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Alveolar echinococcosis (AE) may affect the composition of the host's gut microbiota, potentially disrupting the balance between the gut microbiota and metabolites. Metagenomics and untargeted metabolomics were employed to characterize changes in the gut microbiota and metabolites in mouse models infected with E. multilocularis. Pearson correlation coefficients were calculated to compare the distribution of microbiota and metabolites, revealing synergistic or mutually exclusive relationships. Functional outputs of the gut microbiota were explored using the CAZy database and six enzymes involved in carbohydrate metabolism were identified with statistically significant differential expression between infected and control groups. The resistome was characterized by identifying antibiotic resistance genes annotated in the Comprehensive Antibiotic Resistance Database from the metagenomes of the groups. Firmicutes are the main carrier of ARGs in the host gut with tetQ being most prevalent. Antibiotic efflux, inactivation and target modification were the principal mechanisms of resistance. Comparison and analysis of two sets of antibiotic metabolic pathways allowed the identification of enzyme reactions unique to infected mice. KEGG pathway overview shows phenazine biosynthesis involving phzG to be one of them. In conclusion, infection with AE in mice leads to an overall disruption of gut microbiota and metabolites with the involvement of enzymes related to carbohydrate metabolism. Furthermore, antibiotic-resistance genes may play a role in disease progression, offering potential insights into the relationship between antibiotic use in AE and treatment outcomes.

Abstract Background Low-level viremia (LLV) has been identified as a potential precursor to virologic failure (VF), yet its clinical implications, particularly within the context of Integrase Strand Transfer Inhibitors (INSTIs)-based regimens, remain insufficiently explored. The study aimed to investigate the relationship between LLV and VF within ART-naïve patients on INSTIs-based regimens in China. Methods A longitudinal cohort study was conducted with ART-naïve patients aged ≥ 18 years at Beijing Ditan Hospital, under the Chinese National Free Antiretroviral Treatment Program (NFATP). The LLV was defined as a viral load (VL) ranging from 50 to 199 copies/mL after six months of ART initiation, and VF as a VL ≥ 200 copies/mL. Sensitive analyses were also performed, defining LLV as 50–999 copies/mL and VF as exceeding 1000 copies/mL. Multivariate logistic regression, Kaplan-Meier (KM) curve, and Generalized Estimating Equation (GEE) models were used to evaluate the risk factors associated with LLV and VF events. Results The study involved 830 ART-naïve patients, comprising 600 in the INSTIs group and 230 in the protease inhibitors (PIs) group. LLV events were observed in 10.4% of patients on PIs-based regimens and and 3.2% on INSTIs-based regimens (P

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries with pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, but timely diagnosis is challenging due to the non-specific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions is important for radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis.

Abstract Background The COVID‐19 pandemic has created challenges with respect to HIV care services. Remote online services might provide an effective method for health service delivery to people living with HIV (PLHIV). Few studies have focused on the efficacy of telemedical services for PLHIV and the effect of antiretroviral treatment via online services in China. Methods We developed a platform called the “No. 8 Health” for online antiretroviral drug collection and delivery services in Beijing from January 21 to June 30, 2022. We evaluated the online treatment service according to viral load suppression rates and compared differences in social characteristics between PLHIV who received antiretroviral drugs through online or offline treatment services. Results By June 2022, 9528 PLHIV had received outpatient treatment services, among which 44.6% (4031/9528) used the online treatment and drug delivery services for a total of 5590 person‐times. The satisfaction rate was 100%. Rates of viral load suppression among PLHIV who initiated antiretroviral therapy (ART) in 2020 and 2021 were 96.4% and 93.1%, respectively. Results showed that the viral load suppression rate was 97.9%. Regarding HIV rapid self‐testing, 4513 men who have sex with men used the online HIV rapid testing service. The number of users was approximately the same as in 2021, but both were slightly lower than those in 2020. Conclusion This study was the first to evaluate the effect of online drug collection and delivery services and virologic outcomes among PLHIV in China. The online service helped with maintenance of ART services, but the COVID‐19 pandemic still had some impacts on viral load suppression.

