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Abstract Parents of children with retinoblastoma, the most common primary ocular malignant tumour in childhood, bear a heavy caregiving burden and are very susceptible to fatigue. However, little is known about their current status of fatigue and factors influencing fatigue; therefore,this study, based on the theory of unpleasant symptoms, and included 317 parents of children with retinoblastoma in China, whose general demographic data were collected, and on whom the fatigue severity scale (FSS), the generalized anxiety disorder (GAD-7) and 2-item patient health questionnaire (PHQ-2) were administered, from 9 March to 1 June 2020. The parents’ FSS score and fatigue incidence were 4.41 ± 1.14 and 67.19%, respectively. The fatigue level was positively correlated with anxiety, depression, education, times of hospitalisations, and treatment types (r = 0.125–0.468, P

BackgroundWhen individuals infected with human immunodeficiency virus (HIV) experience pulmonary infections, they often exhibit severe symptoms and face a grim prognosis. Consequently, early, rapid, and accurate pathogen diagnosis is vital for informing effective treatment strategies. This study aimed to use metagenomic next-generation sequencing (mNGS) and targeted mNGS (tNGS) to elucidate the characteristics of pulmonary infections in HIV and non-HIV individuals.MethodsThis study enrolled 90 patients with pulmonary infection at the Department of Infectious Diseases of The First Hospital of Jilin University from June 2022 to May 2023, and they were divided into HIV (n=46) and non-HIV (n=44) infection groups. Their bronchoalveolar lavage fluid (BALF) was collected for mNGS analysis to evaluate the differences in pulmonary infection pathogens, and tNGS detection was performed on BALF samples from 15 HIV-infected patients.ResultsA total of 37 pathogens were identified in this study, including 21 bacteria, 5 fungi, 5 viruses, 5 mycobacteria, and 1 mycoplasma. The sensitivity of mNGS was 78.9% (71/90), which is significantly higher than that of conventional methods (CTM) (39/90, P=1.5E-8). The combination of mNGS with CTM can greatly enhance the sensitivity of pathogen detection. The prevalence of Pneumocystis jirovecii (82.6% vs. 9.1%), cytomegalovirus (CMV) (58.7% vs. 0%), and Epstein-Barr virus (EBV) (17.4% vs. 2.3%) was significantly higher in the HIV infection group than in the non-HIV infection group (P

Abstract Background In recent years, mobile psychological interventions have proven effective in reducing self-injury and suicide-related behaviors. Therefore, it is essential to continually enhance the user experience and address patients' needs to facilitate the development of mobile mental health interventions. Identifying patients with mobile mental health needs can be challenging for mental health professionals. To address this, we conducted a systematic review of qualitative research to synthesize the needs of patients engaged in self-injury and suicide-related behaviors for mobile and internet-based psychological interventions. Methods This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA) and the Enhancing Transparency in Reporting the Synthesis of Qualitative Research statement (ENTREQ). We explored 11 databases and synthesized the results using thematic analysis. Results Sixteen qualitative and mixed-method studies were included. The study found that the needs of patients with self-injury and suicide-related behaviors for mobile psychological intervention included therapy, technology, culture, privacy, communication, emotional support, personalization, and self-management. Consistent with the Technology Acceptance Model (TAM), the needs of patients with self-injury and suicide-related behaviors are influenced by the perceived ease of use and perceived usefulness of the mobile intervention. However, the findings also highlight the importance and unmet needs of peer support, communication, self-management, and empowerment in using mobile psychological interventions for patients with self-injury and suicide-related behaviors. Conclusions Studies in this area have shown that the needs of patients with self-harm and suicide-related behaviors cover multiple stages, including basic therapeutic and technical needs and advanced emotional needs. This complexity makes it challenging to address the needs of patients engaged in self-injury and suicide-related behaviors through digital interventions. In the future, mental health professionals should be encouraged to participate in multidisciplinary collaborations to expand the use of digital interventions, enhancing remote self-management for patients and providing new strategies for the ongoing care of psychiatric patients. We registered the review protocol on PROSPERO (CRD42022324958).

Lichen sclerosus et atrophicus (LSA) is a chronic inflammatory skin lesion with an undefined cause. It is more commonly found in the genital area, particularly in adolescents, premenopausal women and postmenopausal women. LSA is difficult to treat and often recurs. The primary treatment for LSA involves the administration of potent topical corticosteroids. Dupilumab is increasingly being used for the treatment of itching in non-atopic dermatitis patients but there are few reports on its use for the treatment of LSA. Here, we present a case of LSA in a 61-year-old woman with extensive vulvar itching. Over four months of dupilumab therapy, significant therapeutic effects were observed, including vulvar skin thinning and pruritus relief without adverse reactions.

ObjectivesSeizures are common in children undergoing cardiopulmonary bypass (CPB). Cerebral oxygen saturation (ScO2) by near-infrared spectroscopy is routinely monitored in many centers, but the relations between the levels and changes of ScO2 and brain injuries remain incompletely understood. We aimed to analyze the postoperative profiles of ScO2 and cerebral blood flow velocity in different types of EEG seizures in relation to brain injuries on MRI.MethodsWe monitored continuous EEG and ScO2 in 337 children during the first 48 h after CPB, which were analyzed in 3 h periods. Cerebral blood flow peak systolic velocity (PSV) in the middle cerebral artery was measured daily by transcranial Doppler. Postoperative cerebral MRI was performed before hospital discharge.ResultsBased on the occurrence and spreading types of seizures, patients were divided into three groups as patients without seizures (Group N; n = 309), those with focal seizures (Group F; n = 13), or with secondarily generalized seizures (Group G; n = 15). There were no significant differences in the onset time and duration of seizures and incidence of status epilepticus between the two seizures groups (Ps ≥ 0.27). ScO2 increased significantly faster across Group N, Group G, and Group F during the 48 h (p

Psoriasis and atopic dermatitis (AD) are prevalent inflammatory skin disorders, each stemming from diverse factors, and characterized by recurring episodes. In certain complex cases, the clinical and pathological features exhibit overlapping and atypical characteristics, making accurate clinical diagnosis and targeted treatment a challenge. Psoriasiform dermatitis is the term used to describe such cases. Moreover, when patients have a history of malignancy, the situation becomes even more intricate, resulting in limited treatment options. Biologic therapies have transformed the management of immune-mediated inflammatory diseases, including psoriasis and AD. Meanwhile, the safety of biologics in special populations, especially among patients with a history of malignancy, should be underlined. The selective Janus kinase 1 (JAK1) inhibitor abrocitinib has been approved for the treatment of AD and has showed satisfying efficacy and safety in the treatment of psoriasis in clinical trials. Although unreported, JAK1 inhibitors are thought to have the potential to increase the risk of potential tumors. Apremilast, an oral phosphodiesterase (PDE)-4 inhibitor, is approved for moderate to severe plaque psoriasis. It has been investigated for its efficacy in AD, and is not contraindicated in malignancy. This report presents three cases of psoriasiform dermatitis in patients with a history of malignancy, showcasing significant improvement following treatment with systemic glucocorticoid, abrocitinib, or apremilast.

Abstract Microbial communication can drive coordinated functions through sensing, analyzing and processing signal information, playing critical roles in biomanufacturing and life evolution. However, it is still a great challenge to develop effective methods to construct a microbial communication system with coordinated behaviors. Here, we report an electron transfer triggered redox communication network consisting of three building blocks including signal router, optical verifier and bio-actuator for microbial metabolism regulation and coordination. In the redox communication network, the Fe3+/Fe2+ redox signal can be dynamically and reversibly transduced, channeling electrons directly and specifically into bio-actuator cells through iron oxidation pathway. The redox communication network drives gene expression of electron transfer proteins and simultaneously facilitates the critical reducing power regeneration in the bio-actuator, thus enabling regulation of microbial metabolism. In this way, the redox communication system efficiently promotes the biomanufacturing yield and CO2 fixation rate of bio-actuator. Furthermore, the results demonstrate that this redox communication strategy is applicable both in co-culture and microbial consortia. The proposed electron transfer triggered redox communication strategy in this work could provide an approach for reducing power regeneration and metabolic optimization and could offer insights into improving biomanufacturing efficiency.

