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Abstract Background Chronic insomnia increases the risk of various health problems and mental illness. Existing research suggests promise for both transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) in treating chronic insomnia individually. However, the combined effects of tDCS and rTMS on this condition remain unclear. This study aimed to verify the efficacy and safety of tDCS combined with rTMS for the treatment of adult patients with chronic insomnia. Methods This was a randomised double-blind parallel-group controlled study. Overall, 157 participants with chronic insomnia were randomly assigned to one of three neurotherapy regimens: tDCS + rTMS, sham tDCS + rTMS, or tDCS + sham rTMS. All groups received 20 treatment sessions over 4 consecutive weeks. The primary outcome was the change in patients’ sleep as assessed by the Pittsburgh Sleep Quality Index (PSQI) at 2 weeks, 4 weeks, and 3 months of follow-up. The secondary outcome was the assessment of different dimensions of depression and anxiety in patients through the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA), as well as the occurrence of adverse events. Results Throughout the intervention and after the 3-month follow-up, the tDCS + rTMS group had significantly reduced total PSQI scores compared with the other two groups [tDCS + rTMS, 9.21 vs. sham tDCS + rTMS, 10.03; difference − 1.10; 95% confidence interval (CI), − 1.82 to − 0.38; p = 0.003; tDCS + rTMS, 9.21 vs. tDCS + sham rTMS, 10.76; difference − 2.14; 95% CI, − 2.90 to − 1.38; p

Background While sciatic nerve injury has been described as a complication of acetabular fractures, iatrogenic nerve injury remains sparsely reported. This study aims to assess iatrogenic sciatic nerve injuries occurring during acetabular fracture surgery, tracking their neurological recovery and clinical outcomes, and investigating any correlation between recovery and the severity of neurologic injury to facilitate physicians in providing prediction of prognosis. Case Presentation We present two cases of male patients, aged 56 and 22, who developed sciatic palsy due to iatrogenic nerve injury during acetabular fracture surgery. Iatrogenic sciatic nerve injury resulted from operatively treated acetabular fractures. Surgical exploration, involving internal fixation removal and nerve decompression, successfully alleviated symptoms in both cases postoperatively. At the latest follow‐up, one patient achieved full recovery with excellent function, while the other exhibited residual deficits at the L5/S1 root level along with minimal pain. Conclusion Sciatic nerve injury likely stemmed from reduction techniques and internal fixation procedures for the posterior column, particularly when performed with the hip flexed, thereby placing tension on the sciatic nerve. Our case reports underscore the significance of liberal utilization of electrophysiologic examinations and intraoperative monitoring for the prediction of prognosis. Surgical exploration, encompassing internal fixation removal and nerve decompression, represents an effective intervention for resolving sciatic palsy, encompassing both sensory neuropathy and motor symptoms.

Abstract Background Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. Methods In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients’ cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients’ depressive symptoms at baseline and week 2. Results After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p

Background During the COVID-19 pandemic, the global incidence of non-suicidal self-injury (NSSI) has been increasing year by year, especially among adolescents, and it is highly correlated with the level of anxiety among teenagers, particularly within Chinese cultural contexts where parenting styles significantly influence adolescent behavior. Objective This study examines the role of culturally-influenced parenting styles and adolescent coping strategies in relation to anxiety and NSSI behavior, aiming to clarify these multivariate interactions for better understanding and intervention. Methods A cross-sectional survey was conducted with NSSI-diagnosed adolescents from Affiliated Kangning Hospital, Ningbo, China, and healthy adolescents from urban schools. Data on background, parenting styles, coping strategies, and anxiety levels were analyzed using chi-square tests, independent sample t-tests, MANOVA, and regression analysis. Results Adolescents with NSSI reported higher anxiety levels, more punishment and interference, and less emotional warmth from their fathers compared to the non-NSSI group (p

Chlamydia are Gram-negative, obligate intracellular bacterial pathogens that infect eukaryotic cells and reside within a host-derived vacuole known as the inclusion. To facilitate intracellular replication, these bacteria must engage in host-pathogen interactions to obtain nutrients and membranes required for the growth of the inclusion, thereby sustaining prolonged bacterial colonization. Autophagy is a highly conserved process that delivers cytoplasmic substrates to the lysosome for degradation. Pathogens have developed strategies to manipulate and/or exploit autophagy to promote their replication and persistence. This review delineates recent advances in elucidating the interplay between Chlamydia trachomatis infection and autophagy in recent years, emphasizing the intricate strategies employed by both the Chlamydia pathogens and host cells. Gaining a deeper understanding of these interactions could unveil novel strategies for the prevention and treatment of Chlamydia infection.

Abstract With recent advancements in robotic surgery, notable strides have been made in visual question answering (VQA). Existing VQA systems typically generate textual answers to questions but fail to indicate the location of the relevant content within the image. This limitation restricts the interpretative capacity of the VQA models and their ability to explore specific image regions. To address this issue, this study proposes a grounded VQA model for robotic surgery, capable of localizing a specific region during answer prediction. Drawing inspiration from prompt learning in language models, a dual-modality prompt model was developed to enhance precise multimodal information interactions. Specifically, two complementary prompters were introduced to effectively integrate visual and textual prompts into the encoding process of the model. A visual complementary prompter merges visual prompt knowledge with visual information features to guide accurate localization. The textual complementary prompter aligns visual information with textual prompt knowledge and textual information, guiding textual information towards a more accurate inference of the answer. Additionally, a multiple iterative fusion strategy was adopted for comprehensive answer reasoning, to ensure high-quality generation of textual and grounded answers. The experimental results validate the effectiveness of the model, demonstrating its superiority over existing methods on the EndoVis-18 and EndoVis-17 datasets.

Thiamine serves as a cofactor of key enzymes involved in glucose metabolism, and its regulatory role in high-carbohydrate diet has not been reported in crustaceans. In this study, six types of isonitrogen and isolipid diets were formulated at two carbohydrate levels (15 % corn starch for the low-carbohydrate group; 30 % corn starch for the high-carbohydrate group) and three concentrations of thiamine (0, 80 and 160 mg/kg) in Macrobrachium nipponense. The carbohydrate metabolism, antioxidant status, and mRNA expression of genes involved in thiamine transport and autophagy of prawns were investigated. The high-carbohydrate diet supplemented with 160 mg/kg thiamine increased the thiamine transporter 1 (SLC19A2) expression compared to a low-carbohydrate diet or other thiamine concentrations. Supplementation with 160 mg/kg thiamine under a high carbohydrate level significantly increased the pyruvate and lactate content in the hepatopancreas. When supplemented with either 0 or 160 mg/kg thiamine, a high dietary carbohydrate significantly increased glucose transporter 4 (GLUT4) and hexokinase (HK) mRNA expressions compared to a low-carbohydrate diet. Among the high-carbohydrate groups, prawns fed with 160 mg/kg thiamine showed significantly higher mRNA expression of pyruvate dehydrogenase-E1-α (PDH-E1-α) compared to those fed with 0 mg/kg thiamine. The activity of superoxide dismutase (SOD) was found to be highest in prawns fed 160 mg/kg thiamine. Supplementation of the carbohydrate diet with either 80 or 160 mg/kg thiamine led to a significant decrease in malondialdehyde (MDA) content accompanied by a significant decrease in glutathione (GSH) level, regardless of low or high carbohydrate levels. The unc-51 like autophagy activating kinase 1 (ULK1) mRNA expression was markedly influenced by both carbohydrate levels and thiamine concentration. Hence, the administration of 160 mg/kg thiamine can improve the thiamine transport, carbohydrate absorption, glycolysis and the antioxidant properties of M. nipponense when fed a high-carbohydrate diet.

