. Results The multivariate logistic regression analysis indicated that age, gender, tumor maximum diameter, tumor mean diameter, and tumor volume were independently associated with CLNM. In the 692 cases without capsular invasion, the distance from the capsule was not correlated to the CLNM. The joint model, which included age, gender, tumor volume, and capsular invasion, were analyzed using the ROC curve. The cut-off point for the prediction of CLNM was defined as a value of 0.208. The area under the ROC curve was 0.687, the sensitivity was 65.4%, and the specificity was 63.3%. Conclusions Gender, age, maximum diameter, mean diameter, tumor volume, and capsular invasion were independently associated with the CLNM. When there was no capsular invasion, the distance between the tumor and capsule was not correlated to the CLNM, suggesting that considering whether the tumor is close to the capsule may not be necessary for low-risk PTMC.

Annular epidermolytic ichthyosis (AEI) is a rare autosomal dominant ichthyosis that was recently described in 10 separate families in the English literature. There are no reports on the phenotypic heterogeneity of AEI. We investigated, for the first time, a large Chinese AEI pedigree exhibiting interfamilial phenotypic heterogeneity. We collected clinical data and DNA from the members of the family, and skin lesions were obtained from two patients with different phenotypes. Skin imaging examinations were performed. Whole-exome sequencing (WES) and Sanger sequencing were used to detect gene mutations. The characteristic features of granular layer degeneration in the two biopsies were verified via histological methods. The missense mutation c.1436T > Cin KRT1 was detected in all nine patients. This study demonstrates that AEI may present with different clinical phenotypes and that mutation analysis for suspected cases is necessary to obtain a precise diagnosis.

Despite a strong evidence on the negative association between HIV-related stigma and quality of life (QoL), few studies have examined the indirect effects of this relationship. This study aimed to examine the association between HIV-related stigma and QoL and the indirect effects of positive coping and perceived stress in people living with HIV and depressive symptoms (PLWHD). This study used baseline date from a randomized controlled trial. Structural equation model was used to examine the association between HIV-related stigma and QoL as well as the indirect effects of positive coping and perceived stress. Perceived and internalized stigma had negative direct (

Background Lipid peroxidation yields a large number of aldehydes and carbonyl-containing compounds, of which the reactive and toxic compound 4-hydroxy-2-nonenal (4-HNE) derived from ω-6 polyunsaturated fatty acids (ω-6 PUFAs) is the most extensively studied. The high reactivity of 4-HNE enables this compound to crosslink with various biomolecules and thus contribute to the pathological processes of several diseases, such as atherosclerosis, cancer, diabetes mellitus, and neurodegenerative disorders. Scope and approach From the perspective of food safety, the emergence of lipid peroxidation contaminants in foodstuffs remains a major concern of consumers, health departments, and industries. This review highlights the latest developments regarding the formation pathways, toxicity, analysis methods, occurrence in foodstuff, and mitigation strategies for 4-HNE. Future prospects on measuring and controlling 4-HNE in food are also discussed. Key findings and conclusions The determination of 4-HNE levels in different types of foods indicates that PUFAs-rich vegetable oil and oil-based food are major intake sources of 4-HNE. Considering the toxicity of 4-HNE, sensitive detection techniques combined with feasible control methods should be an effective solution for food quality maintenance and safety assurance. However, current detection methods and 4-HNE control strategies possess inherent advantages and limitations. Therefore, effective 4-HNE detection and new controlling technologies that are practically viable at the industrial level need to be developed.

A stretchable, 3D tubular structure formed due to processing-induced wrinkles is proposed as a platform to develop adaptive stretchable electronics. This integrated structure is fabricated by releasing a pre-stretched 2D film-substrate precursor, resulting in a wrinkled surface, that shows a strong directional dependence that drives the tube formation. This 3D shape adaptivity can control the radial opening and closing of the tube through longitudinal strain, which inspires the development of a dual-channel piezoresistive strain sensor/switch concomitant with mechanochromic effect and an intriguing tactile responsive artificial Mimosa pudica device. In addition, the system is compatible with 2D film deposition technologies, which allows customized electrode patterns to be coated on the pre-stretched 2D precursor followed by wrapped inside as precursor released. Upon sealing the tube, this “coating and self-wrapping” feature allows for the invention of a highly stretchable tactile switch, and a stretchable tubular supercapacitor with dual stimuli-responsiveness.

