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‍Objective‍ ‍To explore the effect and preliminary mechanism of the plant-derived immunostimulatory molecule, ophiopogonin, on enhancing the immune response of a subunit vaccine with the receptor-binding domain (RBD) of coronavirus spike protein as the antigen. Methods‍ ‍CCK-8 assay was used to determine the cytotoxicity of ophiopogonin D' (OPD') on bone marrow-derived dendritic cells (BMDCs). Female Balb/c mice were randomly divided into RBD, RBD/OPD', RBD/Alum, and control groups. The immunization dose was 5 μg of antigen per mouse and 100 μg of adjuvant per mouse, and immunization was carried out according to the intramuscular injection immunization procedure on days 0, 21, and 42. The titers of specific IgG and its subtype antibodies were detected by ELISA. The cytokine levels in the supernatant of splenocytes were detected using ELISA. The number of splenocytes secreting IFN-γ was detected by ELISpot. Laser confocal microscopy was employed to observe the uptake of antigen by BMDCs. The phagocytic ability of BMDCs for antigen was quantitatively analyzed by flow cytometry. The mechanism of its enhanced immune effect was preliminarily explored using transcriptomics technology combined with bioinformatics research. Results‍ ‍When the concentration of OPD' was less than 5 μg/mL, the survival rate of BMDCs was 100%. After a single intramuscular injection in mice, except for a slight decrease in body weight, the other biochemical indicators were within corresponding normal ranges. After intramuscular injection immunization of the vaccine, the titers of serum-specific IgG, IgG1, and IgG2a in the RBD/OPD' group were significantly higher than those in the RBD group (P

［Objective］ The grid-side converter is a core electrical component in high-speed railway EMU traction drive system, and its reliability is directly related to the safe operation of the train. Therefore, it is essential to simulate and analyze the temperature rise characteristics of the grid-side converter in high-speed EMU to explore the relationship between temperature rise, operating conditions, and environmental factors, providing theoretical support for temperature evaluation during actual train operation. ［Method］ The temperature rise characteristics of power devices are examined, and an electrothermal simulation model is established incorporating the power loss model and thermal network model. The former is used to quantify the losses of power devices under different operating conditions, while the latter simulates internal heat conduction and dissipation processes of power devices considering the train′s operating environment. The simulation accounts for multiple influencing factors such as operating conditions and ambient temperature, dynamically analyzing the temperature variation trends of power devices and their impact on converter performance. ［Result & Conclusion］ Simulation results demonstrate that the established electrothermal simulation model accurately reflects the temperature rise characteristics of power devices. This research provides critical data support for evaluating temperature changes in grid-side converters during actual train operation.

ObjectivesThe helium cooling tube is the core component of the fusion superconducting magnet system. It connects the superconducting magnet cooling channel and the cryogenic system, and is directly related to the operation stability of the superconducting magnet system. Since helium cooling pipes need to be welded on site, the structural design of helium pipes needs to be comprehensively considered from multiple aspects such as functional realization and on-site process operability, and reasonable solutions need to be proposed.MethodsThrough comprehensive analysis of the polar field structure of the fusion reactor, the structural optimization and pressure loss assessment of the cryogenic helium cooling tube were carried out. A comprehensive comparative analysis of the helium hole size and the optimal design of weld chamfer was carried out from the perspective of structural mechanics. The general requirements for the design criteria of the fusion reactor magnet helium cooling tube were proposed. Based on the structural mechanical analysis and pressure loss analysis of helium cooling tubes, and the comprehensive consideration of field operability, a helium cooling tube design scheme was proposed to meet the requirements of helium cooling tubes for fusion reactor magnets.ResultsAlthough short running helium cooling pipes will cause an increase in local pressure loss, which is equivalent to a conductor of 2.7 meters long, the pressure loss caused by them is basically negligible compared with the total length of the coil.ConclusionsThe adoption of the short track helium tube design scheme can not only meet the functional requirements, but also greatly improve the operability of the field process and meet the requirements of helium cooling tubes for superconducting magnets in fusion reactors.

AIM: To explore the predictive value of the combination of triglyceride-glucose(TyG)index, nesfatin-1, and retinol-binding protein 4(RBP4)for diabetic retinopathy, and provide evidence for early prediction of DR.METHODS: The clinical data of 164 patients with type 2 diabetes mellitus(T2DM)who admitted to the hospital between February 2022 and December 2023 were retrospectively collected. Based on the fundus examination results, these patients were divided into two groups: the DR group(n=43), including proliferative DR(PDR, n=19)and non-proliferative DR(NPDR, n=24), and the T2DM without DR group(n=121). The TyG index and the level of nesfatin-1 and RBP4 were measured after admission.RESULTS:T2DM patients with DR had a longer disease duration compared with T2DM patients without DR, and the DR group had higher fasting blood glucose, glycosylated hemoglobin, triglyceride, total cholesterol, low-density lipoprotein, TyG index, and RBP4 levels, while lower high-density lipoprotein and nesfatin-1 levels(all P

Abstract The global health crisis of antibacterial resistance (ABR) poses a particular threat in low-resource settings like East Africa. Interventions for ABR typically target antibiotic use, overlooking the wider set of factors which drive vulnerability and behaviours. In this cross-sectional study, we investigated the joint contribution of behavioural, environmental, socioeconomic, and demographic factors associated with higher risk of multi-drug resistant urinary tract infections (MDR UTIs) in Kenya, Tanzania, and Uganda. We sampled outpatients with UTI symptoms in healthcare facilities and linked their microbiology data with patient, household and community level data. Using bivariate statistics and Bayesian profile regression on a sample of 1610 individuals, we show that individuals with higher risk of MDR UTIs were more likely to have compound and interrelated social and environmental disadvantages: they were on average older, with lower education, had more chronic illness, lived in resource-deprived households, more likely to have contact with animals, and human or animal waste. This suggests that interventions to tackle ABR need to take account of intersectional socio-environmental disadvantage as a priority.