Abstract Bacteroides fragilis, one of the potential next-generation probiotics, but its protective mechanism is not yet known. We aimed to characterize the anti-inflammatory effect of B. fragilisATCC25285 and to elucidate its mechanism through in vivo and in vitro experiments. An in vitro model of inflammation by induction of colonic cells with TNF-a, and co-cultured with B. fragilis to detect cell viability, apoptosis and invasive capacity. Furthermore, critical proteins of the TLR/NF-κB pathway and the inflammatory cytokines were measured. For animal trials, C57BL/6 J male mice were orally administered B. fragilis or PBS once daily for 21 days. Colitis was induced by drinking 2.5% DSS from days 0 to 7. The mice were weighed daily and rectal bleeding, stool condition and blood in the stool were recorded. We found that B. fragilis treatment alone was harmless and had no effect on cell viability or apoptosis. While predictably TNF-α decreased cell viability and increased apoptosis, B. fragilis attenuated this deterioration. The NF-κB pathway and inflammatory cytokines IL-6 and IL-1β activated by TNF-α were also blocked by B. fragilis. Notably, the metabolic supernatant of B. fragilis also has an anti-inflammatory effect. Animal studies showed that live B. fragilis rather than dead strain ameliorated DSS-induced colitis, as evidenced by weight loss, shortened colon length and enhanced barrier function. The colonic tissue levels of inflammatory cytokines (TNF-α, IL-1β, IL-6) were decreased and IL-10 was increased as a result of B. fragilis administration. In conclusion, B. fragilis ATCC25285 exhibited anti-inflammatory effects whether in vivo or in vitro, and it may be a potential probiotic agent for improving colitis.

Protocell models play a pivotal role in the exploration of the origin of life. Vesicles are one type of protocell model that have attracted much attention. Simple single-chain amphiphiles (SACs) and organic small molecules (OSMs) possess primitive relevance and were most likely the building blocks of protocells on the early Earth. OSM@SAC vesicles have been considered to be plausible protocell models. Pyrite (FeS2), a mineral with primitive relevance, is ubiquitous in nature and plays a crucial role in the exploration of the origin of life in the mineral–water interface scenario. “How do protocell models based on OSM@SAC vesicles interact with a mineral–water interface scenario that simulates a primitive Earth environment” remains an unresolved question. Hence, we select primitive relevant sodium monododecyl phosphate (SDP), isopentenol (IPN) and pyrite (FeS2) mineral particles to build a protocell model. The model investigates the basic physical and chemical properties of FeS2 particles and reveals the effects of the size, content and duration of interaction of FeS2 particles on IPN@SDP vesicles. This deepens the understanding of protocell growth mechanisms in scenarios of mineral–water interfaces in primitive Earth environments and provides new information for the exploration of the origin of life.

Vessel detection is critical for ensuring maritime transportation and navigational safety, creating a pressing need for detection methodologies that are more efficient, precise, and intelligent in the maritime domain. Nonetheless, accurately detecting vessels across multiple scales remains challenging due to the diversity in vessel types and locations, similarities in ship hull shapes, and disturbances from complex environmental conditions. To address these issues, we introduce an innovative FSN-YOLO framework that utilizes enhanced YOLOv8 with multi-layer attention feature fusion. Specifically, FSN-YOLO employs the backbone structure of FasterNet, enriching feature representations through super-resolution processing with a lightweight Convolutional Neural Network (CNN), thereby achieving a balance between processing speed and model size without compromising accuracy. Furthermore, FSN-YOLO uses the Receptive-Field Attention (RFA) mechanism to adaptively fine-tune the feature responses between channels, significantly boosting the network’s capacity to capture critical information and, in turn, improve the model’s overall performance and enrich the discriminative feature representation of ships. Experimental validation on the Seaship7000 dataset showed that, compared to the baseline YOLOv8l approach, FSN-YOLO considerably increased accuracy, recall rates, and mAP@0.5:0.95 by absolute margins of 0.82%, 1.54%, and 1.56%, respectively, positioning it at the forefront of current state-of-the-art models.

ObjectivesDysnatremia is a common electrolyte disturbance after cardiopulmonary bypass (CPB) surgery for congenital heart disease (CHD) and a known risk factor for adverse neurological events and clinical outcomes. The objective of this study was to evaluate the association of dysnatremia with worse abnormal EEG patterns, brain injuries detected by magnetic resonance imaging (MRI) and early adverse outcomes.MethodsWe monitored continuous EEG in 340 children during the initial 48 h following cardiac surgery. Demographics and clinical characteristics were recorded. Sodium concentrations were measured in the arterial blood gas analysis every 6 h. Hyponatremia and hypernatremia were classified by the average of sodium concentrations over 48 h. Postoperative cerebral MRI was performed before hospital discharge.ResultsIn our patient cohort, dysnatremia was present in 46 (13.5%) patients. Among them, hyponatremia occurred in 21 (6.2%) and hypernatremia in 25 (7.4%). When compared to patients with normonatremia, hyponatremia was not associated with EEG abnormalities and early adverse outcomes (Ps ≥ .14). In hypernatremia group, the CPB time was significantly longer and more frequent use of DHCA (Ps ≤ .049). After adjusting for time, CPB time and the use of DHCA, hypernatremia was significantly associated with worse EEG abnormalities (including background, seizures and pathological delta brushes), more severe brain injuries on MRI (Ps ≤ .04) and trended to be associated with longer postoperative mechanical ventilation time (P = .06).ConclusionHypernatremia and hyponatremia were common in children after cardiac surgery. Hypernatremia, but not hyponatremia, was significantly associated with worse EEG abnormalities and more severe brain injuries on MRI and extended postoperative mechanical ventilation time.

Purpose: To construct a risk assessment model for forecasting the likelihood of myopia in elementary school students. Design: A cross-sectional study. Methods: This study utilized convenient sampling and questionnaire survey to collect data from eligible elementary students and their parents during the coronavirus disease 2019 (COVID-19) pandemic period from March to December 2020. The data were divided into training and testing sets in a 7:3 ratio. Lasso regression was employed to screen variables for inclusion in the model to establish a generalized linear model, with a nomogram model as the final result. Results: The study included 1139 elementary students, comprising 54.5 % male and 45.5 % female participants. A total of 37 variables were obtained, which were analyzed using lasso regression. Cross-validation revealed that the best lambda value was 0.04201788. Five variables affecting myopia were identified: three risk and two protective factors. The three risk factors were student age (OR = 1.32), family location (urban vs. rural, OR = 2.33), and parents' occupation (compared with farmer: worker, OR = 2.03; teacher, OR = 1.62; medical worker, OR = 5.64; self-employed, OR = 1.78; civil servant, OR = 1.65; company employee, OR = 1.45; service industries, OR = 3.38; and others, OR = 3.20). The two protective factors were eye distance score (OR = 0.83) and eye health exercise score (OR = 0.95). The model was verified and showed good accuracy with an AUC of 0.778 and Brier score of 0.122 in addition to satisfactory clinical effects. Conclusions: The model effectively predicted the risk of myopia in elementary school students during the COVID-19 pandemic. Using this model, high-risk groups can be identified to provide a foundation for early intervention and follow-up, thereby reducing the incidence of myopia in this population.

Abstract Background Sturge Weber syndrome (SWS), can cause extensive capillary malformations on the face, head, trunk, and other parts of the body, and the eyes can also suffer optic nerve injury. Secondary glaucoma can cause blindness, which has the characteristics of a relatively hidden onset and unclear pathogenesis. The treatment of SWS secondary glaucoma has always been difficult, and due to the characteristics of the disease, there is uncertainty about the long-term efficacy and safety of various treatment methods for such patients. Methods A total of 105 parents of children with SWS completed a self-designed general information questionnaire, a generalized anxiety questionnaire (GAD-7), a patient health questionnaire (PHQ-2), a stress perception scale (PSS-4), a simple coping scale (SCSQ) and a disease-uncertainty scale (PPUS). Results The total uncertainty score of parents of children with SWS was 79.07 ± 13.24, and the average item score was 2.82 ± 0.47. Multiple linear regression analysis revealed that anxiety and simple coping were the main influencing factors of disease uncertainty among parents of children with SWS (P