Background To distinguish acute progressive ischemic stroke (APIS) from acute non-progressive ischemic stroke (ANPIS) is clinically critical for the precise treatment and prevention of acute ischemic stroke (AIS) deterioration. Serum proteins could reflect the unique pathophysiological processes of APIS. It is expected to find serum protein biomarkers to identify APIS at the early state, especially when typical symptoms have not been present in conventional clinical indices. Methods We recruited 178 subjects, including 133 AIS patients and 45 healthy controls. The discovery set, which included 10 age- and sex- matched cases from each of the APIS, ANPIS and control groups, was used for serum proteomic analysis with a mass spectrometry-based proteomics. The disrupted proteins of APIS were screened, of which, those common to ANPIS and specific to APIS were particularly concerned. Potential biomarkers of APIS were screened based on the theoretical knowledge to explain the mechanism and diagnostic value, and subsequently tested in the validated set (25 APIS patients, 88 ANPIS patients, and 35 controls). Results We found that 46 serum proteins were disturbed in the APIS patients; 23 differentially expressed proteins (DEPs) were common to these two groups, and 23 DEPs were associated with APIS alone. Enrichment analysis suggested that complement activation, cytolysis, proteolysis, positive regulation of fibrinolysis, blood coagulation were specifically associated with APIS; while inflammatory response, neutrophil chemotaxis, oxygen transport, and positive regulation of cell death process were common to AIPS and ANPIS. Serum amyloid A1 (SAA1) and S100 calcium binding protein A9 (S100-A9) jointly conferred a moderate value (AUC = 0.799) to diagnose APIS and to distinguish APIS from ANPIS (AUC = 0.699). Conclusions This study provides human serum proteomic evidence that inflammation, oxidative stress, and necrosis in APIS are common to ANPIS; the progressive feature of APIS may be mainly associated with complement activation, more serious inflammation, and lipid metabolic disorder; SAA1 and S100-A9 may be considered as potential biomarker panel of APIS.

On basis of vibration images and transfer learning, this work presents a method for fault diagnosis of rotating machinery. Vibration images can be regarded as a combination of several traditional single-point sensors, which provide abundant full-field vibration information. The frequency-domain features of vibration acceleration are extracted according to the motion phase in images. Then proposed method utilizes a transfer learning method, called joint distribution adaptation, to construct a shared feature space. In this space, the marginal probability distribution and conditional distribution of vibration signals in two different conditions are minimized. Afterwards, the k-Nearest Neighbor classifier is used in this space for fault diagnosis. Experimental results manifest the proposed method can effectively diagnose faults under different working conditions and between different machineries, and the diagnosis accuracy is above 90%.

In this paper, a three-dimensional axis orbit reconstruction method based on machine vision is proposed for rotating machinery. Firstly, the center of rotor is marked and its motion is videotaped. Secondly, the local phase of captured image sequences is extracted, which is linear with the axis orbit displacement. Combined with the binocular stereo vision, three-dimensional axis orbit is reconstructed. According to the linear relation between phase and displacement, the actual axis orbit can be obtained. Finally, the experiment is performed on a permanent magnet synchronous motor, and the experimental results verify the effectiveness of the proposed method.

Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6-deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet-deficient mice or in nude mice adoptively transferred with T-bet-deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs., The formation of the pre-metastatic niche enables the colonisation of disseminated cancer cells in distant organs. Here, the authors show that Th2 cytokines induce Complement 3 production in lung mesenchymal stromal cells, which recruits neutrophils and promotes the formation neutrophil extracellular traps, facilitating breast cancer cell metastasis to the lungs.