Vancomycin-resistant Enterococcus faecium (E. faecium) infection is associated with higher mortality rates. Previous studies have emphasized the importance of innate immune cells and signalling pathways in clearing E. faecium, but a comprehensive analysis of host-pathogen interactions is lacking. Here, we investigated the interplay of host and E. faecium in a murine model of septic peritonitis. Following injection with a sublethal dose, we observed significantly increased murine sepsis score and histological score, decreased weight and bacterial burden, neutrophils and macrophages infiltration, and comprehensive activation of cytokine-mediated signalling pathway. In mice receiving a lethal dose, hypothermia significantly improved survival, reduced bacterial burden, cytokines, and CD86 expression of MHC-II+ recruited macrophages compared to the normothermia group. A mathematical model constructed by observational data from 80 animals, recapitulated the host-pathogen interplay, and further verified the benefits of hypothermia. These findings indicate that E. faecium triggers a severe activation of cytokine-mediated signalling pathway, and hypothermia can improve outcomes by reducing bacterial burden and inflammation.

ABSTRACTCoxiella burnetii (C. burnetii) is the causative agent of Q fever, a zoonotic disease. Intracellular replication of C. burnetii requires the maturation of a phagolysosome-like compartment known as the replication permissive Coxiella-containing vacuole (CCV). Effector proteins secreted by the Dot/Icm secretion system are indispensable for maturation of a single large CCV by facilitating the fusion of promiscuous vesicles. However, the mechanisms of CCV maintenance and evasion of host cell clearance remain to be defined. Here, we show that C. burnetii secreted Coxiella vacuolar protein E (CvpE) contributes to CCV biogenesis by inducing lysosome-like vacuole (LLV) enlargement. LLV fission by tubulation and autolysosome degradation is impaired in CvpE-expressing cells. Subsequently, we found that CvpE suppresses lysosomal Ca2+ channel transient receptor potential channel mucolipin 1 (TRPML1) activity in an indirect manner, in which CvpE binds phosphatidylinositol 3-phosphate [PI(3)P] and perturbs PIKfyve activity in lysosomes. Finally, the agonist of TRPML1, ML-SA5, inhibits CCV biogenesis and C. burnetii replication. These results provide insight into the mechanisms of CCV maintenance by CvpE and suggest that the agonist of TRPML1 can be a novel potential treatment that does not rely on antibiotics for Q fever by enhancing Coxiella-containing vacuoles (CCVs) fission.

Abstract Mild‐heat photothermal antibacterial therapy avoids heat‐induced damage to normal tissues but causes bacterial tolerance. The use of photothermal therapy in synergy with chemodynamic therapy is expected to address this issue. Herein, two pseudo‐conjugated polymers PM123 with photothermal units and PFc with ferrocene (Fc) units are designed to co‐assemble with DSPE‐mPEG2000 into nanoparticle NPM123/Fc. NPM123/Fc under 1064 nm laser irradiation (NPM123/Fc+NIR‐II) generates mild heat and additionally more toxic ∙OH from endogenous H2O2, displaying a strong synergistic photothermal and chemodynamic effect. NPM123/Fc+NIR‐II gives >90% inhibition rates against MDR ESKAPE pathogens in vitro. Metabolomics analysis unveils that NPM123/Fc+NIR‐II induces bacterial metabolic dysregulation including inhibited nucleic acid synthesis, disordered energy metabolism, enhanced oxidative stress, and elevated DNA damage. Further, NPM123/Fc+NIR‐II possesses >90% bacteriostatic rates at infected wounds in mice, resulting in almost full recovery of infected wounds. Immunodetection and transcriptomics assays disclose that the therapeutic effect is mainly dependent on the inhibition of inflammatory reactions and the promotion of wound healing. What is more, thioketal bonds in NPM123/Fc are susceptible to ROS, making it degradable with highly favorable biosafety in vitro and in vivo. NPM123/Fc+NIR‐II with a unique synergistic antibacterial strategy would be much less prone to select bacterial resistance and represent a promising antibiotics‐alternative anti‐infective measure.

Addressing the complex challenges in dynamic production forecasting for the deep-ultra-deep fractured carbonate reservoirs in the Tarim Basin’s Tahe Oilfield, characterized by numerous influencing factors, strong temporal variations, high non-linearity, and prediction difficulties, We proposes a prediction method based on Gated Recurrent Unit networks (GRU). Initially, the production data and influencing factors are subjected to dimensionality reduction using Pearson correlation coefficient and principal component analysis methods to obtain multi-attribute time series data. Subsequently, deep learning modeling of time series data is conducted using Gated Recurrent Unit networks. The model is then optimized using the Optuna algorithm and applied to the dynamic production forecasting of the deep-ultra-deep fractured carbonate reservoirs in the Tahe Oilfield. The results demonstrate that the Gated Recurrent Unit network model optimized by Optuna excels in the dynamic production forecasting of the Tahe fractured carbonate reservoirs. Compared with the traditional method, the mean absolute error (MAE), the root mean square error (MSE) and the mean absolute percentage error (MAPE) are reduced by 0.04, 0.1 and 1.1, respectively. This method proves to be more adaptable to the production forecasting challenges of deep fractured reservoirs, providing an effective means to enhance model performance. It holds significant practical value and importance in guiding the development of fractured reservoirs.

Background:To explore changes in the first clinic visits in adolescents diagnosed with mood disorders, anxiety disorders, or childhood mood disorders from January 2019 to May 2022 based on outpatient records from a large psychiatric hospital in China.Methods:The medical records of adolescents aged 12–17 years at their first clinic visits from January 2019 to May 2022 were collected at Ningbo Kangning Hospital. Adolescents primarily diagnosed with mood disorders, anxiety disorders, or childhood affective disorders were included in the present study.Results:The results showed that the number of adolescents at their first clinic visits diagnosed with mood disorders, anxiety disorders, and childhood affective disorders according to the International Classification of Diseases-10 (ICD-10) increased each year, with an increase from 2019 to 2020 being greater than that from 2020 to 2021. The mean age at first diagnosis showed a significant trend towards younger age (P < 0.001). The mean age when boys did their first clinic visits in 2021 was significantly younger than that in 2019 (P < 0.05) and the mean age of girls in 2021 was significantly younger than that in 2019 (P < 0.001) and in 2020 (P < 0.001). No difference was found in terms of sex (Chi-square = 7.538, P > 0.05).Conclusion:The number of first clinic visits by adolescent patients with mood, anxiety, or childhood affective disorders increased during the COVID-19 pandemic. The use of universal, selective, and indicated prevention and treatment strategies to buffer children and adolescents from negative mental health outcomes is imperative in the context of the COVID-19 pandemic.

Abstract Background Renal cell carcinoma (RCC) accounts for approximately 2–3% of all adult malignancies. Clear cell renal cell carcinoma (ccRCC), which comprises 70–80% of all RCC cases, is the most common histological subtype. Methods ccRCC transcriptome data and clinical information were downloaded from the TCGA database. We used the TCGA and GEPIA databases to analyze relative expression of BMP1 in various types of human cancer. GEPIA was used to perform survival analysis for BMP1 in various cancer types. Upstream binding miRNAs of BMP1 were obtained through several important target gene prediction tools. StarBase was used to predict candidate miRNAs that may bind to BMP1 and candidate lncRNAs that may bind to hsa-miR-532-3p. We analyzed the association between expression of BMP1 and immune cell infiltration levels in ccRCC using the TIMER website. The relationship between BMP1 expression levels and immune checkpoint expression levels was also investigated. Results BMP1 was upregulated in GBM, HNSC, KIRC, KIRP and STAD and downregulated in KICH and PRAD. Combined with OS and DFS, BMP1 can be used as a biomarker for poor prognosis among patients with KIRC. Through expression analysis, survival analysis and correlation analysis, LINC00685, SLC16A1-AS1, PVT1, VPS9D1-AS1, SNHG15 and the CCDC18-AS1/hsa-miR-532-3p/BMP1 axis were established as the most potential upstream ncRNA-related pathways of BMP1 in ccRCC. Furthermore, we found that BMP1 levels correlated significantly positively with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. Conclusion Our results demonstrate that ncRNA-mediated high expression of BMP1 is associated with poor prognosis and tumor immune infiltration in ccRCC.