IntroductionFamily environment is the primary environment for adolescent growth and development, which is believed to have an important impact on the occurrence of non-suicidal self-injury (NSSI) behavior in adolescents. This study aimed to explore the effects of family environment cognition and cognitive differences perceived by adolescents and their parents on the treatment effects of NSSI in adolescents and to provide more potential perspectives for NSSI treatment.MethodsA one-year prospective longitudinal sub-cohort investigation was carried out among 199 adolescents engaged in NSSI and one of their important guardians from the Longitudinal Psychosomatic Disease Study (LoPDS). The NSSI behaviors of adolescents were evaluated at 3 months, 6 months and 1 year after enrollment. The family environment scale (FES) and NSSI Behavior Questionnaire were used as assessment tools for family environment and adolescents NSSI behaviors. Multiple linear regression was used to investigate the role of family environment perception difference in the treatment effect of adolescent NSSI.ResultsAfter one year of follow-up, the perceived self-injury impulse score in recent 2 weeks, self-injury impulse frequency in recent 2 weeks, total number of self-injury in recent 2 weeks decreased significantly. The higher the adolescent family cohesion (Beta: 1.130, 95% CI: 0.886,1.373; p=0.032), parental family expressiveness (Beta: 0.818, 95% CI: 0.375,1.260; p=0.037) and parental family active-recreational orientation score (Beta: 0.609, 95% CI: 0.236,0.981; p=0.048), the better the treatment effect. However, higher adolescent family conflict (Beta: -0.838, 95% CI: -1.377,-0.298; p=0.024) were associated with lower treatment outcomes. The greater the cognitive difference between parents and adolescents in family cohesion (Beta: -1.307, 95% CI: -2.074,-0.539; p=0.014) and family conflict(Beta: -0.665, 95% CI: -0.919,-0.410; p=0.037), the worse the therapeutic effect of NSSI might be.DiscussionThere were certain differences in the cognition of family relationships between parents and adolescents, and subjective family relationship cognition and cognitive differences had a significant effect on the treatment effect of NSSI in adolescents. Helping them identify the cause of cognitive differences and conducting systematic family therapy from the points of difference may be another perspective to improve the treatment effect of NSSI in adolescents.

IntroductionPlacenta accreta spectrum (PAS) may cause enormous and potentially life-threatening hemorrhage in the intrapartum and postpartum periods in emergency cesarean section. How to reduce the occurrence of emergency cesarean section in patients with severe PAS is the key to reducing the adverse outcomes of them. This study aimed to investigate the impact of emergency cesarean section on the perioperative outcomes of pregnant women with PAS and neonates, and also aimed to explore the risk factors of emergency cesarean section in pregnant women with PAS.Materials and methodsA retrospective investigation was conducted among 163 pregnant women with severe PAS. Of these, 72 were subjected to emergency cesarean sections. Data on the perioperative characteristics of the mothers and neonates were collected. Multivariable linear regression analysis was used to detect associations between maternal and perioperative characteristics and volume of intraoperative bleeding. Binary logical regression was used to analyze the association between maternal preoperative characteristics and emergency cesarean section. Linear regression analysis is used to analyze the relationship between gestational age and emergency cesarean section.ResultsThe risks of emergency cesarean section increase 98, 112, 124, and 62% when the pregnant women with PAS accompanied by GHD, ICP, more prior cesarean deliveries and more severe PAS type, respectively. Noteworthy, the risk of emergency cesarean section decreases 5% when pre-pregnancy BMI increases 1 kg/m2 (OR: 0.95; CI: 0.82, 0.98; p = 0.038). Moreover, there is no significant linear correlation between emergency cesarean section and gestational age.ConclusionGHD, ICP, multiple prior cesarean deliveries and severe PAS type may all increase the risk of emergency cesarean section for pregnant women with PAS, while high pre-pregnancy BMI may be a protective factor due to less activity level. For pregnant women with severe PAS accompanied by these high risk factors, more adequate maternal and fetal monitoring should be carried out in the third trimester to reduce the risk of emergency cesarean section.

Abstract Coronavirus disease 2019 (COVID-19) continues to significantly impact the global population, thus countermeasure platforms that enable rapid development of therapeutics against variants of SARS-CoV-2 are essential. We report use of a phage display human antibody library approach to rapidly identify neutralizing antibodies (nAbs) against SARS-CoV-2. We demonstrate the binding and neutralization capability of two nAbs, STI-2020 and STI-5041, against the SARS-CoV-2 WA-1 strain as well as the Alpha and Beta variants. STI-2020 and STI-5041 were protective when administered intravenously or intranasally in the golden (Syrian) hamster model of COVID-19 challenged with the WA-1 strain or Beta variant. The ability to administer nAbs intravenously and intranasally may have important therapeutic implications and Phase 1 healthy subjects clinical trials are ongoing.

IntroductionCoronavirus disease 2019 has become a major global public health concern in December 2019. However, finding and excluding close contacts of COVID-19 infectors is a critical but difficult issue. This study aimed to introduce a new method of epidemiological investigation named space–time companions, which was adopted in Chengdu, China, in November 2021.MethodsAn observational investigation was conducted during a small outbreak of COVID-19 in Chengdu, China in November 2021. A new method of epidemiological investigation called space–time companion was adopted in this outbreak, which was defined as the one who stayed in the same spatiotemporal grid (range: 800 m * 800 m) with the confirmed COVID-19 infector for more than 10 min in the last 14 days. A flow chart was used to describe the screening process of space–time companions in detail and illustrate the space–time companion epidemic management method.ResultsThe COVID-19 epidemic outbreak in Chengdu was effectively controlled for approximately one incubation period (14 days). After four rounds of space–time companions screening, more than 450,000 space–time companions were screened, including 27 COVID-19 infectors. Moreover, in the subsequent rounds of nucleic acid testing for all people in the city, no infected person were found proving the end of this epidemic outbreak.ConclusionThe space–time companion provides a new idea for screening close contacts of the COVID-19 infector and other similar infectious diseases, which can serve as a supplement to traditional epidemiological history surveys to verify and avoid missing close contacts.

Abstract Background Empagliflozin has been reported to protect endothelial cell function, regardless of diabetes status. However, the role of empagliflozin in microvascular protection during myocardial ischemia reperfusion injury (I/R) has not been fully understood. Methods Electron microscopy, western blots, immunofluorescence, qPCR, mutant plasmid transfection, co-immunoprecipitation were employed to explore whether empagliflozin could alleviate microvascular damage and endothelial injury during cardiac I/R injury. Results In mice, empagliflozin attenuated I/R injury-induced microvascular occlusion and microthrombus formation. In human coronary artery endothelial cells, I/R injury led to adhesive factor upregulation, endothelial nitric oxide synthase inactivation, focal adhesion kinase downregulation, barrier dysfunction, cytoskeletal degradation and cellular apoptosis; however, empagliflozin treatment diminished these effects. Empagliflozin improved mitochondrial oxidative stress, mitochondrial respiration and adenosine triphosphate metabolism in I/R-treated human coronary artery endothelial cells by preventing the phosphorylation of dynamin-related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), thus repressing mitochondrial fission. The protective effects of empagliflozin on mitochondrial homeostasis and endothelial function were abrogated by the re-introduction of phosphorylated Fis1, but not phosphorylated Drp1, suggesting that Fis1 dephosphorylation is the predominant mechanism whereby empagliflozin inhibits mitochondrial fission during I/R injury. Besides, I/R injury induced Fis1 phosphorylation primarily by activating the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) pathway, while empagliflozin inactivated this pathway by exerting anti-oxidative effects. Conclusions These results demonstrated that empagliflozin can protect the microvasculature by inhibiting the DNA-PKcs/Fis1/mitochondrial fission pathway during myocardial I/R injury.

Introduction: Accumulated studies have suggested that hepatitis C virus (HCV) infection is one of the leading causes for hepatocellular carcinoma (HCC). However, the mechanisms underlying the effect of HCV on the occurrence of HCC are still poorly understood. Methods: HCV infection datasets (GSE82177 and GSE17856) and HCC datasets (The Cancer Genome Atlas Liver Hepatocellular Carcinoma and GSE89377) were downloaded from Gene Expression Omnibus or TCGA for analysis. The common differentially expressed genes in the above four datasets were identified by R software. The expression of ubiquitin D (UBD) in HCV-infected HepG2 cells was detected by RT-qPCR and Western blot, respectively. The interaction between NS3 and p53 was detected by co-immunoprecipitation. The influence of UBD on the proliferation and migration ability of HepG2 cells was evaluated by CCK-8 and wound healing assay, respectively. Results: UBD was upregulated in both HCV-infected samples and HCC samples. HCV NS3 interacted with p53 and inhibited its expression. HCV NS3-induced UBD promoted the proliferation and migration of HepG2 cells. Conclusion: Our results suggest that HCV NS3-induced UBD is positively correlated with the development of HCV-related HCC during HCV infection. Targeting UBD could be a potential strategy for preventing and treating HCV-induced HCC.