Background Post-esophagectomy patients often experience a clinically relevant deterioration of quality of life after esophagectomy due to malnutrition, impaired exercise capacity, and psychological problems. The widespread use of mobile health (mHealth) has been increasingly promising for interdisciplinary healthcare givers to deliver efficient and potential cost-effective interventions in cancer patients. However, comprehensive interventions delivered by mHealth with a rigorous design of randomized controlled trial in post-esophagectomy patients were scarce. Methods This study developed the first comprehensive intervention model by mHealth with a parallel RCT design, providing nutrition, physical exercise, and psychological support for post-esophagectomy patients. A total of 120 patients will be randomized into the intervention group or the control group receiving treatment as usual. Participants in the intervention group will receive the 3-month intervention of the CIMmH program via the enhanced WeChat platform and by specialists (offline). The online program includes nutrition guidelines, physical exercise instructions, and psychological courses. All participants will be assessed at baseline, 1, and 3 months after esophagectomy. The primary outcomes are health-related QOL, weight, and physical fitness measured by 6-minute walking distance. Secondary outcomes include nutritional biomarkers, body composition, strength, interleukin-6, depressive symptoms, anxiety, and coping. Discussion This study is among the first efforts to innovatively develop a comprehensive intervention program to prompt rehabilitation in post-esophagectomy patients. Once proven effective, CIMmH could be integrated into the management of post-esophagectomy patients. Key messages Esophageal cancer, QOL, Nutrition, Physical exercise, Psychological support, mHealth

We aimed to assess the difference in the accuracy of readings from automated office blood pressure machines with each other or with manual office blood pressure measurements in Chinese individuals. We collected awake 48-h ambulatory blood pressure monitoring, two automated office blood pressure device (BpTRU and WatchBP) readings, and manual office blood pressure measurements in Chinese patients (n = 135) with hypertension in a randomized sequence. Differences were compared using paired t-tests and Bland–Altman plots. The sensitivity and specificity of the techniques for detecting elevated blood pressure were calculated using awake ambulatory blood pressure monitoring as the reference standard. The WatchBP device’s and awake ambulatory blood pressure readings were similar. The BpTRU device provided significantly lower mean systolic (P

Background Patients with esophageal cancer often experience clinically relevant deterioration of quality of life (QOL) after esophagectomy owing to malnutrition, lack of physical exercise, and psychological symptoms. Objective This study aimed to evaluate the feasibility, safety, and efficacy of a comprehensive intervention model using a mobile health system (CIMmH) in patients with esophageal cancer after esophagectomy. Methods Twenty patients with esophageal cancer undergoing the modified McKeown surgical procedure were invited to join the CIMmH program with both online and offline components for 12 weeks. The participants were assessed before surgery and again at 1 and 3 months after esophagectomy. QOL, depressive symptoms, anxiety, stress, nutrition, and physical fitness were measured. Results Of the 20 patients, 16 (80%) completed the program. One month after esophagectomy, patients showed significant deterioration in overall QOL (P=.02), eating (P=.005), reflux (P=.04), and trouble with talking (P Conclusions The CIMmH was feasible and safe and demonstrated encouraging efficacy testing with a control group for enhancing recovery after surgery among patients with esophageal cancer in China. Trial Registration Chinese Clinical Trial Registry (ChiCTR-IPR-1800019900); http://www.chictr.org.cn/showprojen.aspx?proj=32811.

One of the most common promoters of the initiation and growth of the tumor is an immune disturbance. Numerous immune cells and inflammatory factors play a role in the tumor-immune microenvironment. However, few studies have investigated the correlation between these immunological events and clinical consequences in cervical cancer. We measured the levels of numerous inflammatory mediators and frequencies of regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and mucosal-associated invariant T (MAIT) cells in peripheral blood (PB) of cervical cancer patients. Cervical cancer patients showed elevated production of interleukin (IL)-18 and plasma C-C chemokine ligand (CCL) 3/5. Meanwhile, an accumulation of C-C chemokine receptor 5 (CCR5) monocytic (Mo)-MDSCs and Tregs was observed. The cervical cancer group displayed increased frequencies of CD8+ , CD4+ and highly activated CD38+ CD8+ MAIT cells, and reduction of double-negative (DN) and PD1(CD279+ ) DN MAIT cells. Importantly, it was demonstrated that MAIT cells were positively related to Mo-MDSCs. Furthermore, an elevated concentration of PD1(CD279+ ) DN MAIT cells was significantly related to increased progression-free survival of patients with cervical cancer. In conclusion, our study suggests that the combined action of Mo-MDSCs and MAIT cells might be associated with the progression of cervical cancer, and the frequency of DN MAIT cells in the peripheral blood mononuclear cells was associated with the survival benefit of patients.