BackgroundRecently, weight-adjusted-waist index (WWI), a new index for evaluating obesity, has been developed. This study aimed to examine the association between WWI and T2DM in Chinese urban adults.MethodA total of 5,0978 eligible participants drawn from the prospective REACTION study (Cancer Risk Assessment in Chinese People with Diabetes) were included in this study. Participants were divided into 3 groups based on baseline WWI levels. Pearson correlation analysis and binary logistic regression analysis were conducted to explore the association of WWI with T2DM risk factors and with T2DM risk.ResultsThe prevalence of obesity, central obesity and T2DM was 14.2%, 46.8% and 11.0% respectively, with a median age of 57 years. Logistic analysis showed that the WWI was significantly associated with the risk of T2DM. Compared to the lowest tertile of WWI (T1) serving as the reference group, the second tertile (T2) and the third tertile (T3) were associated with a 0.218-fold [1.218 (1.152, 1.288), P

Purpose The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value.Methods Data of two cohorts were retrospectively collected from consecutive patients who underwent primary pancreatic resection from January 2015 to December 2017. We used tumor specimens to screen out the most suitable markers for the spatial distribution analysis for CAFs subpopulations. We utilized a tissue microarray to assess the spatial intensity of α-SMA expression within the tumor microenvironment. Specifically, we classified CAFs into two types based on their α-SMA spatial expression. Type II CAFs were designated as those located in the juxtatumoural stroma with α-SMA expression that was moderate or higher, and those in the peripheral stroma with α-SMA expression that was less than moderate. All other cases, where the α-SMA expression did not meet these criteria, were categorized as Type I CAFs. Multivariable Cox proportional hazards regression was used to assess risk factors associated with patient outcomes. RNA sequencing data were obtained from bulk tumor samples and isolated CAFs from patients to reveal the distinct pattern and elucidated their fundamental characteristics.Results The α-SMA spatial intensity was the most suitable variable for representative of CAFs spatial characteristics. Patients with Type Ⅰ CAFs were more likely to be allocated into N1 or N2 of the N stage and Ⅱ and Ⅲ of the TNM stage. The spatial distribution pattern of CAFs (Type Ⅰ v.s. Type Ⅱ: HR, 1.568; 95 % CI, 1.053–2.334; P = 0.027) was an independent prognostic factor in the discovery cohort, so as in the validation (Type Ⅰ vs. Type Ⅱ: HR, 2.197; 95 % CI, 1.410–3.422; P = 0.001). RNA sequencing analysis revealed that the differentially expressed genes (DEGs) in Type I CAFs are closely associated with those in corresponding tumor tissues, highlighting the enhanced biological significance of immune-related and oncogenic invasive pathways.Conclusions Our findings that two types of α-SMA-positive CAFs with different spatial patterns present heterogeneously across tissues of PDACs and correlated with patients’ outcomes. The spatial location of CAFs may facilitate patients’ selection in precision medicine of PDACs.

Approximately one-fifth of surgeries performed at major cancer centres worldwide are palliative in nature, and one-third of advanced cancer patients receive surgery during their last year of life.1,2 Serious illness communication (SIC) is an essential component of palliative care. In the context of palliative surgical oncology, the surgical team will facilitate a shared decision-making with patients who are considered for high-risk palliative surgery or other interventions. This explores the goals of surgery or other proposed interventions and the prognosis; it also clarifies code status, assesses for suitability for hospice care, and explains the associated risks of surgical morbidity and mortality for the advanced cancer patients and their families.3

Abstract Background SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB.

A middle-aged male came to Peking Union Medical College Hospital for treatment because of "pain for 10+ years, aggravated with emotional instability for 5 years". The patient's pain had a huge impact on life, with poor results even after repeated diagnosis and treatment in other hospitals. After multi-disciplinary discussion, it had been clarified that the pain was mainly caused by gout. The disease was heavily influenced by psychosocial factors. Therefore, the patient fits the diagnosis of "Psychological and Behavioral Factors Affecting Physical Diseases". The multi-disciplinary comprehensive management of the patient was carried out to identify and treat psychological factors affecting other medical conditions. After this mental treatment was performed, the patient's conditions significantly improved. The diagnosis and treatment of this patient demonstrates the importance of the multi-disciplinary treatment team for somatic symptoms (disorders).

Abstract [Objective] Exploring the effects of suitable concentrations of indole butyric acid (IBA) on rooting and sprouting as well as on antioxidant property and gene expression related to growth hormone biosynthesis pathway of fig(Ficus carica L.) cuttings may provide theoretical basis for its application in fig breeding, propagation, promotion, and planting. [Methods] The hard branches of ‘Bojihong’ fig variety were used as cuttings to analyze the effects of IBA treatments (0, 30, 45, 60, 90 mg/L) on the rooting traits and antioxidant properties of the scions, as well as analyzed the transcriptome of axillary buds in the middle part of fig cuttings under 45 mg/L IBA treatment. [Results] (1) The germination and rooting rates of fig spikes reached the maximum at 45 mg/L IBA and differed from other treatments and the control.(2) With the increase of IBA concentrations, the SOD and CAT activities of spikes showed a trend of first decreasing and then increasing, and both were lower than the control at 45 and 60 mg/L IBA, while POD activity was unchanged between the treatment and control. MDA and H2O2 contents in the spikes under IBA treatments were higher than the control, and MDA content in the spikes at 45 mg/L IBA was lower than other treatments. (3) Transcriptome analysis showed that there were 6 879 differentially expressed genes at 45 mg/L IBA. KEGG enrichment showed that there were 10 differential pathways. GO enrichment analysis indicated that the biological processes and molecular functions were the main biological pathways; the genes related to CAT and SOD were enriched in peroxisomal pathway, while the genes related to POD were enriched in phenylpropane biosynthetic pathway. The metabolism-related gene FcGH3 was up-regulated in the IAA biosynthesis pathway, and the genes related to signaling, such as FcAUX1, FcARG7, and FcARF, were down-regulated. [Conclusion] IBA treatment induced the expression of genes encoding antioxidant enzymes and genes involved in IAA biosynthesis pathway of fig spikes, enhanced resistance to stress, and promoted rooting, sprouting, and seedling formation and 45 mg/L IBA had the best effect

The mechanical properties and failure characteristics of joined rocks have an important impact on the disaster prevention of underground engineering and the sustainable development of mineral resources. The effects of confining pressure, joint location, and joint thickness on the mechanical properties of rock-like specimens under triaxial test have been studied. Furthermore, using the "DFN-age" function of PFC numerical simulation, the stress characteristics, and failure characteristics of rock specimens under different confining pressure, joint location and joint thickness are analyzed. The research results indicate that as the thickness of the joint increases and the joint position approaches the center of the specimen, the compressive strength of the specimen decreases. As the confining pressure increases, the compressive strength increases and failure modes of rock like specimens with different joint types also tend to be similar. The specimens manifest complex shear-tensile composite failures. In addition, the initiation cracks and main control cracks at the joint terminus can be classified as reverse tensile wing cracks, reverse shear cracks, shear cracks and tensile wing cracks. When the joint thickness of the specimen is 1.0 mm and the distance from the joint position to the center of the specimen is 10–20 mm, the crack evolution characteristics and stress distribution law of the specimen will undergo a transformation.

