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Lung cancer has surpassed other types of cancer to become the primary cause of cancer-related deaths. Surgery stands as the foremost clinical treatment strategy available for tackling this condition, but it receives a low efficiency for most patients. In recent years, some adjuvant therapies are employed to improve the lung cancer treatment efficiency, such as chemotherapy, targeted therapy and immunotherapy. However, these strategies have not significantly increased overall survival of patients. Additionally, the random distribution of drugs will induce severe side effects. Nanomedicines have got great attentions to boost drug effect and reduce adverse reactions, including liposome-based nanoparticles, polymeric nanoparticles, inorganic nanoparticles, and exosomes. Importantly, nanomedicines contribute to improving drug bioavailability, stability and residency in target regions. Benefiting from the physiological characteristics of lung, the inhaled pulmonary delivery strategy in combination with nanomedicine will provide a non-invasive and effective strategy for treating lung cancer. Furthermore, the use of targeting ligands enables precise delivery of loaded drugs to lung cancer cells. Inhaled nanomedicine exhibits unique distribution and sustained release behaviors in the alveoli, amplifying the therapeutic effect and reducing side effects. This review aims to discuss various inhaled methods of delivering nanomedicine to treat lung cancer and also summarizes the clearance mechanism of nanomedicine in the lung. Overall, this review focuses on the application of different inhalable nanomedicines, which may inspire the development of more effective treatments against lung cancer.

High entropy alloys （HEAs） have excellent properties because they can form simple solid solution (SS) phases, including body-centered cubic (BCC) phase, face-centered cubic (FCC) phase, or FCC + BCC phase, so phase prediction is the first step in alloy design. In current research, machine learning (ML) approach had been widely used to guide the discovery and design of materials. The prediction of HEAs phase structure based on machine learning (ML) is a hot topic. In this work, five ML algorithms were utilized to predict HEAs for SS and amorphous (AM) phases based on 399 collected data sets, including 120 BCC alloys, 87 FCC alloys, 82 BCC + FCC alloys and 110 a.m. alloys. To enhance the model's accuracy, grid search and K-fold cross validation were used to optimize performance. Valence electron concentration (VEC) and ΔHmix exhibit high importance in prediction in compared to other parameters. The results show that the random forest can effectively distinguish BCC phase, FCC phase, mixed solid solution phase (FCC + BCC) and AM, with an accuracy is 0.87. After that, the CoCrFeNiAlx (x = 0, 0.5, 1) system alloys were characterized by XRD and SEM-EDS. The experimental results validated that the phase structure of CoCrFeNiAlx alloys changed from FCC to BCC + FCC and BCC with the increase of Al content, which is consistent with the ML prediction.

To verify the predictive accuracy of existing strength criteria on true triaxial strength experimental data, understand the characteristics of different strength criteria, and provide a basis for selecting strength criteria for engineering applications, ten commonly used rock strength criteria were selected and divided into MC and HB types. The distribution characteristics of the yield surfaces and yield curves of different criteria were compared and analyzed in the principal stress space and the π plane. Afterwards, based on the least absolutely deviation method, these ten strength criteria were used to predict 32 sets of true triaxial rock strength experimental data. The results showed that the range of undetermined parameters for MC type strength criteria was small and easy to determine, while the range of undetermined parameter for HB type criteria was large and difficult to determine the search range, in addition, the fitting process may not converge. The fitting accuracy of strength criteria for true triaxial experimental data depends on the sensitivity of rock strength to the intermediate principal stress. PH and GP criteria are the most sensitive to changes of the intermediate principal stress, followed by MWC and ML criteria, MGC and ZZ criteria, MCJP and HBWW criteria. PH and GP criteria overestimate the effect of the intermediate principal stress, resulting in the largest prediction errors, while the other three-dimensional strength criteria have high prediction accuracy and no significant differences. The research results can provide scientific basis for engineering design, geological hazard prediction, and mineral resource development.