Background Traditional Chinese medicine (TCM) may improve the prognosis management of cholelithiasis patients after gallbladder-preserving lithotripsy. To explore the evidence for this view, we systematically reviewed the efficacy and safety of TCM for improving the prognosis of cholelithiasis after gallbladder-preserving lithotripsy and performed functional pathway enrichment analysis of TCM target genes. Methods In this systematic review (SRs), we searched six Chinese or international databases to collect randomized controlled clinical trials (RCTs) of TCM in preventing the recurrence of cholelithiasis after gallbladder-preserving lithotripsy. The literature was independently screened by 2 reviewers, who then extracted the data. The Cochrane risk-of-bias and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tools were used to assess the included studies' risk of bias and quality of evidence, respectively. And, the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses would be conducted on the TCM prescriptions in the included literature to find the effective component and mechanism of TCM in the prognosis management of gallbladderpreserving lithotripsy. Analysis in this research would be conducted by R 3.5.2 software. Results A total of 1,024 articles were retrieved, and 9 RCTs involving 926 participants were included after the step-by-step screening. The risk of bias for each important outcome in all the studies was "uncertain". The meta-analysis showed that compared with blank control, TCM prevented cholelithiasis by decreasing the recurrence rate, complications incidence, gallbladder wall thickness, and gallbladder contraction degree. But, there were no significant differences in the rate of the adverse reaction. The result of the GO and KEGG analysis revealed that the mechanism of prevention of TCM in gallstone recurrence may be related to the cholesterol metabolic pathway and that naringin from Glycyrrhiza may be the effective component in the prevention of recurrence. Conclusions Existing evidence suggests that the use of TCM may reduce the recurrence rate after gallbladder-preserving lithotripsy and this effect may be related to the flavonoid glycoside naringin from Glycyrrhiza uralensis, but more RCTs with high quality in this area may be needed to have a robust conclusion.

People living with HIV (PLWH) suffer from high rates of mental illness; but targeted effective interventions are limited, especially in developing countries. High penetration of smartphone usage and widespread acceptance of social media applications provide an unprecedented opportunity for mobile-based health interventions (mHealth interventions) in resource-limited settings like China. The current report describes the design and sample characteristics of the Run4Love randomized controlled trial (RCT) aimed at improving mental health in PLWH in China. A total of 300 PLWH with elevated depressive symptoms were recruited and randomized into either the intervention or control group. Participants in the intervention group received an adapted cognitive-behavioral stress management (CBSM) course delivered by the enhanced WeChat platform (for 3 months) and were motivated to engage in physical activities. Progress of the participants was automatically tracked and monitored with timely feedback and rewards. The control group received a brochure on nutrition for PLWH in addition to standard care. The outcome assessments are conducted at baseline, 3, 6, and 9 months using tablets. The primary outcome is depressive symptoms measured by the scale of the Center for Epidemiology Studies Depression (CES-D). Secondary outcomes include quality of life, chronic stress measured with biomarker of hair cortisol, and other measures of stress and depression, self-efficacy, coping, HIV-related stigma, physical activity, and patient satisfaction. Mixed effects model with repeated measures (MMRM) will be used to analyze the intervention effects. The Run4Love study is among the first efforts to develop and evaluate a multicomponent and integrated mHealth intervention to improve the mental health and quality of life of PLWH. Once proven effective, Run4Love could be scaled up and potentially integrated into the routine case management of PLWH and adapted to other populations with chronic diseases. Chinese Clinical Trial Registry - ChiCTR-IPR-17012606 , registered on 07 September 2017.