IntroductionThe COVID-19 pandemic is ongoing, and the world continues to work to defeat it. We designed this study to understand the longitudinal change in the mental health of residents who experienced the initial disease outbreak in China and to explore the long-term influencing factors.MethodsThe Perceived Stress Scale (PSS), Generalized Anxiety Scale (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were administered to the same sample four times: during the initial outbreak (T1), 1 month later (T2), 18 months later (T3), and 26 months later (T4).ResultsA total of 397 participants completed all of the follow ups. The mean PSS scores among the four time points showed significant differences (F = 183.98, P < 0.001), with the highest score at T1 (15.35 ± 7.14), a sharp decline at T2 (11.27 ± 6.27), an obvious rebound at T3 (15.17 ± 7.46), and finally a slight decrease at T4 (14.41 ± 7.99). Among the four mean GAD-7 scores, significant differences were also found (F = 242.0, P < 0.001), with the trend that from T1 (7.42 ± 6.03) to T2 (7.35 ± 5.88), the scores remained steady, while they showed an apparent decline at T3 (5.00 ± 5.30) and no obvious change at T4 (4.91 ± 4.81). There were no significant differences among the mean PHQ-9 scores (F = 1.256, P < 0.284). The long-term influencing factors differed for stress, anxiety and depression, but all three were influenced by a history of psychosis at T4, quarantine status and whether the participants' family members were infected during the initial outbreak.DiscussionThe survey revealed that repeated outbreaks in other areas also had an impact on those who experienced the initial outbreak, with a return of stress, a decline in anxiety, and no change in depression, which provides direction for interventions in the future.

Shisa represents a type of single-transmembrane adaptor protein containing an N-terminal cysteine-rich domain and a proline-rich C-terminal region. Nine shisa subfamily genes have been proposed in most vertebrates; however, some might be species-specific. The number of shisa genes present in zebrafish remains unclear. This study aimed to investigate the evolutionary relationships among shisa family genes in zebrafish (TU strain) using phylogenetic and syntenic analyses. The function of shisa-2 was preliminarily examined via CRISPR/Cas13d-mediated knockdown. Following identification in zebrafish, 10 shisa family genes, namely shisa-1, 2, 3, 4, 5, 6, 7, 8, 9a, and 9b, were classified into three main clades and six subclades. Their encoding proteins contained a cysteine-rich N-terminal domain and a proline-rich C-terminal region containing different motifs. A specific syntenic block containing atp8a2 and shisa-2 was observed to be conserved across all species. Furthermore, all these genes were expressed during embryogenesis. Shisa-2 was expressed in the presomitic mesoderm, somites, and so on. Shisa-2 was identified as a regulator of the expression of the somite formation marker mesp-ab. Overall, our study provides new insights into the evolution of shisa family genes and the control of shisa-2 over the convergent extension cells of somitic precursors in zebrafish.

Abstract Background Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. Half of the patients would slowly progress to end-stage renal disease. However, the potential target for ADPKD treatment is still lacking. Methods Four ADPKD patients and two healthy family members were included in this study. The peripheral blood samples were obtained and tested by the whole exome sequencing (WES). The autosomal mutations in ADPKD patients were retained as candidate sites. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction network (PPI) analyses were performed by clusterProfiler R package. A dataset containing 18 ADPKD patients and three normal samples were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the limma R package. Results A total of six mutant genes were identified based on the dominant genetic pattern and most of them had not been reported to be associated with ADPKD. Furthermore, 19 harmful genes were selected according to the harmfulness of mutation. GO and KEGG enrichment analyses showed that the processes of single-organism cellular process, response to stimulus, plasma membrane, cell periphery, and anion binding as well as cyclic adenosine monophosphate (cAMP) signaling pathway and pathways in cancer were significantly enriched. Through integrating PPI and gene expression analyses, acyl-CoA thioesterase 13 (ACOT13), which has not been reported to be related to ADPKD, and prostaglandin E receptor 2 (PTGER2) were identified as potential genes associated with ADPKD. Conclusions Through combination of WES, gene expression, and PPI network analyses, we identified ACOT13 and PTGER2 as potential ADPKD-related genes.

ObjectivesPatient-initiated hospital violence is a global problem which threatens the safety of health professionals and is indicative of doctor-patient tensions, impeding health system quality and access. The current study aimed to improve the understanding of medical workplace violence (WPV) in China, using authoritative and nationally representative judgment records, and to approach violence prevention strategies.MethodsAll litigation records relating to violence against health professionals between 2013 and 2021 were extracted from the China Judgment Online System. Basic case information, victim characteristics, perpetrator characteristics and the nature of the violence were collated. The relationship between different treatment outcomes and violence was also explored.ResultsNumbers of cases of hospital violence gradually increased from 2013 to a peak in 2016 before gradually decreasing in the following years. The most common perpetrators were patients' relatives (58.2%), followed by patients themselves (38.2%). Only 9 perpetrators had a confirmed history of mental illness and only two were intoxicated with alcohol. More than half of the cases (52.5%) occurred in rural areas and this percentage is even greater for primary health care institutions (71.4%) and secondary hospitals (73.5%). On a departmental level, the highest incidence of medical WPV was found in the emergency (18.9%), pediatrics (13.2%) and obstetrics (11.5%) departments. Violent behaviors, such as stalking, mass occupation of the ward and sharp instrument injury were significantly related to cases not involving patient death (p < 0.05). Disruptive behavior, such as hanging banners, blocking hospital passages, placing flower wreaths and burning paper money were significantly correlated with cases involving patient death (p < 0.01). The interval between a patient's death and the ensuing violence was short, happening on the same day in 54.8% of cases.ConclusionsA comprehensive overview of medical WPV in China is presented and may have utility for the formulation of prevention strategies.

BackgroundViolence against health professionals is a global public health problem. In 2019, a doctor was killed in Civil Aviation General Hospital (CAGH), which triggered national discussion about hospital violence. Sina Weibo, the Chinese version of Twitter, played an important role in this public discussion. The CAGH incident provides us with an opportunity to explore how social media was used in the discussion on violence against doctors.MethodsUsing the built-in search engine of Sina Weibo, a data set containing 542 Chinese micro-blogs was established. Three keywords: Civil Aviation General Hospital, doctor, and knife were used to search for related posts between December 24th, 2019 and January 19th, 2020. We made a content analysis of the posts to investigate: Weibo users' demographics, views about the incident of CAGH, and measures to prevent hospital violence.ResultsOverall, 89.3% of the posts were sent by individual Weibo users, and 10.7% by organizations. Among the individual users, doctors accounted for 27.4%, but only 1.0% came from the legal profession. In addition, 86.7% of the micro-blogs expressed sympathy for the attacked doctor, and 23.1% of the micro-blogs thought that the imperfect medical system was the main cause of the accident. Nearly half of the posts described their disappointment with the government and the society, and 58.6% of medical staff users expressed regret for engaging in medical work. Only 14.2% of micro-blogs put forward some constructive strategies to prevent hospital violence.ConclusionWeibo users played an important role in spreading and discussing the CAGH incident. However, constructive measures to protect doctors were rarely mentioned, and legal opinions were not reflected in time. Hospital violence has caused public dissatisfaction with the government and weakened the professional confidence of medical staff. Occupational health and public health stakeholders must take effective measures to solve workplace violence against doctors.

Objectives The COVID-19 outbreak beginning in late 2019 has resulted in negative emotions among the public. However, many healthcare workers risked their lives by voluntarily travelling to the worst-hit area, Hubei Province, to support antipandemic work. This study explored the mental health changes in these healthcare workers and tried to discover the influencing factors.Design A longitudinal online survey was begun on 8 February 2020, using the snowball sampling method, and this first phase ended on 22 February 2020 (T1). The follow-up survey was conducted from 8 February to 22 February 2021 (T2).Setting Healthcare workers from outside of the Hubei area who went to the province to provide medical assistance.Participants 963 healthcare workers who completed both surveys.Measures Self-Rating Scale of Sleep (SRSS), Generalised Anxiety Scale (GAD-7) and 9-item Patient Health Questionnaire (PHQ-9).Results There were no significant differences in the SRSS scores or in the GAD-7 scores between T1 and T2 (t=0.994, 0.288; p>0.05). However, the PHQ-9 score at T2 was significantly higher than the score at T1 (t=−10.812, p

The burgeoning need to study the applications of nanoparticles (NPs) in biomedical and pharmaceutical fields requires an understanding of their interactions with lipid membranes for further in vivo studies. In this paper, negatively charged egg yolk lecithin liposome (EYL) has been prepared and used as model lipid membranes. Positively charged Mg3Al-layered double hydroxides (LDHs) are viewed as models of clay particles. The ability of the LDH NPs, a two-dimensional nanostructure with an average diameter of 100 nm (LDHs-100) or 500 nm (LDHs-500) to cross the membranes, has been thoroughly investigated via (high-resolution) transmission electron microscopy (TEM), optical microscopy (OM), scanning electron microscopy (SEM), confocal fluorescence microscopy (CLSM), and dynamic light scattering (DLS). The liposomes with an average diameter of 1.5 μm were prepared by the thin-film rehydration method followed by an extrusion technique. A calcein leakage assay and steady-state fluorescence measurement displayed the variation of membrane integrity and polarity of the pyrene-located microenvironment during the interaction between EYL and calcein-interacted LDH NPs (CE-LDHs) or LDH NPs, respectively. These results imply that not only spherical particles but also even more sophisticated nanostructured materials are able to effectively cross the lipid bilayers, thereby engineering new compounds that may be encapsulated for safe and potential use in biomedical applications.