Abstract Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier’s endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

BackgroundAntiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children.MethodsFrom January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2–4 adverse events and abnormal laboratory test results.ResultsA total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5–10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3–4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5–6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p 5 days of LPV intake (aHR = 1.889, 1.004–3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299–5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238–0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2–4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children.ConclusionOur research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

The potential distribution range and management strategies for P. viburni are poorly understood. Based on historical distribution data and environmental factors, the present study predicted the potentially suitable areas for P. viburni spread under different climate change scenarios using MaxEnt (maximum entropy). The results showed that precipitation of the coldest quarter (Bio19), precipitation seasonality (Bio15), and mean temperature of the wettest quarter (Bio8) were the most important environmental factors determining the distribution of P. viburni. Under the current climate conditions, its potential suitable areas are southern China, the whole of Japan, North America (especially the eastern part of the United States), the southwestern part of South America, the Mediterranean coast and most of Europe, the central part of Africa, i.e., the south of the Sahara Desert, and most of the southern coast of Australia. The total area of habitats suitable for this insect pest is predicted to be increased in the future. In order to prevent P. viburni transmission and spread, there is a need to strengthen the monitoring and quarantine measures against this pest at the Southern ports.

The clinical outcomes of cancer nanovaccine have been largely impeded owing to the low antigen-specific T cell response rate and acquired resistance caused by the immunosuppressive tumor microenvironment (TME). Here, we reported a tumor acidity-responsive nanovaccine to remodel the immunosuppressive TME and expand the recruitment of tumor infiltrating lymphocytes (TILs) using hybrid micelles (HM), which encapsulated colony stimulating factor 1 receptor (CSF1-R) inhibitor BLZ-945 and indoleamine 2,3-dioxygenase (IDO) inhibitor NLG-919 in its core and displayed a model antigen ovalbumin (OVA) on its surface (denoted as BN@HM-OVA). The bioactive nanovaccine is coated with a polyethylene glycol (PEG) shell for extending nanoparticle circulation. The shell can be shed in response to the weakly acidic tumor microenvironment. The decrease in size and the increase in positive charge may cause the deep tumor penetration of drugs. We demonstrated that the bioactive nanovaccine dramatically enhance antigen presentation by dendritic cells (DCs) and drugs transportation into M1-like tumor-associated macrophages (TAMs) and tumor cells via size reduction and increasing positive charge caused by the weakly acidic TME. Such bioactive nanovaccine could remodel the immunosuppressive TME into an effector T cells favorable environment, leading to tumor growth inhibition in prophylactic and therapeutic E.G7-OVA tumor models. Furthermore, combining the bioactive nanovaccine with simultaneous anti-PD-1 antibody treatment leads to a long-term tumor inhibition, based on the optimal timing and sequence of PD-1 blockade against T cell receptor. This research provides a new strategy for the development of efficient cancer immunotherapy.

Background: Anaemia (low haemoglobin [Hb]) is well known to be associated with high mortality and adverse cardiac events following surgical treatment of abdominal aortic aneurysm (AAA). However, little is known about the relationship of AAA volume and Hb level alterations with endovascular repair of AAA. This study aimed to examine the changes in the Hb level and aneurysm volume before and after endovascular aneurysm repair (EVAR) for AAA and determine the relationship between the post-operative Hb level and the volume loss of AAA. Methods: This retrospective study reviewed patients with AAA who underwent EVAR between January 2020 and February 2021 at a tertiary medical centre. The clinical features and medical history of the patients were analysed. Alterations in the Hb level were recorded, and the AAA volume was calculated from computed tomography angiography images before and after EVAR to infer the association between the post-operative Hb level and alterations in AAA volume. Moreover, AAA volume, pre-operative Hb level and medical history were studied to identify the risk factors for anaemia 24 h after EVAR. Results: A total of 74 patients (mean age, 67 ± 7.9 years) were included in this study. The Hb level decreased significantly 24 h after EVAR, and the post-operative Hb level was negatively correlated with AAA volume loss (r = –0.252, p = 0.041). No relationship was observed between AAA volume loss and decrease in the Hb level (r = 0.072, p = 0.571) or between pre-operative AAA volume and decrease in the Hb level (r = 0.072, p = 0.566). Furthermore, 59.5% of the patients (n = 44) developed anaemia 24 h after EVAR. The odds ratio (OR) of anaemia 24 h after EVAR was 5.3 times higher in those with hypertension (OR, 5.304; 95% confidence interval [CI], 1.024–27.424) than in those without the condition. The pre-operative Hb level (or normal Hb level) was a protective factor (OR = 0.909; 95% CI, 0.853–0.969). The area under the receiver operating characteristic curve was 0.840. The post-operative Hb level declined significantly, and AAA volume loss contributed to it. Moreover, hypertension was identified to be a risk factor for anaemia 24 h after EVAR, and pre-operative Hb level was discerned to be a protective factor. Conclusions: The findings suggest that decrease in the Hb level in the early post-EVAR stage warrants the attention of surgeons, especially in patients with a history of hypertension or a low pre-operative Hb level.