Anti-PD-1 antibody therapy has achieved success in tumor treatment; however, the duration of its clinical benefits are typically short. The functional state of intratumoral CD8+ T cells substantially affects the efficacy of anti-PD-1 antibody therapy. Understanding how intratumoral CD8+ T cells change will contribute to the improvement in anti-PD-1 antibody therapy. In this study, we found that tumor growth was not arrested after the late administration of anti-PD-1 antibody and that the antitumor function of CD8+ T cells decreased with tumor progression. The results of the RNA sequencing of CD8+ T cells infiltrating the tumor site on days 7 and 14 showed that the cell adhesion molecule Lymphocyte Function-associated Antigen-1 (LFA-1) participates in regulating the antitumor function of CD8+ T cells and that decreased LFA-1 expression in intratumoral CD8+ T cells is associated with tumor progression. By analyzing the Gene Expression Omnibus (GEO) database and our results, we found that the antitumor function of intratumoral CD8+ T cells with high LFA-1 expression was stronger. The formation of immune synapses is impaired in Itgal-si CD8+ T cells, resulting in decreased anti-tumor function. LFA-1 expression in intratumoral CD8+ T cells is regulated by the IL-2/STAT5 pathway. The combination of IL-2 and anti-PD-1 antibody effectively enhanced LFA-1 expression and the antitumor function of intratumoral CD8+ T cells. The adoptive transfer of OT-1 T cells overexpressing LFA-1, STAT5A, or STAT5B resulted in higher antitumor function, deferred tumor growth, and prolonged survival. These findings indicate that LFA-1-mediated immune synapse acts as a regulator of the antitumor function of intratumoral CD8+ T cells, which can be applied to improve anti-PD-1 antibody therapy.

Harvesting environmental energy sources is crucial for achieving renewable energy generation and net-zero emissions. However, ensuring uninterrupted electricity generation from environmental energy sources remains challenging. In this study, we present a simple, compact, and expandable all-day vertical passive thermoelectric generator (V-TEG) with a double-sided reflective structure that simultaneously harnesses solar and space cold energy. Outdoor experimental measurements, combined with finite element simulation analysis, revealed that the optimal angles of the solar reflector relative to the TEG range from 30° to 50°. Additionally, the TEG placed in the north–south orientation was found to enhance its daytime performance. The use of low-cost black paint combined with the solar reflector achieved equivalent spectral selectivity, effectively minimizing the infrared heat loss of the hot end of the TEG. During a 48-h outdoor test, the V-TEG achieved an average daytime power of 112.00 mW/m2 and a peak of 363.42 mW/m2. Comparative experiments demonstrated that the V-TEG outperformed horizontally placed TEG during the daytime. Furthermore, scaling the system by connecting three TEGs in series significantly increased the daily power output. This compact V- TEG system offers a promising solution for long-term power generation in low-power sensors and off-grid communities, supporting renewable energy and carbon neutrality goals.

Thermoelectric generators (TEGs) integrated with solar energy and radiative cooling offer a promising approach for generating power. Concentrated solar energy enhances generation by increasing the solar flux density. However, the relationship between thermoelectric generation and concentration ratio remains not well understood. In this study, the finite element method is employed to investigate the temperature difference across TEGs and the change in generation performance with varying concentration ratios. The results show that due to the mismatch among cooling, heating, and parasitic heat conduction powers, the optimal power generation does not occur at the maximum concentration ratio. As the concentration ratio increases, the temperature difference across the single TEG and its output power initially increase and then decrease. To further improve the power generation performance at high concentration ratios, this study introduces TEG stacking strategy to enhance waste heat recovery by increasing thermal resistance. Outdoor experiments with self-made solar absorptive coating and radiative cooling coating validate this approach, achieving a temperature difference of 64.17 °C and a power density of 135.57 W m−2 by stacking three TEGs, outperforming a single TEG by over three times. This study offers a potential method to continuously power remote off-grid communities and low-power devices.

The impact of civil engineering course education on civil engineers is profound and crucial. Due to the hierarchical and ambiguous nature of quality assessment for flipped classroom teaching, there is an urgent demand for a rational and effective approach to conduct such assessments. This would enable the targeted formulation of instructional improvement methods based on assessment outcomes, ultimately elevating the quality of pedagogy. This study combines the analytic hierarchy process and fuzzy evaluation method. The fuzzy evaluation method is utilized to identify four primary evaluation factor sets, fourteen secondary judgment factor sets, and five evaluation outcome sets, with subsequent quantification of the assessment results. The analytic hierarchy process is employed to ascertain the weight coefficients of the evaluation factors. The comprehensive assessment model for flipped classroom teaching quality is established. The assessment results indicate that the overall quality of flipped classroom teaching in the civil engineering major at Anhui University of Science and Technology, conducted through the platform of Superstar Learning Hub, falls within the ‘Good’ category. The fuzzy comprehensive evaluation score for extracurricular learning quality is the lowest, and the weight proportion attributed to flipped classroom infrastructure is the highest. Consequently, several targeted improvement measures are proposed to enhance the quality of flipped classroom teaching.

Abstract Background Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection. Methods One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19–9 (CA19-9) was explored to improve model performance. Results The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved. Conclusions Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.

Scaffold materials, seed cells and growth factors are referred to as the three elements of bone tissue engineering (BTE). However, the physical properties and biocompatibility of these scaffolds and the safety and cost of their growth factors limit their clinical application. Therefore, it is critical to develop a novel scaffold modified with efficient growth factors that meets the requirements of BTE. Herein, 3D-printed poly (lactic-co-glycolic acid)/hydroxyapatite (PLGA/HA) composite scaffolds modified with new fusion peptides, which can effectively promote the regeneration and repair of bone defects, were developed. 3D-printed PLGA/HA composite scaffolds with appropriate HA contents were prepared and had appropriate mechanical properties. In addition, the surface of the 3D-printed PLGA/HA composite scaffold was modified with new fusion peptides to provide osteogenic, antimicrobial, and angiogenesis-promoting effects. In vitro experiments showed that the fusion peptide-modified scaffolds had good biocompatibility and a certain degree of antibacterial activity. Moreover, the fusion peptide-modified scaffolds significantly improved the migration ability of BMSCs and Ea.hy926 cells, promoted the expression of osteogenesis-related factors (BMP2, RUNX2, ALP, OPN) in BMSCs, and promoted the expression of angiogenesis-related factors (VEGF and HIF-1α) in Ea.hy926 cells. In vivo experiments showed that the fusion peptide-modified scaffolds had good osteogenic ability. This study reveals considerable application potential for bone defect repair and provides a new option of scaffold material for BTE.