Background Mobile health (mHealth) interventions have been shown to effectively improve the quality of life (QOL) among people living with HIV. However, little is known about the long-term effects of mHealth interventions. Objective This study aims to explore the intervention mechanisms of a social media–based intervention, Run4Love, on the QOL of people with HIV over across a 9-month follow-up period. Methods We recruited people living with HIV who were concurrently experiencing elevated depressive symptoms from an HIV outpatient clinic in South China. A total of 300 eligible participants were randomized either to the intervention group or the control group in a 1:1 ratio after they provided informed consent and completed a baseline survey. The intervention group received a 3-month WeChat-based intervention, comprising cognitive-behavioral stress management (CBSM) courses and physical activity promotion. The control group received a printed brochure on nutrition guidelines in addition to the usual care for HIV treatment. Neither participants nor the research staff were blinded to group assignment. All patients were followed at 3, 6, and 9 months. The primary outcome was depressive symptoms. Structural equation model (SEM) with longitudinal data was conducted to examine the sequential mediating effects of HIV-related stigma and depressive symptoms on the long-term intervention effects on participants’ QOL. Results About 91.3% (274/300), 88.3% (265/300), and 86.7% (260/300) of all participants completed follow-up surveys at 3, 6, and 9 months, respectively. Results showed that the intervention had significantly improved participants' QOL at 9 months, via complete mediating effects of reduced HIV-related stigma at 3 months and decreased depressive symptoms at 6 months. No adverse events were reported. Conclusions These findings underscore the critical roles of HIV-related stigma and depressive symptoms in an mHealth intervention with long-term effects on QOL improvements. We call for targeted mHealth interventions to improve QOL among people living with HIV, especially social media–based interventions that can address HIV-related stigma and alleviate depressive symptoms. Trial Registration Chinese Clinical Trial Registry ChiCTR-IPR-17012606; https://www.chictr.org.cn/showproj.aspx?proj=21019

Background Although several studies have investigated the effects of mobile health (mHealth) interventions on depression among people living with HIV, few studies have explored mediators of mHealth-based interventions to improve mental health in people living with HIV. Identifying influential mediators may enhance and refine effective components of mHealth interventions to improve mental health of people living with HIV. Objective This study aimed to examine mediating factors of the effects of a mHealth intervention, Run4Love, designed to reduce depression among people living with HIV using 4 time-point measurement data. Methods This study used data from a randomized controlled trial of a mHealth intervention among people living with HIV with elevated depressive symptoms in Guangzhou, China. A total of 300 patients were assigned to receive either the mHealth intervention (n=150) or a waitlist control group (n=150) through computer-generated block randomization. Depressive symptoms, coping, and HIV-related stigma were measured at baseline, 3-, 6-, and 9-month follow-ups. The latent growth curve model was used to examine the effects of the intervention on depressive symptoms via potential mediators. Mediating effects were estimated using bias-corrected 95% bootstrapped CIs (BCIs) with resampling of 5000. Results Enhanced positive coping and reduced HIV-related stigma served as effective treatment mediators in the mHealth intervention. Specially, there was a significant indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of positive coping (beta=–2.86; 95% BCI –4.78 to –0.94). The indirect effect of the mHealth intervention on the slope of depressive symptoms via the slope of HIV-related stigma was also statistically significant (beta=–1.71; 95% BCI –3.03 to –0.40). These findings indicated that enhancement of positive coping and reduction of HIV-related stigma were important mediating factors of the mHealth intervention in reducing depression among people living with HIV. Conclusions This study revealed the underlying mediators of a mHealth intervention to reduce depression among people living with HIV using latent growth curve model and 4 time-point longitudinal measurement data. The study results underscored the importance of improving positive coping skills and mitigating HIV-related stigma in mHealth interventions to reduce depression among people living with HIV.