The coronavirus disease 2019 (COVID-19) pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a worldwide impact. However, detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse. During the COVID-19 pandemic in Shanghai, China in 2022, samples were collected in a Fangcang shelter hospital, a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center (Shanghai) into a health care facility. Aerosol samples at different sites and intervals around patients and in public areas, surface samples, and pharyngeal swab samples from corresponding patients were included. Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR) assays, followed by sequencing if the cycle threshold (Ct) value was < 30. The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones (37.5%, 104/277), especially around the bed (41.2%, 68/165) and near ventilation inlets (45.2%, 14/31). The prevalence of SARS-CoV-2 around the bed, public areas, and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites. Some surface samples of different personal protective equipment from medical staff had high positivity rates. Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2. There was consistency in virus sequences from the same patient and their environment, and the detected virus sequences matched those of virus strains in circulation during the collection periods, which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital. In summary, the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Abstract Objectives Pseudomonas aeruginosa has intrinsic antibiotic resistance and the strong ability to acquire additional resistance genes. However, a limited number of investigations provide detailed modular structure dissection and evolutionary analysis of accessory genetic elements (AGEs) and associated resistance genes (ARGs) in P. aeruginosa isolates. The objective of this study is to reveal the prevalence and transmission characteristics of ARGs by epidemiological investigation and bioinformatics analysis of AGEs of P. aeruginosa isolates taken from a Chinese hospital. Methods Draft-genome sequencing was conducted for P. aeruginosa clinical isolates (n = 48) collected from a single Chinese hospital between 2019 and 2021. The clones of P. aeruginosa isolates, type 3 secretion system (T3SS)-related virulotypes, and the resistance spectrum were identified using multilocus sequence typing (MLST), polymerase chain reaction (PCR), and antimicrobial susceptibility tests. In addition, 17 of the 48 isolates were fully sequenced. An extensive modular structure dissection and genetic comparison was applied to AGEs of the 17 sequenced P. aeruginosa isolates. Results From the draft-genome sequencing, 13 STs were identified, showing high genetic diversity. BLAST search and PCR detection of T3SS genes (exoT, exoY, exoS, and exoU) revealed that the exoS+/exoU- virulotype dominated. At least 69 kinds of acquired ARGs, involved in resistance to 10 different categories of antimicrobials, were identified in the 48 P. aeruginosa isolates. Detailed genetic dissection and sequence comparisons were applied to 25 AGEs from the 17 isolates, together with five additional prototype AGEs from GenBank. These 30 AGEs were classified into five groups -- integrative and conjugative elements (ICEs), unit transposons, IncpPBL16 plasmids, Incp60512−IMP plasmids, and IncpPA7790 plasmids. Conclusion This study provides a broad-scale and deeper genomics understanding of P. aeruginosa isolates taken from a single Chinese hospital. The isolates collected are characterized by high genetic diversity, high virulence, and multiple drug resistance. The AGEs in P. aeruginosa chromosomes and plasmids, as important genetic platforms for the spread of ARGs, contribute to enhancing the adaptability of P. aeruginosa in hospital settings.

ObjectivesThis study aimed to create and validate a radiomics nomogram for non-invasive preoperative Ki-67 expression level prediction in patients with bladder cancer (BCa) using contrast-enhanced CT radiomics features.MethodsA retrospective analysis of 135 patients was conducted, 79 of whom had high levels of Ki-67 expression and 56 of whom had low levels. For the dimensionality reduction analysis, the best features were chosen using the least absolute shrinkage selection operator and one-way analysis of variance. Then, a radiomics nomogram was created using multiple logistic regression analysis based on radiomics features and clinical independent risk factors. The performance of the model was assessed using the Akaike information criterion (AIC) value, the area under the curve (AUC) value, accuracy, sensitivity, and specificity. The clinical usefulness of the model was assessed using decision curve analysis (DCA).ResultsFinally, to establish a radiomics nomogram, the best 5 features were chosen and integrated with the independent clinical risk factors (T stage) and Rad-score. This radiomics nomogram demonstrated significant correction and discriminating performance in both the training and validation sets, with an AUC of 0.836 and 0.887, respectively. This radiomics nomogram had the lowest AIC value (AIC = 103.16), which was considered to be the best model. When compared to clinical factor model and radiomics signature, DCA demonstrated the more value of the radiomics nomogram.ConclusionEnhanced CT-based radiomics nomogram can better predict Ki-67 expression in BCa patients and can be used for prognosis assessment and clinical decision making.

Choosing a suitable bioaerosol sampler for atmospheric microbial monitoring has been a challenge to researchers interested in environmental microbiology, especially during a pandemic. However, a comprehensive and integrated evaluation method to fully assess bioaerosol sampler performance is still lacking. Herein, we constructed a customized wind tunnel operated at 2–20 km/h wind speed to systematically and efficiently evaluate the performance of six frequently used samplers, where various aerosols, including Arizona test dust, bacterial spores, gram-positive and gram-negative bacteria, phages, and viruses, were generated. After 10 or 60 min of sampling, the physical and biological sampling efficiency and short or long-term sampling capabilities were determined by performing aerodynamic particle size analysis, live microbial culturing, and a qPCR assay. The results showed that AGI-30 and BioSampler impingers have good physical and biological sampling efficiencies for short-term sampling. However, their ability to capture aerosols at low concentrations is restricted. SASS 2300 and BSA-350 wet-wall cyclones had excellent enrichment ratios and high microbial cultivability in both short-term and long-term sampling; however, they were not suitable for quantitative studies of aerosols. Polycarbonate filter samplers showed outstanding performance in physical and long-term sampling but lacked the ability to maintain microbial activity, which can be improved by gelatin filter samplers. However, limitations remain for some fragile microorganisms, such as E. coli phage PhiX174 and coronavirus GX_P2V. In addition, the effects of wind speed and direction should be considered when sampling particles larger than 4 µm. This study provides an improved strategy and guidance for the characterization and selection of a bioaerosol sampler for better measurement and interpretation of collected ambient bioaerosols.

Background Non-invasive brain stimulation has improved cognitive functions in patients with Alzheimer’s disease (AD), and some studies suggest a close relationship between cognition and plasticity. However, the clinical benefits of transcranial direct current stimulation (tDCS) in patients still need to be evaluated.Aims This study examined the role of tDCS in improving cognition and whether the improved cognition is related to altered cortical plasticity.Methods 124 patients with AD were randomly assigned to active tDCS (n=63) or sham tDCS (n=61). The tDCS was applied at the dorsolateral prefrontal cortex for 30 treatment sessions across 6 weeks (5 days per week, 2 days off). The Mini-Mental State Examination and the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) were used for cognition evaluation at baseline, week 2 and week 6. The cortical plasticity was represented by motor-evoked potential (MEP) measured with an electromyogram.Results The results showed that multiple courses of active tDCS can improve the cognitive functions of patients with AD, especially in the memory domain (word recall, recall of test instructions and word recognition). In addition, the damaged MEP level was enhanced following active treatment. In the active tDCS group, the improvements in ADAS-Cog total and subitem (word recall and word recognition) scores were negatively correlated with the enhancement of MEP.Conclusions Our research indicates for the first time that twice-a-day tDCS may improve the cognitive function of patients with AD. This study also suggests that cognitive dysfunction may be related to impaired cortical plasticity, which warrants mechanistic investigations of the relationship between cognition and plasticity in the future.Trial registration number ChiCTR1900021067.