Local data are essential for the analysis of abrupt conditions in traffic flow. In this research, we address the shortcomings of real-time traffic flow detection data, which inadequately represent the density characteristics of vehicular traffic. To mitigate this issue, we establish mathematical relationships among traffic flow density, time headway, and vehicle speed, based on the fundamental characteristics of traffic flow dynamics. This framework allows for the estimation of density across various road segments. Recognizing the nonlinear dynamics that characterize traffic flow, we introduce a microscopic traffic flow cusp catastrophe potential function that incorporates headway, utilizing cusp catastrophe theory alongside microscopic traffic flow parameters to analyze real-time variations in traffic flow potential characteristics. In the experimental section, we developed fitting regression functions for traffic flow parameters using road detection data from the cities of Nanjing and Yueyang in China. We also compared outcomes derived from the theoretical model with the parameter estimation results obtained from the data, which facilitated the calculation of traffic flow characteristics, such as cusp density and volume over a one-month period. The results derived from the proposed potential function exhibit the functions’ greater capacity to capture the complex fluctuations in traffic flow compared to traditional traffic potential functions, thereby providing a valuable instrument with which to evaluate traffic flow characteristics in conjunction with real-time monitoring data.

The World Health Organization (WHO) “Global Tuberculosis Report 2024” underscores the ongoing challenges and progress in the global fight against tuberculosis (TB). Despite a slowdown in the annual increase in TB cases and a decline in TB-related deaths, the disease remains a significant public health threat with 10.8 million new cases reported in 2023. The report reveals a persistently high burden of TB, especially in low- and middle-income countries, and highlights the escalating issue of drug-resistant TB. The report also emphasizes the critical need for increased funding, improved diagnostics, and more effective TB treatment regimens. The impact of the COVID-19 pandemic on TB control has been substantial, disrupting healthcare services and exacerbating existing challenges. This paper provides an in-depth interpretation of the report, analyzes global TB trends, updates the status of drug-resistant TB, discusses the intersection between TB and HIV, and summarizes the implications of the pandemic on TB control efforts. The report concludes with a call for intensified global action, including increased investment in research and innovation, to achieve the United Nations’ Sustainable Development Goals related to TB control. The stakes are high, but with concerted efforts, the goal of ending the TB epidemic is within reach.

IntroductionWe investigated the efficacy and safety of oral sodium bicarbonate in kidney-transplant recipients and non-transplant patients with chronic kidney disease (CKD), which are currently unclear.MethodsPubMed, Cochrane Library, Embase, and Web of Science were searched for randomized controlled trials investigating the efficacy and safety of sodium bicarbonate versus placebo or standard treatment in kidney-transplant and non-transplant patients with CKD.ResultsSixteen studies of kidney-transplant recipients (two studies, 280 patients) and non-transplant patients with CKD (14 studies, 1,380 patients) were included. With non-transplant patients, sodium bicarbonate slowed kidney-function declines (standardized mean difference [SMD]: 0.49, 95% confidence interval [CI]: 0.14–0.85, p = 0.006) within ≥12 months (SMD: 0.75 [95% CI: 0.12–1.38], p = 0.02), baseline-serum bicarbonate

Abstract Introduction Receptor-interacting protein kinase 1 (RIPK1), a key mediator of inflammation through necroptosis and proinflammatory cytokine production, may play a role in the pathogenesis of immune-mediated inflammatory diseases such as chronic plaque psoriasis. An experimental medicine study of RIPK1 inhibition with GSK2982772 immediate-release formulation at doses up to 60 mg three times daily in mild to moderate plaque psoriasis indicated that efficacy may be improved with higher trough concentrations of GSK2982772. Methods This multicenter, randomized, double-blind, placebo-controlled, repeat-dose study (NCT04316585) assessed the efficacy, safety, pharmacokinetics, and pharmacodynamics of 960 mg GSK2982772 (once-daily modified-release formulation) in patients with moderate to severe plaque psoriasis. Twenty-nine patients were randomized 2:1 to GSK2982772 (N = 19) or placebo (N = 10) for 12 weeks. Results GSK2982772 was well tolerated with trough concentrations greater than tenfold higher than the previous phase 1 study with immediate release. Despite near complete RIPK1 target engagement in blood and modest reduction in circulating inflammatory cytokines, the proportion of patients achieving 75% improvement from baseline in Psoriasis Area Severity Index score at week 12 was similar between GSK2982772 and placebo (posterior median 1.8% vs 4.9%, respectively), with an estimated median treatment difference of − 2.3%. This analysis incorporated historical placebo data through the use of an informative prior distribution on the placebo arm. Week 4 changes in skin biopsy gene expression suggested sufficient local drug exposure to elicit a pharmacodynamic response. Conclusion Administration of the RIPK1 inhibitor GSK2982772 to patients with moderate to severe plaque psoriasis did not translate into meaningful clinical improvements.

Abstract Severe tissue injuries pose a significant risk to human health. Conventional wound dressings fall short in achieving effective tissue regeneration, resulting in suboptimal postoperative healing outcomes. In this study, an asymmetric adhesive wound dressing (marked as SIS/PAA/LAP) was developed, originating from acrylate acid (AA) solution with laponite (LAP) nanoparticles polymerization and photo-crosslinked on the decellularized extracellular matrix small intestinal submucosa (SIS) patch. Extensive studies demonstrated that the SIS/PAA/LAP exhibited higher tissue adhesion strength (~ 33 kPa) and burst strength (~ 22 kPa) compared to conventional wound dressings like Tegaderm and tissue adhesive products. Importantly, it maintained favorable cell viability and demonstrated robust angiogenic capacity. In animal models of full-thickness skin injuries in rats and skin injuries in Bama miniature pigs, the SIS/PAA/LAP could be precisely applied to wound sites. By accelerating the formation of tissue vascularization, it displayed superior tissue repair outcomes. This asymmetrically adhesive SIS-based patch would hold promising applications in the field of wound dressings.

The probability of seismic pounding of sliding isolation liquid storage tank (LST) is high. Considering normal impact force and tangential friction force at the location of pounding under bidirectional earthquake, a 3D calculation model of sliding isolation LST is established based on a finite element method. Pounding dynamic responses under unidirectional and bidirectional earthquakes are comparatively investigated, and frequency domain analysis is also conducted. Finally, mitigation measure for adverse effect caused by the pounding is proposed. Results show that the influence of concrete nonlinearity on the pounding is very significant. Dynamic responses are significantly increased due to the pounding, and the maximum tensile stress of tank wall reaches 2.510 MPa under ChiChi earthquake, which exceeds the concrete tensile strength. Besides, pounding causes a high-frequency response. A reasonable rubber cushion design can ensure that the maximum displacement of the sliding isolation LST is limited by the moat wall, and the failure probability caused by the pounding is decreased.