Background People living with HIV and depression have high rates of suicide. Studies of mobile health (mHealth) interventions have shown feasibility, acceptability, and efficacy in improving mental health in people living with HIV and depression. However, few studies have examined the mechanisms and effects of mHealth interventions on suicide. Objective This study was designed to examine the mechanisms and effects of a WeChat-based intervention, Run4Love, on suicide among people living with HIV and depression in China, while considering perceived stress and depressive symptoms as mediators. Methods A sample of 300 People living with HIV and depression was recruited from the outpatient clinic of a large HIV or AIDS treatment hospital and was randomized to the Run4Love group or a control group. Data were collected at baseline, 3-, 6-, and 9-month follow-ups. Path analysis modeling, with longitudinal data, was used in data analyses. Results The Run4Love mHealth intervention had a direct effect on reducing suicide rate at the 6-month follow-up (beta=−.18, P=.02) and indirect effect through reducing perceived stress and depressive symptoms at the 3-month follow-up (beta=−.09, P=.001). A partial mediating effect between perceived stress and depressive symptoms accounted for 33% (–0.09/–0.27) of the total effect. Conclusions Through path analyses, we understood the mechanisms and effects of an mHealth intervention on suicide prevention. The findings underscored the importance of stress reduction and depression treatment in such a program. We call for more effective suicide prevention, especially mHealth interventions targeting the vulnerable population of people living with HIV and depression. Trial Registration Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showprojen.aspx?proj=21019

Background: Studies have reported that myeloid-derived suppressor cells (MDSCs) contribute to maintain pregnancy. The aim of this case-control study was to test whether there is a dysregulation of peripheral MDSCs in recurrent implantation failure (RIF).Methods: 26 RIF patients and 30 controls were recruited. Flow cytometry was applied to characterize polymorphonuclear (PMN)-MDSCs, monocytic-MDSCs (M-MDSCs), effector T cells (Teffs) and regulatory T cells (Tregs) in blood. ELISA was used to define MDSCs correlative cytokines and chemokines in serum from all patients.Results: Compared with controls, RIF patients showed significant reductions of blood PMN-MDSCs, M-MDSCs, Tregs and NO production by PMN-MDSCs, whereas the expression of ζ chain on CD4+T cell receptor (TCR) and CD8+TCR displayed a remarkable upregulation in RIF patients. Moreover, RIF patients presented a lower concentration of serum chemokine (C-C motif) ligand (CCL) 5 and transforming growth factor (TGF)-β than those from controls. Furthermore, the level of TCR ζ chain on CD4+ and CD8+ Teffs was negatively correlated not only with the percentage of PMN-MDSCs, but also with the amount of NO produced by PMN-MDSCs. The frequency of PMN-MDSCs had positive correlations with the concentration of CCL5 and TGF-β.Conclusions: This study indicated that the dysregulation of MDSCs might impair maternal-fetal immune balance thus resulting in RIF.

Background People undergoing mass home- and community-based quarantine are vulnerable to mental health disorders during outbreaks of coronavirus disease (COVID-19), but few studies have evaluated the associated psychosocial factors. Objective This study aimed to estimate the prevalence of anxiety and depressive symptoms and identify associated demographic and psychosocial factors in the general Chinese population during the COVID-19 pandemic quarantine period. Methods Participants aged 18 years or above were recruited in a cross-sectional online survey using snowball sampling from February 26-29, 2020. The survey included questions on demographics, family relationships, chronic diseases, quarantine conditions, lifestyle, COVID-19 infection, and anxiety and depressive symptoms. Logistic regression analyses were conducted to identify factors associated with elevated anxiety or depressive symptoms. Results Out of 2331 participants, 762 (32.7%) experienced elevated anxiety or depressive symptoms. Nine risk factors associated with anxiety or depressive symptoms included younger age, reduced income, having cancer or other chronic diseases, having family members living with cancer, concerns related to COVID-19 infection for themselves or family members, living alone, having family conflicts, having 8 hours of sedentary time per day, and worsened sleep quality. Conclusions The findings highlight an urgent need for psychological support for populations at high risk for elevated anxiety or depressive symptoms during the COVID-19 pandemic.