Evidence has demonstrated that exoskeleton robots can improve intestinal function in patients with spinal cord injury (SCI). However, the underlying mechanisms remain unelucidated. This study investigated the effects of exoskeleton-assisted walking (EAW) on intestinal function and intestinal flora structure in T2-L1 motor complete paraplegia patients. The results showed that five participants in the EAW group and three in the conventional group reported improvements in at least one bowel management index, including an increased frequency of bowel evacuations, less time spent on bowel management per day, and less external assistance (manual digital stimulation, medication, and enema usage). After 8 weeks of training, the amount of glycerol used in the EAW group decreased significantly (p

IntroductionSimultaneous chemical phosphorus removal process using iron salts (Fe(III)) has been widely utilized in wastewater treatment to meet increasingly stringent discharge standards. However, the inhibitory effect of Fe(III) on the biological phosphorus removal system remains a topic of debate, with its precise mechanism yet to be fully understood.MethodsBatch and long-term exposure experiments were conducted in six sequencing batch reactors (SBRs) operating for 155 days. Synthetic wastewater containing various Fe/P ratios (i.e., Fe/P = 1, 1.2, 1.5, 1.8, and 2) was slowly poured into the SBRs during the experimental period to assess the effects of acute and chronic Fe(III) exposure on polyphosphate-accumulating organism (PAO) growth and phosphorus metabolism.ResultsExperimental results revealed that prolonged Fe(III) exposure induced a transition in the dominant phosphorus removal mechanism within activated sludge, resulting in a diminished availability of phosphorus for bio-metabolism. In Fe(III)-treated groups, intracellular phosphorus storage ranged from 3.11 to 7.67 mg/g VSS, representing only 26.01 to 64.13% of the control. Although the abundance of widely reported PAOs (Candidatus Accumulibacter) was 30.15% in the experimental group, phosphorus release and uptake were strongly inhibited by high dosage of Fe(III). Furthermore, the abundance of functional genes associated with key enzymes in the glycogen metabolism pathway increased while those related to the polyphosphate metabolism pathway decreased under chronic Fe(III) stress.DiscussionThese findings collectively suggest that the energy generated from polyhydroxyalkanoates oxidation in PAOs primarily facilitated glycogen metabolism rather than promoting phosphorus uptake. Consequently, the dominant metabolic pathway of communities shifted from polyphosphate-accumulating metabolism to glycogen-accumulating metabolism as the major contributor to the decreased biological phosphorus removal performance.

Ageing is an inevitable process that affects various tissues and organs of the human body, leading to a series of physiological and pathological changes. Mechanisms such as telomere depletion, stem cell depletion, macrophage dysfunction, and cellular senescence gradually manifest in the body, significantly increasing the incidence of diseases in elderly individuals. These mechanisms interact with each other, profoundly impacting the quality of life of older adults. As the ageing population continues to grow, the burden on the public health system is expected to intensify. Globally, the prevalence of musculoskeletal system diseases in elderly individuals is increasing, resulting in reduced limb mobility and prolonged suffering. This review aims to elucidate the mechanisms of ageing and their interplay while exploring their impact on diseases such as osteoarthritis, osteoporosis, and sarcopenia. By delving into the mechanisms of ageing, further research can be conducted to prevent and mitigate its effects, with the ultimate goal of alleviating the suffering of elderly patients in the future.

Objective To investigate the differences in myopia prevalence and ocular biometry in children and adolescents in Chongqing and Tibet, China.Design Cross-sectional study.Setting The study included children and adolescents aged 6–18 years in Chongqing, a low-altitude region, and in Qamdo, a high-altitude region of Tibet.Participants A total of 448 participants in Qamdo, Tibet, and 748 participants in Chongqing were enrolled in this study.Methods All participants underwent uncorrected visual acuity assessment, non-cycloplegic refraction, axial length (AL) measurement, intraocular pressure (IOP) measurement and corneal tomography. And the participants were grouped according to age (6–8, 9–11, 12–14 and 15–18 years group), and altitude of location (primary school students: group A (average altitude: 325 m), group B (average altitude: 2300 m), group C (average altitude: 3250 and 3170 m) and group D (average altitude: 3870 m)).Results There was no statistical difference in mean age (12.09±3.15 vs 12.2±3.10, p=0.549) and sex distribution (males, 50.4% vs 47.6%, p=0.339) between the two groups. The Tibet group presented greater spherical equivalent (SE, −0.63 (−2.00, 0.13) vs −0.88 (−2.88, –0.13), p

Physical therapists play a crucial role in guiding patients through effective and safe rehabilitation processes according to medical guidelines. However, due to the therapist-patient imbalance, it is neither economical nor feasible for therapists to provide guidance to every patient during recovery sessions. Automated assessment of physical rehabilitation can help with this problem, but accurately quantifying patients’ training movements and providing meaningful feedback poses a challenge. In this paper, an Expert-knowledge-based Graph Convolutional approach is proposed to automate the assessment of the quality of physical rehabilitation exercises. This approach utilizes experts’ knowledge to improve the spatial feature extraction ability of the Graph Convolutional module and a Gated pooling module for feature aggregation. Additionally, a Transformer module is employed to capture long-range temporal dependencies in the movements. The attention scores and weight matrix obtained through this approach can serve as interpretability tools to help therapists understand the assessment model and assist patients in improving their exercises. The effectiveness of the proposed method is verified on the KIMORE dataset, achieving state-of-the-art performance compared to existing models. Experimental results also illustrate the interpretability of the method in both spatial and temporal dimensions.