Abstract Background As the outbreak of COVID-19, traditional face-to-face psychological intervention are difficult to achieve, so hotline becomes available and recommended strategies. The callers’ characteristic could help us to study their experiences of emotional distress, as well as the reasons for calling during the pandemic, which can be used to inform future service design and delivery. Methods The information of 1558 callers called our hospital’ s hotline for help from February 3, 2020, to March 16, 2020 were collected in the form of Tick-box and Free text, and the inductive content analysis was undertaken focusing on the reasons for caller engagement. Results It was indicated that more than half of the callers are female (59.7%), mostly between the age of 18–59 (76.5%). The average age was 37.13 ± 13.76 years old. The average duration of a call to the hotline was 10.03 ± 9.84 min. The most frequent description emotional state were anxious (45.1%) and calm (30.3%), with the sub-sequence of scared (18.2%), sad (11.9%), and angry (6.9%). All callers displayed a wide range of reasons for calling, with needing support around their emotion (64.6%), seeking practical help (44.0%), and sleep problems (20.3%) constituting the majority of calls. Among the subthemes, 314 callers thought the epidemic has made them upset, 198 asked questions about the epidemic, and 119 reported their life routines were disrupted. The prevalence of key reasons does not appear to differ over time. Through their feedback, 79.1% agreed that they felt emotionally better after calling, and 95.0% agreed that hotline had helped them. Conclusions During the epidemic, the most concern of the public is still related to epidemics and its adverse effects. Fortunately, the hotline can be an active and effective rescue measure after an emergency happened.

This study aimed to analyze the clinical significance of serum ferritin, procalcitonin (PCT), and C-reactive protein (CRP) in patients with hemorrhagic fever with renal syndrome (HFRS). The demographical, clinical, and laboratory data of 373 patients with HFRS in northeastern China were retrospectively analyzed. The levels of serum ferritin and PCT in severe patients (n = 108) were significantly higher than those in mild patients (n = 265, p < 0.001) and associated with HFRS severity. The area under the receiver operating characteristic curve (AUC) values of serum ferritin and PCT for predicting the severity of HFRS were 0.732 (95% CI 0.678–0.786, p < 0.001) and 0.824 (95% CI 0.773–0.875, p < 0.001), respectively, showing sensitivity and specificity of 0.75 and 0.88 for serum ferritin, and 0.76 and 0.60 for PCT. The CRP level in HFRS with bacterial co-infection (n = 115) was higher than that without bacterial co-infection (n = 258, p < 0.001). The AUC value of CRP for predicting bacterial co-infection was 0.588 (95% CI 0.525–0.652, p < 0.001), showing sensitivity and specificity of 0.43 and 0.76, respectively. The serum ferritin level in non-survivors (n = 14) was significantly higher than in survivors (n = 359, p < 0.001). The AUC value of serum ferritin for predicting mortality was 0.853 (95% CI 0.774–0.933, p < 0.001), showing sensitivity and specificity of 0.933 and 0.739. Serum ferritin and PCT have a robust association with HFRS severity and mortality, which may be promising predictors, and CRP is an effective biomarker to assess bacterial co-infection in HFRS.

Abstract The expansion of the electric power communication network year by year has enabled a large number of intelligent terminals to be accessed exponentially. Massive intelligent terminals connected to the power communication network have a huge processing demand, which causes a heavy maintenance burden on the equipment of communication networks. In order to solve this problem, this study proposes a flexible communication mechanism based on the device‐to‐device (D2D) technique for the intelligent terminals to deal with the processing pressure of massive information in the network. This proposed mechanism introduces where and how to use the D2D technique. In this study, this communication mechanism makes terminals give a high priority to transferring the information of important services. The D2D communication model is formulated for this communication mechanism, and the influence of different conditions on the D2D communication is analysed. The D2D communication mechanism is simulated to optimise the existing network indexes, such as traffic and sum of service level.

Abstract Background Colorectal adenomatous polyps (CAPs) are considered precancerous lesions of colorectal cancer (CRC). The gut microbiota participates in the process of digestion and, in the process, produces metabolites, mainly short-chain fatty acids (SCFAs), secondary bile acids and conjugated linoleic acid (CLA). This study aimed to investigate the gut microbiota constituents and metabolites in the faeces of CAP patients to identify microbiota or metabolites that can be used as sensitive biological predictors and to provide a theoretical basis for the clinical treatment of CAPs. Methods 16S rRNA sequence analysis was used to detect microbial changes in the faeces of CAP patients. qPCR analysis was used to evaluate the ability of the microbiota to produce metabolites, and the contents of metabolites in faeces were detected by ion chromatography and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Results Based on the detection of the gut microbiota, patients with CAPs had increased abundances of Bacteroides and Citrobacter, and the abundances of Weissella and Lactobacillus were decreased. We also explored gene expression, and the abundance of butyrate-producing bacterial genes was significantly increased in the faeces of CAP patients, but those of secondary bile acid-producing and CLA-producing bacterial genes showed no differences in faecal samples. The acetic acid and butyric acid contents were increased in the faeces of the CAP group, and the healthy control group had higher t10,c12-CLA contents. Conclusion The gut microbiota analysis results, assessed in faeces, showed that Bacteroides and Citrobacter were positively correlated with CAPs, which indicated that changes in specific genera might be detrimental to intestinal health. In addition, t10,c12-CLA played an important role in protecting the intestine.

Abstract Background The clinical characteristics of patients with confirmed 2019 novel coronavirus disease (COVID-19) in Jilin Province, China were investigated. Methods Clinical, laboratory, radiology, and treatment data of 41 hospitalized patients with confirmed COVID-19 were retrospectively collected. The population was stratified by disease severity as mild, moderate, or severe, based on guidelines of the National Health and Medical Commission of China. Results The 41 hospitalized patients with COVID-19 were studied, and the median age was 45 years (interquartile range [IQR], 31–53; range, 10–87 years) and 18 patients (43.9%) were female. All of the patients had recently visited Wuhan or other places (ie, Beijing, Thailand) or had Wuhan-related exposure. Common symptoms included fever (32[78%]) and cough (29[70.7%]). All patients were without hepatitis B/C virus hepatitis. CRP (C-reactive protein, 11.3 mg/L [interquartile range {IQR}, 2.45–35.2]) was elevated in 22 patients (53.7%), and cardiac troponin I (1.5 ng/mL [IQR, 0.8–5.0]) was elevated in 41 patients (100%). Chest computed tomographic scans showed bilateral ground glass opacity (GGO) or GGO with consolidation in the lungs of 27(65.9%) patients. 31(75.6%) patients had an abnormal electrocardiograph (ECG). Comparing the three groups, the levels of CRP and cardiac troponin I, GGO distribution in bilateral lungs, and electrocardiogram changes were statistically significant (p

Since its outbreak in Wuhan, Hubei Province China, 2019-coronavirus infected disease (COVID-19) had been widely spread all over the world, the control of which calls for a better understanding of its epidemiology and clinical characteristics. We included 12 confirmed cases of COVID-19 in First Affiliated Hospital of Jilin University from 23 January 2020 to 11 February 2020, which were retrospectively analyzed for epidemiological, demographic, clinical, laboratory, and radiological features. All the patients were confirmed by nucleic acid detection, the average age of whom was 45.25 years (range, 23–79 years). Most patients had a history of Wuhan traveling or had contact with Wuhan travelers or infected cases. Obvious family cluster was observed. Clinical manifestations included fever (12/12), fatigue (10/12), cough (6/12), sore throat (4/12), headache (3/12), and diarrhea (2/12). Only three out of eight patients had pneumonia manifestation on radiography. Most patients had a normal white blood cell (WBC) count and normal or reduced lymphocyte (LY) count. Pneumonia changes were observed in all the four patients who underwent a chest CT scan. Only one elderly patient developed severe pneumonia, while all the rest were mild disease and had a self-limiting course.