Background People living with HIV (PLWH) have high rates of depressive symptoms. However, only a few effective mental health interventions exist for this vulnerable population. Objective The aim of this study was to assess the efficacy of a WeChat-based intervention, Run4Love, with a randomized controlled trial among 300 people living with HIV and depression (PLWHD) in China. Methods We recruited PLWH from the HIV outpatient clinic in South China. Participants were screened based on the Center for Epidemiologic Studies-Depression (CES-D) scale. Those who scored 16 or higher were eligible to participate. A total of 300 eligible patients were enrolled. After obtaining informed consent from the participants, completion of a baseline survey, and collection of participants’ hair samples for measuring cortisol, the participants were randomly assigned to an intervention or a control group in a 1:1 ratio. The intervention group received the Run4Love program, delivered via the popular social media app WeChat. Cognitive behavioral stress management courses and weekly reminders of exercise were delivered in a multimedia format. Participants’ progress was monitored with timely and tailored feedback. The control group received usual care and a brochure on nutrition for PLWH. Data were collected at 3, 6, and 9 months. The primary outcome was depression, which was measured by a validated instrument. Results Participants in the intervention and control groups were comparable at baseline; about 91.3% (139/150), 88.3% (132/150), and 86.7% (130/150) participants completed the 3-, 6-, and 9-month follow-ups, respectively. At the 3-month follow-up, a significant reduction in CES-D score was observed in the intervention group (from 23.9 to 17.7 vs from 24.3 to 23.8; mean difference=−5.77, 95% CI −7.82 to −3.71; P Conclusions The WeChat-based mobile health (mHealth) intervention Run4Love significantly reduced depressive symptoms among PLWHD, and the effect was sustained. An app-based mHealth intervention could provide a feasible therapeutic option for many PLWHD in resource-limited settings. Further research is needed to assess generalizability and cost-effectiveness of this intervention. Trial Registration Chinese Clinical Trial Registry ChiCTR-IPR-17012606; http://www.chictr.org.cn/showproj.aspx?proj=21019 (Archived by WebCite at https://www.webcitation.org/78Bw2vouF)

We herein report the first attempt to engineer a coaxial-sensing 3D amplifier able to achieve dynamic self-assembly in response to a mutated-ctDNA target. A bio-nanofiber is firstly manufactured via an ingenious double-channel electrostatic spinning and DNA rolling circle replication (RCR) technology, which offered an ideal scaffold for assembly of 3D amplifier activated by target recognition. The coaxial-controllable signal amplifier presented several advantages. (1) Given its "coaxial sensing effect", the proposed bio-amplifier played the coaxial transduction for signal enrichment to vastly increase sensitivity, capable of discriminating a single-base mismatched sequence from the perfectly complementary one, using ctDNA-134A as a model analyte. (2) Due to "covalent bridges lock effect" in an identifying chip with locked nucleic acid beacons, this 3D amplifier expressed high specificity and biostability toward seven different mutated-ctDNAs. (3) Profiting from special configuration of bioactive nanofibers and DNA replication programming, this catalytic bio-amplifier possessed "signal enrichment effect", which enhanced dynamic range toward ctDNA-134A detection and hybridized without any external indicators. This innovative bio-amplifier has a detection limit of 5.1 aM for ctDNA-134A with superior specificity, excellent sensitivity, and good performance. This pioneered method was further applied for broadly differentiate cells and evaluate changes in the expression levels of intracellular mutated-ctDNAs.

Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the proprotein convertase family. It is an important regulator of cholesterol metabolism. PCSK9 can bind to low-density lipoprotein receptors (LDLRs) and induce the degradation of these receptors through the endosome/lysosome pathway, thus decreasing the LDLR levels on the cell surface of hepatocytes, resulting in increased serum low-density lipoprotein cholesterol (LDL-C) concentrations. Recent studies have found that gene polymorphisms of PCSK9 are associated with hypercholesterolemia, risk of atherosclerosis, and ischemic stroke. Furthermore, monoclonal antibodies, peptide mimetics, small molecule inhibitors and gene silencing agents that are associated with PCSK9 are some of the newer pharmaceutical therapeutic strategies and approaches for lowering serum LDL-C levels. In this review, we will discuss recent advances in PCSK9 research, which show that PCSK9 is correlated with lipid metabolism, atherosclerosis, and, in particular, ischemic stroke. We will also discuss the current state of PCSK9 therapeutics and their potential in modulating these diseases.