Elevated serum uric acid (UA) level is related to type 2 diabetic retinopathy (DR). Vascular endothelial growth factor (VEGF), high-sensitivity C-reactive protein (hs-CRP), and cystatin C (Cys-C) have involvement in type 2 DR complicated with hyperuricemia (HUA) (HUDR), and we explored their clinical values in HUDR. Type 2 DR patients were allocated into HUDR/DR groups, with type 2 diabetes mellitus (T2DM) patients as the control group. Serum VEGF and inflammation markers hs-CRP, and Cys-C levels were assessed by ELISA and immunoturbidimetry. The correlations between serum UA level and VEGF/hs-CRP/Cys-C were analyzed by Pearson tests, diagnostic values of VEGF/hs-CRP/Cys-C were analyzed by receiver operating characteristic curves, and the independent risk factors in HUDR were analyzed by logistic multivariate regression. Serum VEGF/hs-CRP/Cys-C level differences among the T2DM/DR/HUDR groups were statistically significant, with the levels in HUDR > DR > T2DM. Serum UA level in HUDR patients was positively correlated with serum VEGF/hs-CRP/Cys-C. Serum VEGF/hs-CRP/Cys-C assisted in HUDR diagnosis, with their combination showing the greatest diagnostic value. UA/FPG/HbA1C/VEGF/hs-CRP/Cys-C were independent risk factors for HUDR. The incidence of proliferative DR was increased in HUDR patients. Collectively, serum VEGF, hs-CRP, and Cys-C levels in HUDR patients were increased, and HUA might promote DR progression.

Liquid storage tank is widely used in the petrochemical industry, earthquake will lead to structural damage and secondary disasters, and damping control opens up a new way for seismic design of liquid storage tank. Considering soil-structure-fluid interaction, liquid sloshing dynamic behavior and material nonlinearity, a three-dimensional calculation model of shock absorption liquid storage tank is established by combining sliding isolation and displacement-limiting devices. The dynamic responses of the liquid storage tanks under the action of Kobe and El-Centro waves are investigated, and the influence of soil-structure interaction (SSI) on the dynamic response is discussed. The results show that the damping ratio is basically between 30% and 90%. After the SSI is considered, the damping ratio of liquid sloshing wave height is increased, while the damping ratio of the dynamic response of the liquid storage tank is decreased, and the change of elastic modulus has little effect on the damping effect. The sliding isolation with displacement-limiting devices has significant damping control effects on the liquid sloshing wave height and the dynamic responses of the liquid storage tank.

The research on deformation zoning mechanism of tunnel surrounding rock is of great significance for ensuring safe production and disaster prevention in coal mines. However, the traditional deformation zoning theory of tunnel surrounding rock uses the ideal strain softening model as the criterion for judging the zoning type of all tunnel surrounding rock, ignoring the difference between the deformation zoning type of a specific actual tunnel and the basic zoning type of surrounding rock. In order to study the method for determining the actual deformation zoning type of tunnel surrounding rock, the formation mechanism of the actual deformation zoning of tunnel surrounding rock has been revealed. Combined with engineering examples, a method for determining the actual deformation zoning type and boundary stress of specific tunnel surrounding rock has been proposed. The results show that the boundary stress and position of the actual deformation zone are determined by the peak strength fitting line, residual strength fitting line, support strength line, and the position of the circumferential and radial stress relationship lines of each deformation zone. The actual boundary stress of each zone of tunnel surrounding rock is ultimately only related to the basic mechanical properties of the tunnel surrounding rock and the in-situ stress field. The research results can provide reference for disaster management of underground engineering, stability evaluation of surrounding rock, and support scheme design.

AbstractContext Diabetic nephropathy (DN) is the main cause of end-stage renal disease. Modified Shen-Yan-Fang-Shuai formula (M-SYFSF) has excellent clinical efficacy in treating diabetic kidney disease. However, the potential mechanism of M-SYFSF remains unknown.Objective To investigate the mechanism of M-SYFSF against DN by network pharmacological analysis and biological experiments.Materials and methods Utilizing a web-based pharmacology database, the potential mechanisms of M-SYFSF against DN were identified. In vivo experiments, male SD rats were injected with streptozotocin (50 mg/kg) and got uninephrectomy to construct a model of DN. M-SYFSF (11.34 g/kg/d) was gavaged once per day for 12 weeks after model establishment. In vitro experiments, human proximal tubular cells (HK-2) were performed with advanced glycation end-products (AGEs) (100 μg/mL), then intervened with M-SYFSF freeze-dried powder. Pathological staining, WB, IHC, ELISA were conducted to explore the mechanism of M-SYFSF against DN.Results Network pharmacological analysis showed that MAPK pathway was the potential pathway. Results showed that compared with the Model group, M-SYFSF significantly reduced 24h urine albumin, UACR, and serum creatinine levels (54.90 ± 26.67 vs. 111.78 ± 4.28, 8.87 ± 1.69 vs. 53.94 ± 16.01, 11.56 ± 1.70 vs. 118.70 ± 49.57, respectively), and improved renal pathological changes. Furthermore, the intervention of M-SYFSF reduced the expression of pro-inflammatory cytokines and inhibited the activation of MAPK pathway in AGEs-treated HK-2 cells.Discussion and conclusion M-SYFSF is likely to reduce inflammation in DN by inhibiting the MAPK pathway. It provides a theoretical basis for the clinical application of M-SYFSF in the treatment of DN.

The application of meshes in surgery is severely limited by complications associated with the non-absorbable nature, the lack of bioactivities, and the need of sutures and/or staples to fix meshes on tissues. In this contribution, a self-adhesive hydrogel-mesh composite (HMC) with biodegradability and multiple bioactivities was developed to address these issues and meet the clinical requirements. In this HMC system, GelMA hydrogel network was first macrotopological entangled with the fibers of a natural small intestinal submucosa (SIS) meshes, and then strengthened by soaking in a multi-functional H-bond provider (i.e., tannic acid, TA) solution to form the G/SIS-TA composite. The pyrogallol groups of the TA molecules endow G/SIS-TA with excellent wet adhesiveness (shear strength: ∼60 kPa), antioxidant, and antibacterial ability. The G/SIS-TA was also found to exhibit excellent biodegradability, biocompatibility, and immunoregulatory activity. The G/SIS-TA significantly decrease the bacterial burden in a mouse peritonitis infection model and promote the healing of infected full-thickness rat skin wounds in vivo. This work not only reports a novel SIS-based HMC which was efficient in treating infected wounds, but also offers an innovative strategy of the development of self-adhesive bio-patch for various biomedical applications.