Therapeutic approaches of combining conventional photodynamic therapy (PDT) with other adjuvant treatments to sensitize PDT represent an appealing strategy. Herein, a novel synergetic “nanobomb” strategy based on glutathione (GSH)-responsive biodegradation was proposed to effectively destroy tumors expeditiously and accurately. This “nanobomb” was rationally constructed via the simultaneous encapsulation of methylene blue (MB) and l-arginine (L-Arg) into polyethylene glycol (PEG) modified mesoporous organosilicon nanoparticles (MON). The resulting L-Arg/MB@MP initially exhibited prolonged blood circulation, improved bioavailability, and enhanced tumor accumulation in mice after tail vein injection according to the pharmacokinetic investigations, before the nanoparticles were entirely excreted. Under laser irradiation, L-Arg/MB@MP produced remarkable reactive oxygen species (ROS) directly for PDT therapy, while a portion of ROS may oxidize L-Arg to generate nitric oxide (NO) not only for gas therapy (GT) but also serve as a biological messenger to regulate vasodilation to alleviate the tumor hypoxia. Subsequently, the rapidly released NO was further oxidized to reactive nitrogen species, which together with ROS promote immunogenic cell death by inducing G2/M cell-cycle arrest and apoptosis in cancer cells, and eventually resulting in enhanced anti-tumor immune responses. Moreover, the GSH depletion in tumor tissues induced by L-Arg/MB@MP biodegradation can cooperate with GT to amplify the therapeutic effect of PDT. These results demonstrate that this “nanobomb” provides new ideas for clinical translation to treat tumor patients in terms of synergistic PDT-GT nanotherapy in hypoxic-solid tumors.

BackgroundThe effectiveness of psychosocial interventions on quality of life (QOL) among people living with HIV has been validated, including mobile health (mHealth) interventions. However, it is unclear which components of such interventions account for these effects. ObjectiveThis study aims to examine positive coping as a potential mediator of the effects of an mHealth intervention on QOL among people living with HIV. MethodsFor this secondary analysis, we used data from an mHealth-based randomized controlled trial, Run4Love, which was conducted to improve QOL and mental health outcomes of people living with HIV. A total of 300 participants were randomly assigned to the intervention group to receive the adapted cognitive-behavioral stress management courses and regular physical activity promotion or the waitlist control group in a 1:1 ratio. Our analysis focused on positive coping and QOL, which were repeatedly measured at baseline and at 3-, 6-, and 9-month follow-ups. Latent growth curve models were constructed to explore the mediating role of positive coping in the effects of the mHealth intervention on QOL. ResultsPositive coping served as a mediator in the effect of the mHealth intervention on QOL for up to 9 months. The mHealth intervention had a significant and positive indirect effect on the slope of QOL via the slope of positive coping (b=2.592×1.620=4.198, 95% CI 1.189-7.207, P=.006). The direct effect of the intervention was not significant (b=0.552, 95% CI −2.154 to 3.258, P=.69) when controlling for the mediator. ConclusionsThe longitudinal findings suggest that positive coping could be a crucial mediator of the mHealth intervention in enhancing QOL among people living with HIV. These findings underscore the importance of improving positive coping skills in mHealth interventions to improve QOL among people living with HIV.

BackgroundThe dose–response relationship between patient engagement and long-term intervention effects in mobile health (mHealth) interventions are understudied. Studies exploring long-term and potentially changing relationships between patient engagement and health outcomes in mHealth interventions are needed. ObjectiveThis study aims to examine dose–response relationships between patient engagement and 3 psychosocial outcomes in an mHealth intervention, Run4Love, using repeated measurements of outcomes at baseline and 3, 6, and 9 months. MethodsThis study is a secondary analysis using longitudinal data from the Run4Love trial, a randomized controlled trial with 300 people living with HIV and elevated depressive symptoms to examine the effects of a 3-month mHealth intervention on reducing depressive symptoms and improving quality of life (QOL). We examined the relationships between patient engagement and depressive symptoms, QOL, and perceived stress in the intervention group (N=150) using 4–time-point outcome measurements. Patient engagement was assessed using the completion rate of course assignments and frequency of items completed. Cluster analysis was used to categorize patients into high- and low-engagement groups. Generalized linear mixed effects models were conducted to investigate the dose–response relationships between patient engagement and outcomes. ResultsThe cluster analysis identified 2 clusters that were distinctively different from each other. The first cluster comprised 72 participants with good compliance to the intervention, completing an average of 74% (53/72) of intervention items (IQR 0.22). The second cluster comprised 78 participants with low compliance to the intervention, completing an average of 15% (11/72) of intervention items (IQR 0.23). Results of the generalized linear mixed effects models showed that, compared with the low-engagement group, the high-engagement group had a significant reduction in more depressive symptoms (β=−1.93; P=.008) and perceived stress (β=−1.72; P