Introduction Adolescent depression has been shown to be associated with many devastating psychosocial outcomes. However, there are many barriers that may prevent depressed individuals from receiving specialised treatment. Virtual reality (VR) technology has shown promise as one avenue for overcoming these challenges. This study first aims to evaluate the effectiveness of VR intervention on adolescent depression symptoms, and second, to determine the intervention’s underlying mechanism of effect using functional near-infrared spectroscopy (fNIRS).Methods and analysis This is a single-centre, prospective, randomised controlled clinical trial. Sixty-six eligible adolescents aged 12–18 years with a diagnosis of depression will be randomised in a 1:1 ratio to either the VR treatment group or the conventional treatment group. All patients for both groups will receive usual treatment during a 4-week intervention period. In addition, patients randomised to VR treatment group (n=33) will complete three 20 min VR sessions including attention, executive function and relaxation training per week. Moreover, 33 healthy adolescents will be recruited as the general population. Primary outcome (ie, depressive symptoms) and secondary outcomes (ie, anxiety symptoms, executive function, treatment emergent symptoms, haemoglobin changes measured by fNIRS) will be collected at preintervention, immediately postintervention and at 4 weeks follow-up. The data assessor and analyst will be blinded to group membership.Ethics and dissemination Ethical approval has been obtained from the Ethics Committee of Lishui Second People’s Hospital. Written informed consent will be obtained for all participants. Results will be disseminated through peer-reviewed journals, national or international conference presentations, media outlets, the internet and various community activities.Trial registration number ChiCTR2300067747.

Providencia as an opportunistic pathogen can cause serious infection, and moreover the emergence of multi-drug-resistant Providencia strains poses a potentially life-threatening risk to public health. However, a comprehensive genomic study to reveal the population structure and dissemination of Providencia is still lacking. In this study, we conducted a genomic epidemiology analysis on the 580 global sequenced Providencia isolates, including 257 ones sequenced in this study (42 ones were fully sequenced). We established a genome sequence-based species classification scheme for Providencia, redefining the conventional 11 Providencia species into seven genocomplexes that were further divided into 18 genospecies, providing an extensively updated reference for Providencia species discrimination based on the largest Providencia genome dataset to date. We then dissected the profile of antimicrobial resistance genes and the prevalence of multi-drug-resistant Providencia strains among these genocomplexes/genospecies, disclosing the presence of diverse and abundant antimicrobial resistance genes and high resistance ratios against multiple classes of drugs in Providencia. We further dissected the genetic basis for the spread of blaNDM-1 in Providencia. blaNDM-1 genes were mainly carried by five incompatible (Inc) groups of plasmids: IncC, IncW, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001, and the last three were newly designated in this study. By tracking the spread of blaNDM-1-carrying plasmids, IncC, IncpPROV114-NR, IncpCHS4.1-3, and IncpPrY2001 plasmids were found to be highly involved in parallel horizontal transfer or vertical clonal expansion of blaNDM-1 among Providencia. Overall, our study provided a comprehensive genomic view of species differentiation, antimicrobial resistance prevalence, and plasmid-mediated blaNDM-1 dissemination in Providencia.

ABSTRACTThe emergence of antibiotic-resistant Aeromonas strains in clinical settings has presented an escalating burden on human and public health. The dissemination of antibiotic resistance in Aeromonas is predominantly facilitated by chromosome-borne accessory genetic elements, although the existing literature on this subject remains limited. Hence, the primary objective of this study is to comprehensively investigate the genomic characteristics of chromosome-borne accessory genetic elements in Aeromonas. Moreover, the study aims to uncover novel genetic environments associated with antibiotic resistance on these elements. Aeromonas were screened from nonduplicated strains collected from two tertiary hospitals in China. Complete sequencing and population genetics analysis were performed. BLAST analysis was employed to identify related elements. All newly identified elements were subjected to detailed sequence annotation, dissection, and comparison. We identified and newly designated 19 chromosomal elements, including 18 integrative and mobilizable elements (IMEs) that could be classified into four categories: Tn6737-related, Tn6836-related, Tn6840-related, and Tn6844a-related IMEs. Each class exhibited a distinct pattern in the types of resistance genes carried by the IMEs. Several novel antibiotic resistance genetic environments were uncovered in these elements. Notably, we report the first identification of the blaOXA-10 gene and blaVEB-1 gene in clinical A. veronii genome, the first presence of a tetA(E)–tetR(E) resistance gene environment within the backbone region in IMEs, and a new mcr-3.15 resistance gene environment. The implications of these findings are substantial, as they provide new insights into the evolution, structure, and dissemination of chromosomal-borne accessory elements.

Antibiotics use in aquaculture cause multiple adverse effects on aquatic animal health. Accordingly, studies on alternative approaches to antibiotics in aquaculture are urgently required. This study investigated the effects of dietary postbiotics as an alternative to florfenicol antibiotic on growth performance, survival rate, antioxidant capacity, non-specific immunity, and gut health of juvenile oriental river prawn (Macrobrachium nipponense). Seven isonitrogenous and isocaloric experimental diets were formulated containing 0% (control), 0.25%, 0.5%, 1%, 2% and 4% postbiotics. These experimental diets were fed to three replicates of 70 juvenile prawns (initial weight 0.110 ± 0.010 g) for eight weeks. In addition, a diet containing 0.2% florfenicol (FFC0.2) was included as the antibiotic treatment, which was fed to the prawns for two weeks. Results showed that feeding the prawns on the postbiotics diets improved weight gain and survival rate. The prawns fed on the antibiotics or postbiotics diets increased antioxidant capacity in the hepatopancreas. Moreover, the prawns fed on the postbiotics diets increased significantly non-specific immunity. The optimum amount of postbiotics required for maximum non-specific immunity was 0.76%, 0.86% and 2.85% based on acid phosphatase, alkaline phosphatase and phenoloxidase activities, respectively. The prawns fed on the postbiotics diets upregulated significantly the mRNA expression of immunity related genes, which were downregulated significantly in the prawns fed on the FFC0.2 diet. Furthemore, the prawns fed on the 1% and 2% postbiotics diets had longer microvilli with closely packed intestinal epithelial cell and basement membrane. In summary, supplementing 0.76 to 2.66% postbiotics in the diets for M. nipponense improves growth performance, survival rate, antioxidant capacity, non-specific immunity and gut health compared with florfenicol antibiotic.

The corona virus disease 2019 (COVID-19) is an epidemic pneumonia caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition to pulmonary symptoms and a variety of physical symptoms, patients also experience symptoms of cognitive impairment. Previous studies have shown that many patients will experience varying degrees of cognitive decline in the subacute and prognostic stages after having COVID-19. Then, what are the factors that lead to cognitive decline? This article reviews and analyzes the inherent factors before the onset of the disease, the factors directly related to the disease, and the factors of hospital admission. In addition, this paper also summarizes the evaluation methods of cognitive decline and the possible mechanisms of the pathogenesis, thus providing corresponding clinical intervention ideas for inhibiting or regulating related factors.