IntroductionTimely palliative care and surgical interventions improve symptoms, health-related quality of life (HRQoL), and reduce medical cost for seriously ill adults at end of life (EOL). However, there is still poor delivery and underutilization of these palliative services. We hypothesize that the sub-optimal delivery is due to limited understanding among healthcare providers.MethodsA nationwide cross-sectional online survey was conducted among primary and tertiary healthcare providers. The survey assessed challenges faced, palliative education, confidence in managing palliative patients, and knowledge on palliative surgery. Overall palliative care awareness and knowledge was assessed using a 6-point score. Likelihood of considering various palliative interventions at EOL was also determined using a threshold score (higher score = higher threshold).ResultsThere were 145 healthcare providers who completed the survey (81.9% response rate); majority reported significant challenges in providing various aspects of palliative care: 57% (n = 82) in the provision of emotional support. Sixty-nine percent (n = 97) in managing social issues, and 71% (n = 103) in managing family expectations. Most expressed inadequate palliative care training in both under-graduate and post-graduate training and lack confidence in managing EOL issues. Up to 57% had misconceptions regarding potential benefits, morbidity and mortality after palliative surgery. In general, most providers had high thresholds for Intensive Care Unit admissions and palliative surgery, and were more likely to recommend endoscopic or interventional radiology procedures at EOL.ConclusionHealthcare providers in Singapore have poor knowledge and misconceptions about palliative care and surgery. Improving awareness and education among those caring for seriously ill adults is essential.

Background and purpose: Diffuse large B-cell lymphoma/high-grade B-cell lymphoma (DLBCL/HGBL) with gene rearrangement of MYC, BCL2 and BCL6, also known as triple-hit lymphoma (THL), has a low incidence and relevant literature is limited. Thus comprehensive and sufficient understanding is lacking. The purpose of this study was to explore the clinicopathological features and prognosis of this rare disease. Methods: Ten cases of THL diagnosed in Department of Pathology, Fudan University Shanghai Cancer Center from June 2016 to December 2021 were collected. Clinical features were analyzed retrospectively. Histopathological features were observed using H-E stain. Immunophenotype was analyzed by immunohistochemistry. The rearrangement of MYC, BCL2 and BCL6 genes was detected by fluorescence in situ hybridization (FISH), and Epstein-Barr virus (EBV) infection was detected by in situ hybridization using EBV-encoded RNA (EBER). Results: Of the 10 cases, 4 cases were male and 6 cases were female. The median age was 54 years (43-80 years). Two cases occurred in lymph nodes, 6 cases involved extranodal organs, and both lymph nodes and extranodal organs were involved in the other 2 cases. There were 4 cases (40%) with clinical stage Ⅲ/Ⅳ disease and 6 cases (60%) with clinical stage Ⅰ/Ⅱ disease. 40% (4/10) patients had international prognostic index (IPI) score ≥3. 50% (4/8) patients had bone marrow invasion. Two (20%) cases had B symptoms. 40% (4/10) patients had a history of hepatitis B virus infection. Five cases had the morphology of DLBCL, not otherwise specified (DLBCL-NOS); Two cases showed morphological features intermediate both DLBCL and Burkitt lymphoma; One case had a blastoid cytomorphology, and the other 2 cases failed to be classified accurately because of serious crushing artifacts of the tissue. Immunophenotypically, 80% of the cases were of germinal center B-cell (GCB) type and 20% were of non-GCB type. MYC/BCL2 double expression accounted for 78% (7/9), BCL6 positivity was found in 80% of the total cases, and the Ki-67 proliferation index was ≥80% in all cases. FISH showed that all 10 cases had MYC, BCL2 and BCL6 gene translocation rearrangement. EBV infection was consistently absent. All except one case received systemic treatment. The overall survival was 2.0-55.5 months (median, 16.8 months), and 1-year overall survival rate was 68.6%. The 1-year overall survival rates of patients with stage Ⅰ/Ⅱ disease and stage Ⅲ/Ⅳ disease were 100% and 25% respectively. Conclusion: THL mainly affects middle-aged and elderly patients, which occured more frequently in extranodal organs, and it is characterized by GCB immunophenotype and MYC/BCL2 double expression. A considerable number of patients have a clinical stage of Ⅰ/Ⅱ disease and a better prognosis in the current series, indicating that early identification of THL is of great importance for timely intervention and improving the prognosis.

In order to study the damage form and mechanism of coal mine roof, the stress distribution state in the stacked beam model was analyzed by using the stacked beam model and introducing the stress potential function; the model was simplified by using horizontal and vertical joints all over, and the damage range of coal seam roof was analyzed by combining Mohr-Coulomb strength criterion. The results show that the main factors of coal seam roof damage are layer separation caused by horizontal joints and fractures caused by vertical joints; the separation failure zone has a “hyperbolic-like” distribution with steep top and flat bottom, and the fracture damage zone has an “arch-shaped” distribution; with the increase of inter-bed friction coefficient with the increase of the interlayer friction coefficient, the height and width of the layer separation damage zone of the top plate decrease significantly, while the increase of the elastic modulus has less effect on the damage range of the top plate; meanwhile, with the increase of the indirect roof, the fracture height of the top plate gradually decreases and the layer separation width gradually increases.

Abstract Background In the study, we aimed to evaluate the ability of micro‐histology combined with cytology to improve the quality of slides and diagnose endometrial lesions. Methods Endometrial specimens were collected from Li Brushes. Every specimen was prepared for micro‐histological and cytological slides, using cell block (CB) and liquid‐based cytology (LBC) technologies. Semi‐quantitative scoring system was used to evaluate the qualities of slides. CB slides were assessed by 5‐category scoring system. Diagnostic accuracy was calculated in LBC, CB, and LBC + CB groups based on the histological gold standard. Endometrial atypical hyperplasia, and endometrial cancer were considered positive, whereas others were considered negative. Results A total of 167 patients were enrolled. CB slides were inferior to LBC slides only in cellularity (p

Gear vibration and noise are important parameters that affect the transmission performance. The vibration and noise control of the gear transmission system has become a very important field. Presently, the main methods of vibration control of the gear transmission system are increasing coincidence, shape modification, displacement, damping, etc. In this study, a novel method of staggered tooth phase of gears is proposed, the meshing principle of staggered phase tuning gears is studied, the calculation formula of time-varying meshing stiffness of staggered phase tuning gears is derived, and the mapping relationship between staggered phase and vibration response is studied. The experimental scheme of the parallel shaft spur gear pair with different staggering phases is designed, the experimental study of vibration reduction effect of gear pair with different staggering phases is carried out, and the experimental results are compared and analyzed with the simulation results.