BackgroundMobile 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. ObjectiveThis 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. MethodsWe 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. ResultsAbout 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. ConclusionsThese 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 RegistrationChinese Clinical Trial Registry ChiCTR-IPR-17012606; https://www.chictr.org.cn/showproj.aspx?proj=21019

Aims. To explore the relationship between gestational diabetes mellitus (GDM) and neonatal cord blood amino acid and carnitine levels after GDM was diagnosed among pregnant women monitoring glycosylated haemoglobin levels of 5.5%-6.4% during mid-late gestation. Methods. In all, 7289 qualified participants were recruited and divided into two groups (GDM and control groups) between 1 July 2015 and 1 July 2020, and all maternal-neonatal data were collected and analyzed at three centers. Results. Interestingly, glycine in cord blood was not only significantly different between groups (15.52 vs. 6.67, P

Abstract Background 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. Methods 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. Discussion 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. Trial registration Chinese Clinical Trial Registry - ChiCTR-IPR-17012606, registered on 07 September 2017.

Abstract Background Previous studies have shown positive association between HIV-related stigma and depression, suicidal ideation, and suicidal attempt among people living with HIV/AIDS (PLWH). But few studies have examined the mechanisms among HIV-related stigma, depression, and suicidal status (suicidal ideation and/or suicidal attempt) in PLWH. The current study examined the relationships among perceived and internalized stigma (PIS), depression, and suicidal status among PLWH in Guangzhou, China using structural equation modeling. Methods Cross-sectional study by convenience sampling was conducted and 411 PLWH were recruited from the Number Eight People’s Hospital from March to June, 2013 in Guangzhou, China. Participants were interviewed on their PIS, depressive symptoms, suicidal status, and socio-demographic characteristics. PLWH who had had suicidal ideation and suicidal attempts since HIV diagnosis were considered to be suicidal. Structural equation model was performed to examine the direct and indirect associations of PIS and suicidal status. Indicators to evaluate goodness of fit of the structural equation model included Chi-square Statistic, Comparative Fit Index (CFI), Root Mean Square Error of Approximation (RMSEA), Standardized Root Mean Square Residual (SRMR), and Weighted Root Mean Square Residual (WRMR). Results More than one-third (38.4%) of the PLWH had depressive symptoms and 32.4% reported suicidal ideation and/or attempt since HIV diagnosis. The global model showed good model fit (Chi-square value = 34.42, CFI = 0.98, RMSEA = 0.03, WRMR = 0.73). Structural equation model revealed that direct pathway of PIS on suicidal status was significant (standardized pathway coefficient = 0.21), and indirect pathway of PIS on suicidal status via depression was also significant (standardized pathway coefficient = 0.24). There was a partial mediating effect of depression in the association between PIS and suicidal status. Conclusions Our findings suggest that PIS is associated with increased depression and the likelihood of suicidal status. Depression is in turn positively associated with suicidal status and plays a mediating role between PIS and suicidal status. Therefore, to reduce suicidal ideation and attempt in PLWH, targeted interventions to reduce PIS and improve mental health status of PLWH are warranted.

Accurate outcome and exposure ascertainment in electronic health record (EHR) data, referred to as EHR phenotyping, relies on the completeness and accuracy of EHR data for each individual. However, some individuals, such as those with a greater comorbidity burden, visit the health care system more frequently and thus have more complete data, compared with others. Ignoring such dependence of exposure and outcome misclassification on visit frequency can bias estimates of associations in EHR analysis. We developed a framework for describing the structure of outcome and exposure misclassification due to informative visit processes in EHR data and assessed the utility of a quantitative bias analysis approach to adjusting for bias induced by informative visit patterns. Using simulations, we found that this method produced unbiased estimates across all informative visit structures, if the phenotype sensitivity and specificity were correctly specified. We applied this method in an example where the association between diabetes and progression-free survival in metastatic breast cancer patients may be subject to informative presence bias. The quantitative bias analysis approach allowed us to evaluate robustness of results to informative presence bias and indicated that findings were unlikely to change across a range of plausible values for phenotype sensitivity and specificity. Researchers using EHR data should carefully consider the informative visit structure reflected in their data and use appropriate approaches such as the quantitative bias analysis approach described here to evaluate robustness of study findings. [ABSTRACT FROM AUTHOR]