Abstract Background Based on our experiences, we found that a kind of elbow injury is characterized by an olecranon fracture accompanied by elbow joint posterior dislocation with the proximal radioulnar joint intact. The aim of this study was to better define this kind of severe elbow instability, which has not been previously reported. Methods We retrospectively analyzed all patients with olecranon fractures who were treated at our institution from January 2013 to April 2021. Data on these patient demographics, injury characteristics, preoperative and postoperative imaging, surgical management, and outcomes were recorded and analyzed. We also made the inclusion criteria and exclusion criteria. Results A total of 309 patients were diagnosed olecranon fractures in our institution, and ten patients met the inclusion criteria, 9 males and 1 female, with an average age of 40.6 ± 12.7 years (26–68 years). Eight patients (80%) were comminuted, and two were oblique olecranon fracture. Nine patients (90%) suffered coronoid process fractures, eight fractures were type III, and one was type II. Eight patients (80%) suffered radial head fractures, seven fractures were type II, and one was type III. All patients suffered lateral collateral ligament complex injury. All patients underwent surgical management and were followed up on average for 15.8 ± 3.2 months (12–20 months). The motion of the elbow and functional outcome were evaluated with several methods. The mean arc of the elbow movement was 131.6° ± 6.0° (124°–140°), and the mean arc of the forearm rotation was 158.5° ± 17.8° (128°–180°). Nine patients’ functional results according to the Mayo Elbow Performance Score (MEPS) were excellent with a mean score of 96.5 ± 5.3 points (85–100 points), and another was good. The mean score according to the Broberg and Morrey functional rating index was 98.8 ± 2.5 points (92–100 points), nine patients were excellent, and another was good. The mean Disabilities of the Arm, Shoulder, and Hand (DASH) score was 0.75 ± 1.2 points (0–3.3 points). Conclusions Trans-olecranon fracture posterior dislocation is a rare injury and has unique characteristics, and it is a kind of complex elbow instability involving the coronoid process and radial head fractures. After bony structure is restored, the repairment of lateral collateral ligament complex is also important to the stability of the elbow joint. Correct understanding of this kind of injury and reasonable treatment plan can achieve good function.

Improving the activation performance and increasing the hydrogen storage capacity are the main problems faced by TiFe-based alloys. In this paper, alloys with chemical composition Ti1.1-xPrxFe0.8Mn0.2 (x = 0, 0.02, 0.04, 0.06, 0.08) are designed to achieve a reversible hydrogen storage capacity of 1.81 wt% in 15 min, which is close to the theoretical hydrogen storage capacity of TiFe alloy of 1.86 wt%. Alloys with Pr content x ≥ 0.04 can be directly activated without the incubation period. Transmission electron microscopy analysis found that doping Pr introduced TiFe (111) crystal plane with smaller surface energy, makes it easy for hydrogen atoms to diffuse from the surface to interior. Moreover, the addition of Pr significantly refines the grains and introduces a large number of grain boundaries and defects, improving the activation rate and kinetics. The physisorption results show that the specific surface area of the TiFe-based alloy after hydrogen absorption is significantly increased by doping Pr.

Background: Non–small cell lung cancer (NSCLC) with TP53 mutations has a worse prognosis. It was generally more resistant to chemotherapy and radiation. Our aim was to investigate the correlation between the TP53 co-mutated gene and clinical features, and prognostic value in patients with NSCLC. Methods: Seventy-three patients with a diagnosis of NSCLC at our hospital were recruited. They were divided into the TP53 mutation status (minor) ( TP53 MU) and TP53 wild-type (major) ( TP53 WT) groups according to their clinical characteristics after their mutation data and clinical information were collected. Serum markers were compared between groups using Mann-Whitney U test. Other clinical factors were compared between groups using χ2 test and Fisher exact test. The log-rank test was used to compare survival curves. Results: Of the 73 patients with NSCLC, 37 (50.68%) were found to carry TP53 mutation. TP53 MU and TP53 WT groups (n = 36) showed a significant difference in the number of smokers, incidence of squamous cell carcinoma, EGFR mutation, and number of advanced patients (P

Abstract Background Reports on traumatic sciatic nerve injury associated with acetabular fracture are rare. In this study, we investigated the demographics of these injuries, their clinical characteristics, management, and factors potentially influencing neurological recovery. Methods We retrospectively reviewed all patients diagnosed to have acetabular fracture at our trauma center between January 2014 and June 2021. Data on patient demographics, characteristics of sciatic nerve injury, neurological recovery, factors potentially influencing neurological recovery were analyzed. Results Eighteen patients (bilateral in one case) met the diagnostic criteria. All these injuries involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Four of the 19 sides with traumatic sciatic nerve injury involved the common peroneal nerve division and 15 involved both the common peroneal and tibial nerve divisions. Seventeen patients (18 sides) underwent intraoperative nerve exploration, which revealed abnormalities in 7 sides and no obvious abnormality in 11 sides. At the last follow-up, 10 sides (52.6%) had complete recovery and 9 (47.4%) had partial recovery; the difference was statistically significant between those with or without abnormal nerve damage during exploration (P = 0.046). Linear regression analysis showed that a nerve abnormality detected intraoperatively was a predictor of nerve recovery (P = 0.009). The mean recovery time was significantly longer for partial recovery than for complete recovery (13.78 months vs. 6.70 months; P = 0.001). Conclusions All the injuries in this series involved the posterior wall or posterior column, and most patients had posterior dislocation of the hip joint. Damage to the common peroneal nerve division was more severe than that to the tibial nerve division preoperatively. However, the degree of recovery of the common peroneal division was not worse than that of the tibial division. There was a relationship between the degree of neurological recovery and whether there was an abnormality at the time of intraoperative nerve exploration. Patients with partial recovery took longer to recover.

The rapid spread of carbapenemase-producing Klebsiella pneumoniae (cpKP) poses serious threats to public health; however, the underlying genetic basis for its dissemination is still unknown. We conducted a comprehensive genomic epidemiology analysis on 420 cpKP isolates collected from 70 hospitals in 24 provinces/autonomous regions/municipalities of China during 2009–2017 by short-/long-read sequencing. The results showed that most cpKP isolates were categorized into clonal group 258 (CG258), in which ST11 was the dominant clone. Phylogenetic analysis revealed three major clades including the top one of Clade 3 for CG258 cpKP isolates. Additionally, carbapenemase gene analysis indicated that blaKPC was dominant in the cpKP isolates, and most blaKPC genes were located in five major incompatibility (Inc) groups of blaKPC-harboring plasmids. Importantly, three advantageous combinations of host–blaKPC-carrying plasmid (Clade 3.1+3.2–IncFIIpHN7A8, Clade 3.1+3.2–IncFIIpHN7A8:IncR, and Clade 3.3–IncFIIpHN7A8:IncpA1763-KPC) were identified to confer cpKP isolates the advantages in both genotypes (strong correlation/coevolution) and phenotypes (resistance/growth/competition) to facilitate the nationwide spread of ST11/CG258 cpKP. Intriguingly, Bayesian skyline analysis illustrated that the three advantageous combinations might be directly associated with the strong population expansion during 2007–2008 and subsequent maintenance of the population of ST11/CG258 cpKP after 2008. We then examined drug resistance profiles of these cpKP isolates and proposed combination treatment regimens for CG258/non-CG258 cpKP infections. Thus, the findings of our systematical analysis shed light on the molecular epidemiology and genetic basis for the dissemination of ST11/CG258 cpKP in China, and much emphasis should be given to the close monitoring of advantageous cpKP–plasmid combinations.