Eight members of a big family with laboratory-confirmed COVID-19 pneumonia were admitted to First Hospital of Jilin University, Changchun, China, from 28 January to 5 February 2020. The clinical records, laboratory results, and chest computed tomography (CT) scans were retrospectively reviewed. Throat swab samples were positive for severe acute respiratory syndrome coronavirus 2, confirmed by the Center for Disease Control and Prevention of Changchun. All eight patients had fever of different degrees; and 6, 3, and 2 had cough; diarrhea; and sore throat. With disease progression, the percentage of lymphocytes in older patients increased, CT images worsened, and the ratio of lymphocytes increased when images revealed inflammation absorption. Although the CT images showed ground-glass opacities in the youngest patient, his lymphocyte count did not decrease with mild clinical symptoms, and the images showed that inflammation was quickly absorbed. Only the oldest patient developed critical illness. The C reaction protein (CRP) levels of Patient 5 increased significantly, and the rate of decline was the slowest, while his condition was the most severe. The clinical manifestations of COVID-19 in this family cluster varied with contact, age, and underlying disease. Lymphocyte count and quality of chest CT images appeared inversely associated with disease severity. CRP changes may be an indicator of disease severity and prognosis.

Objectives: To determine blood Brucella DNA loads between brucellosis patients and those without brucellosis. Methods: The patient group included 350 brucellosis patients. The control was composed of 200 subjects without brucellosis. The extracted DNA from blood was tested by quantitative polymerase chain reaction (qPCR). The cutoff value was determined by receiver operating characteristic curve analysis. A portion of the brucellosis patients were monitored by qPCR during therapy. Results: The detection limit of qPCR was between 1E + 01 cfu/μL and 1E + 08 cfu/μL. The standard curve R2 reached 0.998. The cutoff value was 4E + 01 cfu/μL, which was determined by comparison of the patient group and the control. The qPCR assay had a specificity of 100% and a sensitivity of 93.14%. The monitoring results showed that the Brucella DNA load decreased in most patients during the first 4 weeks of treatment. One patient with bad treatment compliance showed a rebound. Conclusions: The qPCR results were in accordance with the course of brucellosis in the clinic. The DNA load often reflects the situation of the Brucella-infected patient. The cutoff value provides an important reference of infection. This qPCR-based method can be used to assist in the diagnosis of brucellosis and to adjust the therapy. Keywords: Brucella, Infection, Course, qPCR, Blood, DNA load

Non-suicidal self-injury (NSSI) in adolescents hospitalized with psychiatric disorders continues to increase after the outbreak of COVID-19. This study aimed to explore the relationship between the pandemic and NSSI among adolescents and whether the composition of psychosocial factors related to NSSI has changed during the pandemic. Through the retrospective analysis of medical records retrieved from the electronic system of the psychiatric hospital located in Chengdu from January 2016 to March 2021, 609 medical records of adolescents were obtained. The main potential psychosocial factors were determined by deductive content analysis. Among the 609 adolescents, 420 subjects had engaged in NSSI, while 189 did not. We found that the percentage of adolescents who had engaged in NSSI in 2016 was only 29.2%, reaching 34.5% in 2017, 45.7% in 2018, 61.3% in 2019, 92.5% in 2020, and 95.9% in 2021. In the binary logistic regression model, female sex (OR = 0.073, 95% CI: 0.028–0.186), older age (OR = 1.234, 95% CI: 1.030–1.478), having a single parent (OR = 7.865, 95% CI: 3.997–15.476), having experienced trauma (OR = 2.192, 95% CI: 1.032–4.654), having experienced social isolation from peers (OR = 8.139, 95% CI: 4.037–16.408), having experienced body-focused bullying (OR = 3.078, 95% CI: 1.295–7.318), overuse of a mobile phone in the parents' opinions (OR = 4.354, 95% CI: 1.380–13.738), having attempted suicide (OR = 9.120, 95% CI: 4.492–18.512), and during the pandemic (time point is January 30, 2020) (OR = 5.399, 95% CI: 1.679–17.357) were the factors that were significantly associated with NSSI. When comparing the differences in psychosocial factors between the pre-pandemic and the during-pandemic groups, the results showed that the family constitution, parent–child relationships, mobile phone overuse, and stressful learning were important factors. Tailored interventions geared towards changed psychosocial factors should be formulated.

Abstract Background The SK-PN-DW cell line was established in 1979 and is commercially available. Despite the use of this cell line as an in vitro model for functional and therapeutic studies of malignant primitive neuroectodermal tumor (PNET), there is a lack of complete information about the genetic alterations that are present at the cytogenetic level. Thus, the current study aimed to characterize the cytogenetic profile of this cell line. Methods Routine G-banded chromosome analysis, fluorescence in situ hybridization, and oligonucleotide array comparative genomic hybridization assays were performed to characterize the chromosomal changes in this cell line. Results The G-banded karyotype analysis showed that the number of chromosomes in this cell line ranged between 36 and 41. Importantly, all cells displayed a loss of chromosomes Y, 11, 13, and 18. However, some cells showed an additional loss of chromosome 10. Additionally, the observed structural changes indicated: a) unbalanced translocation between chromosomes 1 and 7; b) translocation between chromosomes 11 and 22 at breakpoints 11q24 and 22q12, which is a classical translocation that is associated with Ewing sarcoma; c) a derivative chromosome due to a whole arm translocation between chromosomes 16 and 17 at likely breakpoints 16p10 and 17q10; and d) possible rearrangement in the short arm of chromosome 18. Moreover, a variable number of double minutes were also observed in each metaphase cell. Furthermore, the microarray assay results not only demonstrated genomic-wide chromosomal imbalance in this cell line and precisely placed chromosomal breakpoints on unbalanced, rearranged chromosomes, but also revealed information about subtle chromosomal changes and the chromosomal origin of double minutes. Finally, the fluorescence in situ hybridization assay confirmed the findings of the routine cytogenetic analysis and microarrays. Conclusion The accurate determination of the cytogenetic profile of the SK-PN-DW cell line is helpful in enabling the research community to utilize this cell line for future identity and comparability studies, in addition to demonstrating the utility of the complete cytogenetic profile, as a public resource.

Background: Thoracic pain is one of the most frequent chief complaints at emergency departments (EDs). However, a respective workup in cases without clear electrocardiographic signs is complex. In addition, after having ruled out acute coronary syndrome (ACS), patients are often left with an unclear etiology of their symptoms. Ultra-sensitive phonocardiography is already used to rule out stable coronary artery disease (CAD); however, its feasibility in an ED-setting remains unknown. Methods: We prospectively used ultra-sensitive phonocardiography via the CADScor®System to measure hemodynamically stable patients with the chief complaint of chest pain during routine waiting times at a high-volume tertiary ED. Results: A total of 101 patients (49% male; 94% Caucasian; 61 (51–71) years; BMI 28.3 (24.2–31.6)) were enrolled. Patient workflow was not hindered, and no adverse events were recorded. In 80% of cases, a score was successfully calculated, with 74% at the first, 5% at the second, and 1% at the third attempt. Feasibility was judged as 9.0 (±1.8) by the patients, and 8.9 (±2.6) by the investigators on a 10-point Likert scale. Conclusions: Ultra-sensitive phonocardiography was found to be feasible in acute chest pain patients presenting to a tertiary ED. Thus, the CAD score measured during routine waiting times could potentially serve as an additional tool in a diagnostic pathway for thoracic pain.