To quantify the travel time and cost characteristics of mixed traffic involving electric vehicles (EVs) and fuel-powered vehicles on roads, in this paper, we comprehensively consider three factors affecting road impedance: queue length, waiting time, and service rate. Initially, a time characteristic function and a cost characteristic function for mixed traffic impedance are constructed. From the perspective of travel time, we consider the impact of EV penetration on the actual road capacity and introduce a capacity coefficient to modify the BPR (Bureau of Public Roads) road impedance function. Given that different types of vehicles might need to wait at charging stations, we employ queuing theory to calculate the queuing time at these stations and construct an impedance model that considers travel time. From the perspective of travel costs, we account for the energy consumption costs and road usage fees for different types of vehicles. The energy consumption cost for travel mileage is obtained by multiplying the unit mileage energy consumption cost of mixed traffic by the travel mileage. For road usage fees, we adopt the conventional method of multiplying the per-kilometer rate for each vehicle type by the travel mileage, thus constructing an impedance model that incorporates travel costs. Finally, in the numerical analysis section, based on the vehicle travel mileage, we categorize travel into short-, medium-, and long-distance trips for analysis. With the constructed mixed traffic impedance model, we conduct a detailed analysis of the travel time and cost characteristics of mixed traffic over different travel distances. We explore the specific impacts of the electric vehicle penetration rate, traffic flow volume, and travel mileage on road impedance. The results indicate that as the penetration rate of electric vehicles increases, the total energy consumption of the transportation system significantly decreases. Moreover, at high electric vehicle penetration rates, although an increase in traffic flow leads to higher traffic impedance and longer travel times, the overall travel costs are reduced. This demonstrates that increasing the penetration rate of electric vehicles positively contributes to reducing the energy consumption and costs of transportation systems.

Biochar is a soil amendment that has the potential to effectively improve soil salinization. However, there is a paucity of studies on sodium adsorption using biochar, and the adsorption mechanism remains unclear. To better understand the adsorption mechanism of Na+ on the surface of biochar, both pyrochar and hydrochar were produced at different temperatures. The capacity and influencing factors of Na+ adsorption in biochar were analyzed via batch adsorption experiments. Pore filling dominated the Na+ adsorption in the concentration of the NaCl solution when it was ≤100 mg/L, where wheat straw pyrochar (WB, 3.95–4.94 mg/g Na) and poplar wood chip pyrochar (PB, 0.62–0.70 mg/g Na) presented the release and adsorption of Na+, respectively. When the concentration of the NaCl solution was >100 mg/L, the adsorption capacity of WB (25.44–36.45 mg/g) was significantly higher than PB (4.46–6.23 mg/g). Both the adsorption and release of Na+ in hydrochar was insufficient. In a high concentration of NaCl solution, ion exchange became the key mechanism determining the adsorption of Na+ in pyrochar, in which K+ contributed to more than 94% of the Na+ adsorption. The findings proposed strategies for the structural design of biochar used for Na adsorption. These will promote the utilization of solid biowaste for sodium adsorption and the potential of soil salinization amendment for agriculture in arid lands.

IntroductionPharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort.MethodsBuffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models’ performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites.ResultsOverall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model.DiscussionThe development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

Introduction and Objectives: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. Materials and Methods: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. Results: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished β-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. Conclusions: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/β-catenin axis activation.

ABSTRACT: Objectives: Bedaquiline (BDQ) is a potent drug for treating drug-resistant tuberculosis (TB). Here, we analysed the resistance profiles of BDQ in CFZ-resistant clinical isolates and investigated the clinical risk factors of BDQ and CFZ cross/co-resistance. Methods: The AlarmarBlue microplate assay was performed to determine the minimum inhibitory concentration (MIC) of the CFZ-resistant Mycobacterium tuberculosis (MTB) clinical isolates to CFZ and BDQ. The clinical characteristics of the respective patients were analysed to explore the possible risk factors of BDQ resistance. The drug-resistance-associated genes including Rv0678, Rv1979c, atpE, pepQ and Rv1453 were sequenced and analysed. Results: A total of 72 clinical CFZ-resistant MTB isolates were collected; among these, half were identified as BDQ-resistant. The MIC value of BDQ closely correlated with CFZ (Spearman's q = 0.766, P < 0.005). Among the isolates with a MIC of CFZ ≥4 mg/L, 92.31% (12/13) were resistant to BDQ. Pre-XDR and exposure to BDQ or CFZ are the major risk factors for concurrent BDQ resistance. Among the 36 cross/co-resistant isolates, 50% (18/36) had mutations in Rv0678, 8.3% (3/36) had mutations in Rv0678+Rv1453, 5.6% (2/36) had mutations in Rv0678+Rv1979c, 2.8% (1/36) had mutations in Rv0678+Rv1979c+Rv1453, 2.8% (1/36) had mutations in atpE+Rv0678+Rv1453, 2.8% (1/36) had mutations in Rv1979c, and 27.7% (10/36) had no variations in the target genes. Conclusion: Nearly half of the CFZ-resistant isolates were still sensitive to BDQ, whereas this rate dramatically decreased among patients with pre-XDR TB or those who had been exposed to BDQ or CFZ.

Abstract Background The anesthetic states are accompanied by functional alterations. However, the dose-related adaptive alterations in the higher-order network under anesthesia, e. g. default mode network (DMN), are poorly revealed. Methods We implanted electrodes in brain regions of the rat DMN to acquire local field potentials to investigate the perturbations produced by anesthesia. Relative power spectral density, static functional connectivity (FC), fuzzy entropy of dynamic FC, and topological features were computed from the data. Results The results showed that adaptive reconstruction was induced by isoflurane, exhibiting reduced static and stable long-range FC, and altered topological features. These reconstruction patterns were in a dose-related fashion. Conclusion These results might impart insights into the neural network mechanisms underlying anesthesia and suggest the potential of monitoring the depth of anesthesia based on the parameters of DMN.

Objective To analyze the feasibility of hospitalized treatment of inpatients' mental disorders in a general hospital by an innovative consultation-liaison psychiatric hospitalized treatment mode. Methods Retrospective study involved the patients in the department of physical diseases of Peking Union Medical College Hospital who received hospitalized treatment in the Department of Psychological Medicine from July 1, 2020 to June 30, 2021(study group). All patients who received consultation-liaison psychiatry (CLP) services by Department of Psychological Medicine from January 1 to December 31 in 2019 were taken as the control group. The control group conducted liaison consultation and invited consultation based on the CLP concept, whereas the study group integrated a three-level check-in and follow-up system based on the CLP concept to facilitate the diagnosis and treatment of inpatient mental disorders through consultation and follow-up. According to the consultation records, the diagnosis results and intervention methods were extracted, and the consultation rate and follow-up rate were calculated. Results A total of 1196 patients (1647 times of consultation) were included in the study group and 1269 patients (1558 times of consultation) in control group. The consultation departments involved all the physical disease departments of the hospital. Compared with the control group, in the study group the general consultation rate[1.21%(1196/98 496) vs. 1.10%(1269/114 917)], the general follow-up rate[23.08%(276/1196) vs. 17.65%(224/1269)] were improved to varying degrees. The diagnosis results of consultation-liaison hospitalized treatment involved almost all mental disorders, among which anxiety disorder (18.76%, 309/1647), depressive disorder (17.1%, 282/1647) and brain organic mental disorder (16.45%, 271/1647) accounted for a high proportion. As for the intervention mode of patients, 30.66% (505/1647) only needed psychological counseling or treatment, and almost all patients had non-drug treatment intervention. Conclusion It is feasible for general hospitals to realize hospitalized treatment of mental disorders based on CLP concept, combined with three-level ward round and follow-up system, which can improve the accessibility of mental medical services.