Abstract Objective Antimicrobial resistance (AMR) has emerged as a serious global public health crisis. In response, 2016, 14 ministries in China, under the leadership of the National Health Commission, collaboratively issued the National Action Plan (NAP) to Contain Antibacterial Resistance (2016–2020). The NAP outlines strategies for medical institutions to adopt stewardship and implement AMR control. The purpose of this study was to comprehend stakeholders’ perceptions of the NAP and explore the factors that influence its implementation in medical institutions. Methods Semi-structured interviews were conducted with practitioners from medical institution in March and April 2021. Interviews were audio-recorded, transcribed and analyzed using thematic analysis via the framework approach. Results Twenty practitioners, representing diverse roles (4 administrators, 7 clinicians, 3 microbiologists, 3 pharmacists, 3 nosocomial infection management personnel) from seven institutions, participated in the study. Substantial efforts have been undertaken to regulate the rational use of antibiotics and enhance the management of hospital infections. Participants demonstrated awareness and concern regarding antimicrobial resistance, with widespread support expressed for the NAP. Among all professions, there were varying opinions on whether they felt restricted in their daily work. The tertiary hospitals have established multidisciplinary cooperation mechanisms. Six main themes were identified as both barriers and facilitators to the implementation of the NAP in the medical institutions: individual factors, leadership, multidisciplinary collaboration, patient factors, training and culture. The capacity for administrative attention is constrained or limited, poor enforcement of guidelines, insufficient specialist staff and the liability pressure on clinicians were perceived barriers. To containing AMR in medical institutions, management of hospital infections, the public’s knowledge of antibiotics’ usage, routine education and multidisciplinary support would be facilitators. Conclusions Practitioners from medical institutions were highly supportive for the NAP. Consideration of practitioners’ perceived barriers and facilitators might enhance implementation of the NAP to contain antimicrobial resistance.

Abstract Background Although some studies suggest that robot-assisted technology can significantly improve upper limb function in stroke patients compared to traditional rehabilitation training, it is still necessary to incorporate an auxiliary intervention to alleviate negative emotions, thereby alleviating the post-stroke fatigue and encouraging patients to actively respond to rehabilitation. However, the effect of the auxiliary intervention is unknown. Objective To evaluate the effect of reminiscent music therapy combined with robot-assisted rehabilitation in elderly patients with upper limb dysfunction. Methods From November 2022 to March 2023, elderly patients with upper limb dysfunction after stroke were assigned to one of three groups, with group A receiving usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, group B receiving usual rehabilitation treatment and care plus robot-assisted rehabilitation, and group C receiving only usual rehabilitation treatment and care. Thirty patients completed this study, with 10 participants in each group. Activities of daily living, self-esteem, rehabilitation self-efficacy, positive emotion and upper limb function were measured before and after the intervention. One-way analysis of variance, paired-sample t-test, Kruskal-Wallis H test, Wilcoxon signed rank sum test and Chi-square test were used to analyze the data. Results According to the intragroup comparisons, in the three groups, all outcome measurements were significantly higher than those at baseline (all P

Abstract Background Breast cancer is the second leading cause of cancer-related death in women, and drug resistance during treatment is a major challenge. However, the mechanisms underlying drug resistance are not fully understood. Here we applied whole-exome sequencing (WES) to clarify resistant rules to Herceptin and tyrosine kinase inhibitors (TKIs). Methods There are 12 HER2+ breast cancer patients who were done WES. Samples from tumor and surrounding tissues underwent DNA sequencing and analysis. Various experimental and bioinformatics techniques were employed, including genomic capture, mutation analysis (Genome Analysis Toolkit (GATK), etc.), bioinformatics assessments, and drug-gene interaction investigations. Ultimately, the study explored the association of APOB gene expression with breast cancer recurrence rates, immune cell infiltration, and drug response. Results The C > T mutation frequency was highest in the Herceptin-insensitive (HI) and verification groups, codenamed YI, contrasting with the Herceptin-sensitive (HE) group. No microsatellite instability (MSI)-H patients were in the HE group, but both HI and YI groups had 1 each. Significant differences in transition-transversion (TiTv) were observed in the HI and YI groups rather than the HE group. In the TKI- insensitive (TI) group, C > T mutations were highest, differing from the TKI-sensitive (TE) group. TE group included 2 MSI-H patients. Significant differences in TiTv were found in the TI group rather than the TE group. Mutated APOB may resist Herceptin and TKI, increasing immune infiltration. We identified potential drugs targeting it. Conclusions Our study suggested that a higher percentage of C > T mutations, significant differences in TiTv, and MSI-H status may indicate Herceptin resistance, while a higher percentage of C > T mutations, significant differences in TiTv, and the absence of MSI-H may indicate TKI resistance in breast cancer patients. For patients resistant to both Herceptin and TKI, mutated APOB may play a crucial role in resistance.