ObjectiveTo probe markers and molecular mechanisms of the hypoplastic left heart (HLH) by single-cell RNA sequencing (scRNA-seq) and quantitative proteomics analysis.MethodsFollowing data preprocessing, scRNA-seq data of pluripotent stem cell (iPSC)-derived cardiomyocytes from one HLH patient and one control were analyzed by the Seurat package in R. Cell clusters were characterized, which was followed by a pseudotime analysis. Markers in the pseudotime analysis were utilized for functional enrichment analysis. Quantitative proteomics analysis was based on peripheral blood samples from HLH patients without heart failure (HLH-NHF), HLH patients with heart failure (HLH-HF), and healthy controls. Hub genes were identified by the intersection of pseudotime markers and differentially expressed proteins (DE-proteins), which were validated in the GSE77798 dataset, RT-qPCR, and western blot.ResultsCardiomyocytes derived from iPSCs were clustered into mesenchymal stem cells, myocardium, and fibroblast cells. Pseudotime analysis revealed their differentiation trajectory. Markers in the three pseudotime clusters were significantly associated with distinct biological processes and pathways. Finally, three hub genes (MMP2, B2M, and COL5A1) were identified, which were highly expressed in the left (LV) and right (RV) ventricles of HLH patients compared with controls. Furthermore, higher expression levels were detected in HLH patients with or without HF than in controls.ConclusionOur findings elucidate marker genes and molecular mechanisms of HLH, deepening the understanding of the pathogenesis of HLH.

BackgroundAfter the elimination of leprosy in 1995, there were 10-30 newly detected leprosy cases every year in Zhejiang Province, and the epidemiological characteristics of the newly detected leprosy cases have changed. While most of the newly detected cases came from other provinces in China, not Zhejiang, it brought a new challenge for leprosy prevention and control in post- elimination era in Zhejiang, China. This study was aimed to understand the temporal-spatial distribution characteristics of newly detected leprosy cases, and provide the scientific rationales for the development of leprosy control strategy.MethodsData on the demographic of Zhejiang Province from 2011 to 2019 were obtained from the China Information System for Disease Control and Prevention, and the epidemiological data on leprosy cases newly detected in Zhejiang Province from 2011 to 2019 were obtained from the LEPROSY MANAGEMANT INFORMATION SYSTEM IN CHINA (LEPMIS), and temporal-spatial distributions were described. The geographic information system software-ArcGIS 10.4 was used to draw the statistical maps, and Geoda 1.14.0 was used for local spatial autocorrelation analysis (local Getis coefficient method). Ridley-Jopling classification was used to classify the clinical types into I, TT, BT, BB, BL or LL. Two-group classification system developed by the World Health Organization (WHO) was used and cases were classified into multibacillary (MB) type or paucibacillary (PB) type.ResultsA total of 167 leprosy cases were reported in Zhejiang Province during 2011-2019, including 107 cases in males and 60 in females. The mean age at diagnosis was 37.99±14.81 years, and 94.01% of the cases were detected through the examination at skin-clinics. The number of workers, MB cases, G2D cases were 81 (48.50%), 159 (94.01%), 24 (14.37%) respectively, and the rate of early detection increased from 45.16% in 2011 to 90.91% in 2019. Leprosy cases were reported in all the prefectures of Zhejiang except Zhoushan City. The cases in local population accounted for 23.35% (39 cases), and the cases in floating population (especially coming from high epidemic provinces in China) accounted for 76.65% (128 cases). The annual number of newly detected cases showed a decreasing trend, from 31 cases in 2011 to 11 in 2019. Time of the floating population living in Zhejiang Province ranged from several months to more than 10 years. The annual proportion of new cases with G2D declined from 22.58% in 2011 to 9.09% in 2019. The results of local indicators of autocorrelation (LISA) analysis showed that the high-high areas were mainly concentrated in the middle and northeast of Zhejiang Province, while the low-low areas were in the east and southwest.ConclusionA few scattered cases still can be seen in post-elimination era, and there was a spatial clustering of the newly detected leprosy cases in Zhejiang Province. Most of the cases in Zhejiang Province were from other high epidemic provinces in China, which brought a new challenge for leprosy control and prevention in post- elimination era in Zhejiang, and it is also necessary to strengthen the early detection and standard management of the leprosy cases in floating population in Zhejiang.

A reliable prediction of the surface deformation of slopes is vital to better assess the fatalities and economic losses caused by landslides. Many prediction methods have been proposed to estimate the surface deformation of landslides with nonlinear characteristics. However, these methods have low accuracy and poor applicability. In this paper, a new hybrid method for surface deformation prediction was proposed, which was deduced from the Wavelet Analysis, Genetic Algorithm (GA), and Elman Algorithm. In this method, the slope surface deformation was decomposed into a trend component and a periodic component using the time series model, which were trained and predicted utilizing the GA-Elman model. The predicted slope surface deformation was the combination of the trend component and the periodic component. Then, the predicted results of slope surface deformation through GA-Elman were compared with the predicted results through Support Vector Machines (SVM), Extreme Learning Machine (ELM), Back Propagation (BP), and Genetic Algorithm-Back Propagation (GA-BP) models. The comparison was made with reference to the data retrieved from the on-site slopes and the laboratory tests. The results revealed that the proposed method highlighted reliability and could be used with higher accuracy to forecast the slope surface deformation in the process of landslides.

Abstract In clinical pharmacology, the free drug hypothesis has been widely applied in the interpretation of the relationship between pharmacokinetics and pharmacodynamics (PK/PD). The free drug hypothesis assumes that the unbound drug concentration in blood is the same as that in the site of action at steady state. The objective of this study is to demonstrate whether the free drug hypothesis is universally applicable for all drugs. The unbound concentrations of the 18 compounds in blood and in brain interstitial fluids (ISF) at steady state following constant intravenous infusion were simultaneously monitored up to 6 hours via in vivo microdialysis technique. Based on the permeability and efflux ratio (ER), the test compounds can be divided into two classes. Class I includes the compounds with good membrane permeability that are not substrates of efflux transporters (eg, P‐gp, BCRP, and MRPs), whereas Class II includes the compounds that are substrates of efflux transporters. The steady‐state unbound drug concentrations in blood, brain, and CSF are quantitatively very similar for Class I compounds, whereas the steady‐state unbound concentrations in the brain and CSF are significantly lower than those in blood for Class II compounds. These results strongly suggest that the free drug hypothesis is not universal for all drugs but is only applicable for drugs with good permeability that are not substrates of efflux transporters.

Background. The emergence of the NDM-1-positive Klebsiella pneumoniae (K. pneumoniae) strains has led to limited therapeutic options for clinical treatment. Understanding the clinical characteristics, antimicrobial resistance, biofilm assay, and the virulence genes of these isolated strains is of great significance. Methods. The polymerase chain reaction (PCR) was used to screen isolated NDM-1-positive K. pneumoniae. The clinical information of the patients was collected from medical records. The NDM-1-positive K. pneumoniae isolates were subjected to antimicrobial susceptibility testing and multilocus sequence typing. Sixty strains of NDM-1-negative K. pneumoniae isolated during the same period were collected as the control group for the virulence analysis. The virulence phenotype of the strains was preliminarily evaluated by the string test and crystal violet semiquantitative biofilm formation experiment. PCR combined with gene sequencing was used to detect common high toxicity capsule genes (K1, K2, K5, K20, K54, and K57) and common virulence-related genes (entB, ybtS, ureA, ycf, WabG, FimH, uge, iutA, KfuB, aerobactin, rmpA, magA, Alls, IrnN, and VatD). Results. In the 30 nonduplicated NDM-1-positive K. pneumoniae isolates, 43.33% (13/30) of the patients had a history of a stay in the neonatal intensive care unit (NICU). All of the isolates exhibited multidrug resistance. Nine STs were identified, 77% (10/13) strains from the NICU were ST11. The NDM-1-positive K. pneumoniae string tests were all negative, and 35% (21/60) NDM-1-negative K. pneumoniae were positive. The ratios of NDM-1-positive K. pneumoniae isolates biofilm formation ability according to strong, medium, and weak classification were 67%, 23%, and 10%, respectively. NDM-1-negative K. pneumoniae isolates were 60%, 25%, and 15%, respectively. There was no statistical difference between the two groups (t = 0.61, P=0.2723). The virulence-associated genes with more than 80% of detection rates among the 30 NDM-1-positive K. pneumoniae isolates included entB (100%, 30/30), ybtS (93.33%, 28/30), ureA (90%, 27/30), ycf (83.33%, 25/30), and wabG (90%, 27/30). KfuB and iutA were detected at prevalence of 3.33% and 13.33%. vatD, allS, iroN, aerobactin, and rmpA were not detected. In the NDM-1-negative K. pneumoniae, all other 14 virulence genes except VatD were detected. After statistical analysis, FimH, WabG, ycf, iutA, kfuB, aerobactin, rmpA, and Alls virulence genes, P