Abstract Diffuse alveolar damage (DAD) triggers neutrophilic inflammation in damaged tissues of the lung, but little is known about the distinct roles of tissue structural cells in modulating the recruitment of neutrophils to damaged areas. Here, by combining single‐cell and spatial transcriptomics, and using quantitative assays, we systematically analyze inflammatory cell states in a mouse model of DAD‐induced neutrophilic inflammation after aerosolized intratracheal inoculation with ricin toxin. We show that homeostatic resident fibroblasts switch to a hyper‐inflammatory state, and the subsequent occurrence of a CXCL1‐CXCR2 chemokine axis between activated fibroblasts (AFib) as the signal sender and neutrophils as the signal receiver triggers further neutrophil recruitment. We also identify an anatomically localized inflamed niche (characterized by a close‐knit spatial intercellular contact between recruited neutrophils and AFib) in peribronchial regions that facilitate the pulmonary inflammation outbreak. Our findings identify an intricate interplay between hyper‐inflammatory fibroblasts and neutrophils and provide an overarching profile of dynamically changing inflammatory microenvironments during DAD progression.

ABSTRACT Three novel imipenemase (IMP)-type metallo-β-lactamases (MBLs), referred to as IMP-89, IMP-91, and IMP-96, were detected in three clinical isolates from China. Antimicrobial susceptibility tests indicated these novel enzymes were resistant to most β-lactams, and IMP-96 with a Ser262Gly mutation had higher activity against meropenem than its point mutant. We then collected sequence data on all 91 available IMP variants for phylogenetic analysis. To further analyze the genetic environment of blaIMP, an extensive comparison was applied to nine accessory genetic elements (AGEs), including six sequenced blaIMP-carrying AGEs in this study and three others from GenBank. These nine AGEs were divided into three groups: three IncpJBCL41 plasmids, Tn6417 and its two derivatives, and three Tn6879-related integrative and conjugative elements (ICEs). All blaIMP genes in this study were captured by class 1 integrons. In the integrons, blaIMP genes usually coexisted with other resistance genes, which further impeded clinical antibacterial treatment. The emergence of new IMP variants and the diversity and complexity of their genetic environment make the prevention and control of drug-resistant strains critical, requiring serious attention from clinical and public health management departments. IMPORTANCE The spread of IMP-type MBLs has increased dramatically in recent years. We discovered three novel IMP variants from three clinical isolates in China. We summarized the classification and evolutionary relationship of all available IMP variants. Moreover, we detailed the genetic characteristics of blaIMP-carrying accessory genetic elements in five clinical isolates. Given the risk of rapid and extensive spread of blaIMP genes, we suggest that continuous surveillance is crucial to combat the acquisition and transmission of blaIMP genes by bacteria, which can impede clinical therapy effectiveness.

Objective: The combined use of transcranial magnetic stimulation and electroencephalography (TMS-EEG), as a powerful technique that can non-invasively probe the state of the brain, can be used as a method to study neurophysiological markers in the field of psychiatric disorders and discover potential diagnostic predictors. This study used TMS-evoked potentials (TEPs) to study the cortical activity of patients with major depressive disorder depression (MDD) and the correlation with clinical symptoms to provide an electrophysiological basis for the clinical diagnosis.Methods: A total of 41 patients and 42 healthy controls were recruited to study. Using TMS-EEG techniques to measure the left dorsolateral prefrontal cortex (DLPFC) ‘s TEP index and evaluate the clinical symptoms of MDD patients using the Hamilton Depression Scale-24 (HAMD-24).Results: MDD subjects performing TMS-EEG on the DLPFC showed lower cortical excitability P60 index levels than healthy controls. Further analysis revealed that the degree of P60 excitability within the DLPFC of MDD patients was significantly negatively correlated with the severity of depression.Conclusion: The low levels of P60 exhibited in DLPFC reflect low excitability in MDD; the P60 component can be used as a biomarker for MDD in clinical assessment tools.

Flexibly and actively updating expectations based on feedback is crucial for navigating daily life. Previous research has shown that people with schizophrenia (PSZ) have difficulty adjusting their expectations. However, there are studies suggesting otherwise. To explore this further, we used a novel trial-based expectation updating paradigm called attribute amnesia. In the task, the participants needed to report the location of a target stimulus among distractors in pre-surprise trials. In the surprise trial, they were unexpectedly asked to report the identity of the target before reporting its location. Afterward, control trials were conducted whereby the participants were asked the same questions as in the surprise trial. Notably, the surprise trial and control trials were nearly identical, except that the participants expected to be asked about identity information in the control trials but not in the surprise trial. Thus, an improvement in identity reporting accuracy in the control trials in comparison with the surprise trial indicated active updating of expectations. In the current study, a total of 63 PSZ and 60 healthy control subjects (HCS) were enrolled. We found that both the PSZ and the HCS were unable to report information that they had fully attended to (i.e., identity) in the surprise trial. However, both groups showed a significant improvement in reporting identity information even in the first control trial. Critically, there was no significant difference in the magnitude of improvement between the two groups. The current findings indicate that PSZ have the ability to update their expectations as quickly and flexibly as HCS, at least in the context of the current task. The possible factors that might contribute to the discrepancy regarding expectation updating are discussed.

Background Penetrating spinal cord injury (PSCI) with retained foreign bodies (RFB) is rarely observed in clinics and may result in a complete or incomplete neurological deficit. This study was performed to appraise the treatment effect of laminectomy for PSCI with RFB. Case Presentation This study presented three patients referred to a tertiary hospital between August 2011 and October 2018 due to PSCI with RFB and receiving laminectomy. The first patient was a 25‐year‐old female with a butcher's knife piercing the T9 lamina and T10 vertebral body obliquely; the second was a 49‐year‐old male who suffered a perforating wound of the cervical spinal canal and injury of vertebral artery from foreign glass, while the third was a 60‐year‐old male with a wooden stick penetrating stomach and terminating in the L1 lamina. The first and second patients immediately underwent laminectomy for debridement and removal of RFB, while the third received two‐staged operations to remove the retained stick thoroughly. Unfortunately cases 1 and 3 eventually resulted in total paralysis and case 2 revealed no improvement in myodynamia. Then, Medline/PubMed, Embase and the Cochrane Library were systematically searched, and 23 articles involving 25 additional cases with this kind of injury were included for analysis. Conclusions The optimal treatment strategy for penetrating spinal cord injury with retained foreign bodies remains challenging and should be assessed case‐by‐case. If possible, surgical removal of foreign bodies by laminectomy is preferred immediately to prevent delayed presentation and persistent contamination. Meanwhile, a multidisciplinary team is needed to address concomitant injuries.

Objective To present a novel approach for the anatomic reconstruction of the posterior tibialis tendon (PTT) in restoring plantar insertions and evaluate its efficiency in treating flexible adult‐acquired flatfoot deformity (AAFD) caused by PTT dysfunction. Methods For AAFD treatment, a novel PTT reconstruction method was presented. The current study involved 16 patients, including three men, and 13 women, from August 2017 to July 2019. The mean age was 43.2 ± 15.1 years (21–64 years). The innovative PTT repair method was used on all patients. The treatment involved performing a traditional Flexor Digitorum Longus (FDL) transfer in the navicular tuberosity and suturing the plantar insertions to FDL as tension was applied to tighten the plantar structures of the foot. The results were retrospectively analyzed. The clinical outcome was assessed using the pain visual analogue scale (VAS), the satisfaction VAS, and the American Orthopedic Foot and Ankle Society ankle–hindfoot scale (AOFAS‐AH). Isokinetic testing was performed using a dynamometer at 60°/s and 120°/s for inversion/eversion and plantarflexion/dorsiflexion, respectively, to determine the mean peak torque. Radiographic measurements were employed to assess the outcomes. Results Bone surgeries combined with the modified anatomic PTT reconstruction were performed on patients with medializing calcaneal osteotomy in 12 (75%) patients and subtalar joint fusion in four (25%) patients. The branch linking to the plantar insertions was detected in every case, with an average width of 3.5 ± 0.8 mm (3.1–4.3 mm). All patients were followed up for the mean of 16.8 ± 1.8 months (range, 15–20 months). The average postoperative functional scores, including pain VAS, satisfaction VAS, total AOFAS‐AH, and all AOFAS‐AH sub‐scales, steadily improved during the follow‐up. In the last follow‐up, isokinetic testing revealed no loss of plantarflexion strength (p = 0.350 and 0.098) and significant improvement in the inversion strength (p = 0.007 and 0.008) in the operated ankles at 60°/s and 120°/s. Radiographic outcomes, particularly the talar head uncovering, improved significantly after more than a year (p