There is a high prevalence of psychiatric comorbidity in general hospital inpatients of various physical departments. Psychiatric comorbidity may result in the difficulty in clinical communication, longer hospitalization, worse clinical outcomes and higher costs. However, psychiatric comorbidities are often neglected and left untreated. We believe this phenomenon is caused by complex problems including, but not limited to, insufficient recognition, insufficient invitation for consultation, clinical challenge of complex multiple-comorbidi-ties, and insufficient treatment. To address these problems, we developed consultation-liaison psychiatry system of resident-attending-professor rounds with fixed follow-ups to provide standardized care to general hospital inpatients with psychiatric comorbidity.

Hernia and life-threatening intestinal obstruction often result from abdominal wall injuries, and the regeneration of abdominal wall defects is limited due to the lack of biocompatible, antibacterial and angiogenic scaffolding materials for treating injured tissues. Taking inspiration from the facile preparation of dopamine polymerization and its surface modification technology, in this study, multi-therapeutic copper element was introduced into porcine small intestinal submucosa (SIS) bio-patches through polydopamine (PDA) deposition, in order to regenerate abdominal wall injury. In both in vitro antibacterial assays, cytocompatibility assays and in vivo abdominal wall repair experiments, the SIS/PDA/Cu bio-patches exhibited robust antibacterial efficiency (＞99%), excellent biocompatibility to cells (＞90%), and enhanced neovascularization and improved collagen maturity compared to other commercially available patches (3.0-fold higher than the PP mesh), due to their activation of VEGF pathway. These findings indicated the bio-patch was a promising application for preventing visceral adhesion, bacterial infection, and promoting soft tissue regeneration.

Background To clarify clinical importance of serum CA19-9, CA-125, and plasma D-dimer (D-D) levels in detecting spontaneously ruptured ovarian endometriosis (OE).Materials and Methods We retrospectively examined 173 patients with endometriosis out of 735 cases of OE between 2013 and 2019. Among these, 21 cases were diagnosed as “spontaneously ruptured” after surgery, while the remaining cases were unruptured. Venous blood was collected pre-operatively to detect CA19-9, CA-125, and D-D levels. A receiver operating characteristic curve analysis was applied to test clinical value of each marker.Results Among the 21 patients with ruptured OE, 16 had a history of pelvic cysts, 19 claimed sudden onsets of lower abdominal pain, and fluid accumulation were detected in cul-de-sac in only six participants by ultrasound. For serological investigation, both CA19-9 and D-D were significantly elevated in the ruptured OE group (343.09 ± 367.67 U/ml vs. 36.84 ± 40.01 U/ml, 3.39 ± 4.90 mg/L vs. 0.43 ± 0.29 mg/L, both p

Background/Objective Diabetes mellitus is a common “non-gout” disease with high incidence. Several studies have shown that serum uric acid level in patients with diabetes is higher than that in healthy individuals, and is accompanied by severe albuminuria and high serum creatinine (Scr). Recent clinical studies have found that uric acid-lowering therapy (such as allopurinol) could reduce urinary albumin excretion rates (UAER) and Scr, increase eGFR, and thus reduce kidney damage in patients with diabetes. Therefore, this meta-analysis [PROSPERO CRD42021274465] intended to evaluate the efficacy and safety of allopurinol in patients with diabetes mellitus.Methods We thoroughly searched five electronic resource databases for randomized controlled trials (RCTs) that compared the efficacy and safety of allopurinol versus conventional treatment or placebo for the treatment of patients with diabetes mellitus. Predetermined outcomes were considered continuous variables, mean difference (MD) was used for the determination of effect size (standardized mean difference [SMD] was used to determine the effect size when there were different evaluation criteria in different articles), and the corresponding 95% confidence interval (CI) was calculated. All outcome measures were analyzed using a random-effects model for data analysis.Results Ten eligible trials with a total of 866 participants were included in the meta-analysis. Allopurinol was more effective in decreasing serum uric acid (SUA) levels compared with conventional treatment (p = 0.0001) or placebo (p

Minimizing toxicity of herpes simplex virus 1 (HSV) based tools for anterograde tracing is important for functional studies. Here the authors generate an anterograde monosynaptic tracer system based on HSV amplicon, which shows fast tracing, bright labeling, low toxicity, input-defined postsynaptic neurons’ anterograde monosynaptic tracing feature, and has potential for functional mapping.

Abstract Neutrophil extracellular traps (NETs) has been demonstrated to regulate the metastasis of breast cancer. In this study, we showed that de novo cholesterol biosynthesis induced by ASPP2 depletion in mouse breast cancer cell 4T1 and human breast cancer cell MDA-MB-231 promoted NETs formation in vitro, as well as in lung metastases in mice intravenously injected with ASPP2-deficient 4T1 cells. Simvastatin and berberine (BBR), cholesterol synthesis inhibitors, efficiently blocked ASPP2-depletion induced NETs formation. Cholesterol biosynthesis greatly enhanced Coiled-coil domain containing protein 25 (CCDC25) expression on cancer cells as well as in lung metastases. CCDC25 expression was co-localized with caveolin-1, a lipid raft molecule, and was damped by inhibitor of lipid rafts formation. Our data suggest that cholesterol biosynthesis promotes CCDC25 expression in a lipid raft-dependent manner. Clinically, the expression of CCDC25 was positively correlated with the expression of 3-hydroxy-3-methylglutaryl-CoAreductase (HMRCG), and citrullinated histone H3 (H3cit), in tissues from breast cancer patients. High expression of CCDC25 and HMGCR was related with worse prognosis in breast cancer patients. In conclusion, our study explores a novel mechanism for de novo cholesterol biosynthesis in the regulation of CCDC25 expression, NETs formation and breast cancer metastasis. Targeting cholesterol biosynthesis may be promising therapeutic strategies to treat breast cancer metastasis.