Abstract Leucine‐rich repeat‐containing G protein‐coupled receptor 5 (LGR5) plays a vital role in the development of malignant tumors; however, its biological role and underlying mechanism in epithelial ovarian cancer (EOC) remain unclear. In this study, we aimed to investigate the biological function and clinical significance of LGR5 in human EOC. We evaluated LGR5 expression in EOC cell lines and tissues from ovarian cancer patients by qPCR, Western blotting, and immunohistochemical analysis. Cell proliferation, colony formation, transwell invasion assay, and scratch‐wound assays were conducted to evaluate the expansion and invasion abilities of EOC cells. Tumor xenograft experiments were performed in female BALB/c athymic nude mice to test cell proliferation in vivo. Western blot analysis was performed to confirm the expression of epithelial‐to‐mesenchymal transition (EMT) signature proteins and their association with Notch1 signaling. The results demonstrated that LGR5 was overexpressed in EOC tissues and cell lines. Aberrant expression of LGR5 was significantly associated with patient age (P = 0.006), tumor histologic type (P

Background and objective The purpose of this study was to explore the status of prevention and nursing on venous thromboembolism (VTE) among perioperative patients with lung cancer in Chinese hospital. Methods A self-designed questionnaire was used to investigate 108 head nurses from tertiary hospitals during the first West China Forum on Chest Enhanced Recovery After Surgery (ERAS). Results (1) Current status of assessment tools and prevention guidelines: 97.22% of the hospitals have carried out VTE risk assessments for surgical patients with lung cancer, 67.59% of the hospitals have established the nursing prevention specifications of VTE. (2) Current status of screening, precaution and follow-up: 56.48% of the hospitals have taken different approach to screen VTE for lung cancer patients in pre-operative period. 90.74% of the hospitals and 52.78% of the hospitals had VTE prophylaxis for hospitalized and discharged patients, but only 17.59% of hospitals were followed up on the incidence of VTE for discharged patients. (3) There was no statistically significant difference in VTE prevention between different type hospitals (P>0.05). But, all patients in the specialist hospital have been fully implemented on VTE risk assessment and VTE prevention (100.00%). Conclusion The clinical staff have already realized the importance of VTE prevention, and the VTE prevention in perioperative patients with lung cancer has received extensive attention. But there is still lack of effective risk assessment tools and standardized guidelines of VTE prevention.

Abstract Background In clinical practice, some patients diagnosed with anxiety disorder (AD) may develop bipolar disorder (BD) many years later, and some cases of AD may be cured by the use of mood stabilizers. However, the relationship between AD and BD should be explored further. Method To track how many cases of AD turned to BD and to discover the differences between them, we recruited 48 patients diagnosed with BD, who were assigned to the BD group for the retrospective analysis, and we also recruited 186 patients diagnosed with AD at enrolment; this latter group was asked to complete follow-up surveys conducted 3 months, 6 months, 12 months and 18 months after the primary stage of the study. We defined another two groups according to the usage of mood stabilizers, the rates of reduction in scores on the Hamilton Anxiety Scale and Yale-Brown Obsessive Compulsive Scale, and the changes in Clinical Global Impression scores at different follow-up times: the anxiety group and the atypical BD group (who used mood stabilizers to treat AD). All subjects also completed the NEO Five-Factor Inventory and supplied blood samples to be tested for several endocrine indices (TSH, T3, FT3, T4, FT4, ACTH,PTC) and inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α, CRP) at enrolment. Results In total, 14 subjects developed BD by the end of the study. One hundred eleven subjects were included in the anxiety group. Sixty-three subjects were assigned to the atypical BD group, and they had similar features to the 48 subjects in the BD group in terms of personality traits, abnormality rates of endocrine indices and levels of inflammatory cytokines. From the anxiety group to the atypical BD group and then the BD group, the age of first onset gradually decreased, while the frequency of onset and the score of suicidal ideation gradually increased. Furthermore, the atypical BD group showed markedly higher levels of TSH, IL-6, TNF-α and CRP than the other two groups. Conclusions Some ADs with unique features might belong to the prodromal stage or the atypical presentation of BD, and recognizing these ADs early will economize many medical resources.

Background and Aim: Increasing evidence shows that the calpain regulatory subunit Capn4 can modulate the proliferation and metastasis of cancer cells, and plays an important role in the development of malignant tumors. However, there is no information on the clinical significance of Capn4 in epithelial ovarian carcinoma (EOC) or the molecular mechanisms by which Capn4 promotes the growth and metastasis of EOC. Therefore, the aim of this study was to clarify the role of Capn4 in EOC. Methods: We evaluated Capn4 and osteopontin (OPN) expression in EOC cell lines and tissues from patients with ovarian cancer by western blotting and immunohistochemical analysis. We then created cell lines with downregulated and upregulated Capn4 expression, using Capn4-targeting small interfering RNA and a pcDNA3.1-Capn4 overexpression vector, respectively, to investigate its function in EOC in vitro. In addition, we investigated the potential mechanism underlying the function of Capn4 by examining the effect of modifying Capn4 expression on Wnt/β-catenin signaling pathway-related genes by western blotting. Results: Capn4 was overexpressed in clinical EOC tissues compared with that in normal ovarian epithelial tissue, and was associated with poor clinical outcomes. Upon silencing or overexpressing Capn4 in EOC cells, we concluded that Capn4 promotes cell proliferation and migration in vitro. Furthermore, Capn4 promoted EOC metastasis by interacting with the Wnt/β-catenin signaling pathway to upregulate OPN expression. Conclusion: Our study indicates that Capn4 plays a critical role in the progression and metastasis of EOC, and could be a potential therapeutic target for EOC management.

Summary: Phospholamban (PLN) is a key regulator of sarcolemma calcium uptake in cardiomyocyte; its inhibitory activity to sarcolemma-endoplasmic reticulum calcium ATPase is regulated by phosphorylation. PLN hypophosphorylation is a common molecular feature in the failing heart. The current study provided evidence at the molecular, cellular, and whole-heart levels to implicate a sarcolemma membrane-targeted protein phosphatase, PP2Ce, as a specific and potent PLN phosphatase. PP2Ce expression was elevated in failing human heart and induced acutely at protein level by β-adrenergic stimulation or oxidative stress in cardiomyocytes. PP2Ce expression in mouse heart blunted β-adrenergic response and exacerbated ischemia/reperfusion injury. Therefore, PP2Ce is a new regulator for cardiac function and pathogenesis. Key Words: heart, phosphatase, phospholamban

Background and objective Though the concept of enhanced recovery after surgery (ERAS) has been progressively known by the surgeons and applied clinically, the current status of its cognition among thoracic surgeons and application in thoracic surgery is still unknown. Based on the analysis of a survey of thoracic surgeons and nurses on chest ERAS during a national conference, we aimed to analyze the status and difficulties of the application of ERAS in thoracic surgery. Methods A total of 773 questionnaires were collected during the first West China chest ERAS Forum and analyzed. The content of the questionnaire can be divided into two parts, including the respondents’ institute and personal information, 10 questions on ERAS. Results (1) Current status of clinical application of ERAS is the concept rather than the practice: 69.6% of the surgeons and 58.7% of the nurses agreed with this view; in addition, 88.5% of the doctors and 85.7% of the nurses believed that the concept of ERAS may be applicable to every branches of surgery; (2) 55.6% of the doctors and 69.1% of the nurses believed that the reason of poor clinical application of ERAS included no mature procedure, lack of consensus and specifications; (3) The best team for the clinical practice of ERAS should be based on surgeon-centered multidisciplinary cooperation and integration of medical care: 62.1% of the surgeons and 70.7% of nurses agreed with this view; (4) 73.7% of the surgeons and 81.9% of the nurses agreed that mean hospital stay, patients’ experience in hospital and social satisfaction should be the evaluation standard of ERAS practice. Conclusion The application of ERAS in thoracic surgery is still the concept rather than the practice. The reason included the lack of clinical applicable specifications and scheme.

Background and objective It has been proven that medium chain triglyceride (MCT) diet was contribute to fast track recovery after surgery in patients with operation. In this study, the benefit of postoperative short term MCT diet support was investigated for non-small cell lung cancer patients who underwent anatomic resection. Methods A prospective study was planned with the approval of our institutional review board. 117 lung cancer patients who underwent anatomic resection in a single medical group between December 2015 and March 2016 were randomized. 62 patients were applied a MCT diet. and 55 patients in the control group who were fed with only normal diet, and the serum albumin levels, anus exhaust time, chest drainage, chest drainage time, the hospitalization time of post operation, average hospital cost were analysed. Results The mean anus exhaust time in MCT group [(27.87±14.38) h] was significantly shorter than that in RDG group [(45.18±8.62) h] (P