Abstract In recent years, human motion prediction has become an active research topic in computer vision. However, owing to the complexity and stochastic nature of human motion, it remains a challenging problem. In previous works, human motion prediction has always been treated as a typical inter-sequence problem, and most works have aimed to capture the temporal dependence between successive frames. However, although these approaches focused on the effects of the temporal dimension, they rarely considered the correlation between different joints in space. Thus, the spatio-temporal coupling of human joints is considered, to propose a novel spatio-temporal network based on a transformer and a gragh convolutional network (GCN) (STTG-Net). The temporal transformer is used to capture the global temporal dependencies, and the spatial GCN module is used to establish local spatial correlations between the joints for each frame. To overcome the problems of error accumulation and discontinuity in the motion prediction, a revision method based on fusion strategy is also proposed, in which the current prediction frame is fused with the previous frame. The experimental results show that the proposed prediction method has less prediction error and the prediction motion is smoother than previous prediction methods. The effectiveness of the proposed method is also demonstrated comparing it with the state-of-the-art method on the Human3.6 M dataset.

Abstract Purpose To evaluate the effectiveness of pelvic packing (PP) in pelvic fracture patients with hemodynamic instability. Materials and methods Three databases—PubMed, Embase and the Cochrane Library—were systematically searched to identify studies presenting comparisons between a protocol including PP and a protocol without PP. Mortality, transfusion requirement and length of hospitalization were extracted and pooled for meta-analysis. Relative risk (RR) and standard mean difference (SMD), along with their confidence intervals (CIs), were used as the pooled statistical indices. Results Eight studies involving 480 patients were identified as being eligible for meta-analysis. PP usage was associated with significantly reduced overall mortality (RR = 0.61, 95% CI = 0.47–0.79, p

Candida auris is a multidrug-resistant human fungal pathogen responsible for nosocomial outbreaks worldwide. Here, the authors identify differential innate immune responses induced by C. auris and Candida albicans in vitro and in vivo, which correlate with structural features of the cell wall.

Pathogenic bacteria pose a devastating threat to public health. However, because of the growing bacterial antibiotic resistance, there is an urgent need to develop alternative antibacterial strategies to the established antibiotics. Herein, iron-doped carbon dots (Fe-CDs, ∼3 nm) nanozymes with excellent photothermal conversion and photoenhanced enzyme-like properties are developed through a facile one-pot pyrolysis approach for synergistic efficient antibacterial therapy and wound healing. In particular, Fe doping endows CDs with photoenhanced peroxidase (POD)-like activity, which lead to the generation of heat and reactive oxygen species (ROS) for Gram-positive and Gram-negative bacteria killing. This study demonstrates Fe-CDs have significant wound healing efficiency of Fe-CDs by preventing infection, promoting fibroblast proliferation, angiogenesis, and collagen deposition. Furthermore, the ultrasmall size of Fe-CDs possesses good biocompatibility favoring clinical translation. We believe that the nanozyme-mediated therapeutic platform presented here is expected to show promising applications in antibacterial.

Introduction The purpose of this study is to assess the efficacy and security of a fixation method for fixing patellar fractures in elderly patients utilizing modified cerclage wire. Methods From January 2015 to December 2020, 31 cases (age≥65 years old) of closed patellar fracture were treated by modified cerclage wiring. Patients in these instances ranged in age from 65 to 87 (73.7 ± 7.2 years), with 15 men and 16 women. 4 instances were type 34-C1 (transverse fracture) according to the AO/OTA classification, 27 cases (87%) were comminuted fractures, including 11 cases that were type 34-C2 (3 fragments), and 16 cases that were type 34-C3 (more than 3 fragments). Postoperative problems such as fragment re-displacement, nonunion, internal fixation loosening, infection, and internal fixation rupture were evaluated. The clinical grading systems of Böstman were used to assess the postoperative clinical outcomes. Results Thirty one patients in all were monitored for 14 to 31 months (22.2 ± 4.5 months). After the procedure, the fracture took 2.5-3.5 months (2.92 ± .25 months) to heal. There were no postoperative issues like infection, dislocation, implant breakage, uncomfortable hardware, or post-traumatic osteoarthritis. According to the clinical grading scales of Böstman, the average score of the final follow-up was 28.6 ± 1.1 (range 26-30). 29 (94%) of the patients had excellent results, whereas just 2 (6%) had good results. The patient’s knee flexion activity ranged from 110 to 140°, making for a favorable prognosis. Conclusion Most patella fractures in the elderly are comminuted. Elderly patients with patellar fractures may be successfully treated with modified cerclage wire, with good results and no noticeable side effects.

Resistance and tolerance are two important strategies employed by the host immune response to defend against pathogens. Multidrug-resistant bacteria affect the resistance mechanisms involved in pathogen clearance. Disease tolerance, defined as the ability to reduce the negative impact of infection on the host, might be a new research direction for the treatment of infections. The lungs are highly susceptible to infections and thus are important for understanding host tolerance and its precise mechanisms. This review focuses on the factors that induce lung disease tolerance, cell and molecular mechanisms involved in tissue damage control, and the relationship between disease tolerance and sepsis immunoparalysis. Understanding the exact mechanism of lung disease tolerance could allow better assessment of the immune status of patients and provide new ideas for the treatment of infections.

Multiple genetic changes in the enteric pathogen Yersinia pseudotuberculosis have driven the emergence of Yesinia pestis, the arthropod-borne, etiological agent of plague. These include developing the capacity for biofilm-dependent blockage of the flea foregut to enable transmission by flea bite. Previously, we showed that pseudogenization of rcsA, encoding a component of the Rcs signalling pathway, is an important evolutionary step facilitating Y. pestis flea-borne transmission. Additionally, rcsD, another important gene in the Rcs system, harbours a frameshift mutation. Here, we demonstrated that this rcsD mutation resulted in production of a small protein composing the C-terminal RcsD histidine-phosphotransferase domain (designated RcsD-Hpt) and full-length RcsD. Genetic analysis revealed that the rcsD frameshift mutation followed the emergence of rcsA pseudogenization. It further altered the canonical Rcs phosphorylation signal cascade, fine-tuning biofilm production to be conducive with retention of the pgm locus in modern lineages of Y. pestis. Taken together, our findings suggest that a frameshift mutation in rcsD is an important evolutionary step that fine-tuned biofilm production to ensure perpetuation of flea-mammal plague transmission cycles.

Although some methods for estimating the instantaneous reproductive number during epidemics have been developed, the existing frameworks usually require information on the distribution of the serial interval and/or additional contact tracing data. However, in the case of outbreaks of emerging infectious diseases with an unknown natural history or undetermined characteristics, the serial interval and/or contact tracing data are often not available, resulting in inaccurate estimates for this quantity. In the present study, a new framework was specifically designed for joint estimates of the instantaneous reproductive number and serial interval. Concretely, a likelihood function for the two quantities was first introduced. Then, the instantaneous reproductive number and the serial interval were modeled parametrically as a function of time using the interpolation method and a known traditional distribution, respectively. Using the Bayesian information criterion and the Markov Chain Monte Carlo method, we ultimately obtained their estimates and distribution. The simulation study revealed that our estimates of the two quantities were consistent with the ground truth. Seven data sets of historical epidemics were considered and further verified the robust performance of our method. Therefore, to some extent, even if we know only the daily incidence, our method can accurately estimate the instantaneous reproductive number and serial interval to provide crucial information for policymakers to design appropriate prevention and control interventions during epidemics.

BackgroundChildren with attention-deficit hyperactivity disorder (ADHD) exhibit executive function deficits, which can be attributed to a dysfunction in the prefrontal region of the brain. Our study aims to evaluate the alteration of brain activity in children with ADHD during the administration of a go/no-go task using functional near-infrared spectroscopy (fNIRS) in comparison to a control group containing typically developing (TD) children.Methods32 children with ADHD and 31 of their TD peers were recruited and asked to perform a go/no-go task while undergoing measurements, with the aim of detecting changes in average oxygenated hemoglobin signaling (Δavg oxy-Hb) via fNIRS in the prefrontal lobe.ResultsfNIRS data showed significant differences between the left and right dorsolateral prefrontal cortices, with a lower Δavg oxy-Hb change in the ADHD group compared to the TD group.ConclusionOur results indicate that brain dysfunction in children with ADHD is related to functional impairments in the dorsolateral prefrontal cortex. The go/no-go task paired with fNIRS represents a useful measurement tool to assess prefrontal brain dysfunction in children struggling with ADHD.

Rationale and Objectives: Based on radiomics signature and clinical data, to develop and verify a radiomics nomogram for preoperative distinguish between benign and malignant of small renal masses (SRM). Materials and Methods: One hundred and fifty-six patients with malignant (n = 92) and benign (n = 64) SRM were divided into the following three categories: category A, typical angiomyolipoma (AML) with visible fat; category B, benign SRM without visible fat, including fat-poor angiomyolipoma (fp-AML), and other rare benign renal tumors; category C, malignant renal tumors. At the same time, one hundred and fifty-six patients included in the study were divided into the training set (n = 108) and test set (n = 48). Respectively from corticomedullary phase (CP), nephrogram phase (NP) and excretory phase (EP) CT images to extract the radiomics features, and the optimal features were screened to establish the logistic regression model and decision tree model, and computed the radiomics score (Rad-score). Demographics and CT findings were evaluated and statistically significant factors were selected to construct a clinical factors model. The radiomics nomogram was established by merging Rad-score and selected clinical factors. The Akaike information criterion (AIC) values and the area under the curve (AUC) were used to compare model discriminant performance, and decision curve analysis (DCA) was used to assess clinical usefulness. Results: Seven, fifteen, nineteen, and seventeen distinguishing features were obtained in the CP, NP, EP, and three-phase joint, respectively, and the logistic regression and decision tree models were built based on this features. In the training set, the logistic regression model works better than the decision tree model for distinguishing categories A and B from category C, with the AUC of CP, NP, EP and three-phase joint were 0.868, 0.906, 0.937 and 0.975, respectively. The radiomics nomogram constructed based on the three-phase joint Rad-score and selected clinical factor performed well on the training set (AUC, 0.988; 95% CI, 0.974-1.000) for differentiation of categories A and B from category C. In the test set, the AUC of clinical factors model, radiomics signature and radiomics nomogram for discriminating categories A and B from category C were 0.814, 0.954 and 0.968, respectively; for the identification of category A from category C, the AUC of the three models were 0.789, 0.979, 0.985, respectively; for discriminating category B from category C, the AUC of the three models were 0.853, 0.915, 0.946, respectively. The radiomics nomogram had better discriminative than the clinical factors model in both training and test sets (P < 0.05). The radiomics nomogram (AIC = 40.222) with the lowest AIC value was considered the best model compared with that of the clinical factors model (AIC = 106.814) and the radiomics signature (AIC = 44.224). The DCA showed that the radiomics nomogram have better clinical utility than the clinical factors model and radiomics signature. Conclusions: The logistic regression model has better discriminative performance than the decision tree model, and the radiomics nomogram based on Rad-score of three-phase joint and clinical factors has a good predictive effect in differentiating benign from malignant of SRM, which may help clinicians develop accurate and individualized treatment strategies.

Abstract Background Coxiella burnetii (Cb) is the causative agent of the zoonotic disease Q fever which is distributed worldwide. Molecular typing of Cb strains is essential to find out the infectious source and prevent Q fever outbreaks, but there has been a lack of typing data for Cb strains in China. The aim of this study was to investigate the genotypes of Cb strains in wild rats in Yunnan Province, China. Results Eighty-six wild rats (Rattus flavipectus) were collected in Yunnan Province and 8 of the 86 liver samples from the wild rats were positive in Cb-specific quantitative PCR (qPCR). The Cb strains from the 8 rats were then typed into 3 genotypes using 10-spacer multispacer sequence typing (MST), and 2 of the 3 genotypes were recognized as novel ones. Moreover, the Cb strains in the wild rats were all identified as genotype 1 using 6-loci multilocus variable number of tandem repeat analysis (MLVA). Conclusions This is the first report of genotypic diversity of Cb strains from wild rats in China. Further studies are needed to explore the presence of more genotypes and to associate the genotypes circulating in the wildlife-livestock interaction with those causing human disease to further expand on the epidemiological aspects of the pathogen.

The vagina contains at least a billion microbial cells, dominated by lactobacilli. Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age, as well as cervical, fecal, and salivary samples from a second cohort of 632 women. Factors such as pregnancy history, delivery history, cesarean section, and breastfeeding were all more important than menstrual cycle in shaping the microbiome, and such information would be necessary before trying to interpret differences between vagino-cervical microbiome data. Greater proportion of Bifidobacterium breve was seen with older age at sexual debut. The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history. Potential markers for lack of menstrual regularity, heavy flow, dysmenorrhea, and contraceptives were also identified. Lactobacilli were rare during breastfeeding or post-menopause. Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome. Gut and salivary microbiomes, plasma vitamins, metals, amino acids, and hormones showed associations with the vagino-cervical microbiome. Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Klebsiella pneumoniae (K. pneumoniae) is an important pathogen that can cause severe hospital- and community-acquired infections. To systematically investigate its methylation features, we determined the whole-genome sequences of 14 K. pneumoniae strains covering varying serotypes, multilocus sequence types, clonal groups, viscosity/virulence, and drug resistance. Their methylomes were further characterized using Pacific Biosciences single-molecule real-time and bisulfite technologies. We identified 15 methylation motifs [13 N6-methyladenine (6mA) and two 5-methylcytosine (5mC) motifs], among which eight were novel. Their corresponding DNA methyltransferases were also validated. Additionally, we analyzed the genomic distribution of GATC and CCWGG methylation motifs shared by all strains, and identified differential distribution patterns of some hemi-/un-methylated GATC motifs, which tend to be located within intergenic regions (IGRs). Specifically, we characterized the in vivo methylation kinetics at single-base resolution on a genome-wide scale by simulating the dynamic processes of replication-mediated passive demethylation and MTase-catalyzed re-methylation. The slow methylation of the GATC motifs in the replication origin (oriC) regions and IGRs implicates the epigenetic regulation of replication initiation and transcription. Our findings illustrate the first comprehensive dynamic methylome map of K. pneumoniae at single-base resolution, and provide a useful reference to better understand epigenetic regulation in this and other bacterial species.