Abstract Background It remains controversial whether the long-term use of statins or newer nonstatin drugs has a positive effect on human longevity. Therefore, this study aimed to investigate the genetic associations between different lipid-lowering therapeutic gene targets and human longevity. Methods Two-sample Mendelian randomization analyses were conducted. The exposures comprised genetic variants that proxy nine drug target genes mimicking lipid-lowering effects (LDLR, HMGCR, PCKS9, NPC1L1, APOB, CETP, LPL, APOC3, and ANGPTL3). Two large-scale genome-wide association study (GWAS) summary datasets of human lifespan, including up to 500,193 European individuals, were used as outcomes. The inverse-variance weighting method was applied as the main approach. Sensitivity tests were conducted to evaluate the robustness, heterogeneity, and pleiotropy of the results. Causal effects were further validated using expression quantitative trait locus (eQTL) data. Results Genetically proxied LDLR variants, which mimic the effects of lowering low-density lipoprotein cholesterol (LDL-C), were associated with extended lifespan. This association was replicated in the validation set and was further confirmed in the eQTL summary data of blood and liver tissues. Mediation analysis revealed that the genetic mimicry of LDLR enhancement extended lifespan by reducing the risk of major coronary heart disease, accounting for 22.8% of the mediation effect. The genetically proxied CETP and APOC3 inhibitions also showed causal effects on increased life expectancy in both outcome datasets. The lipid-lowering variants of HMGCR, PCKS9, LPL, and APOB were associated with longer lifespans but did not causally increase extreme longevity. No statistical evidence was detected to support an association between NPC1L1 and lifespan. Conclusion This study suggests that LDLR is a promising genetic target for human longevity. Lipid-related gene targets, such as PCSK9, CETP, and APOC3, might potentially regulate human lifespan, thus offering promising prospects for developing newer nonstatin therapies.

Abstract Introduction Inflammation and nerve injury promote astrocyte activation, which regulates the development and resolution of pain, in the spinal dorsal horn. APOE regulates lipid metabolism and is predominantly expressed in the astrocytes. However, the effect of astrocytic APOE and lipid metabolism on spinal cellular function is unclear. This study aimed to investigate the effect of spinal Apoe on spinal cellular functions using the complete Freund's adjuvant (CFA)-induced inflammatory pain mouse model. Methods After intraplantar injection of CFA, we assessed pain behaviors in C57BL6 and Apoe knockout (Apoe −/− ) mice using von Frey and Hargreaves’ tests and analyzed dorsal horn samples (L4-5) using western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and RNA sequencing. Results The Apoe levels were markedly upregulated at 2 h and on days 1 and 3 post-CFA treatment. Apoe was exclusively expressed in the astrocytes. Apoe −/− mice exhibited decreased pain on day 1, but not at 2 h, post-CFA treatment. Apoe −/− mice also showed decreased spinal neuron excitability and paw edema on day 1 post-CFA treatment. Global transcriptomic analysis of the dorsal horn on day 1 post-CFA treatment revealed that the differentially expressed mRNAs in Apoe −/− mice were associated with lipid metabolism and the immune system. Astrocyte activation was impaired in Apoe −/− mice on day 1 post-CFA treatment. The intrathecal injection of Apoe antisense oligonucleotide mitigated CFA-induced pain hypersensitivity. Conclusions Apoe deficiency altered lipid metabolism in astrocytes, exerting regulatory effects on immune response, astrocyte activation, and neuronal activity and consequently disrupting the maintenance of inflammatory pain after peripheral inflammation. Targeting APOE is a potential anti-nociception and anti-inflammatory strategy.

Early diagnosis of non-Hodgkin lymphoma (NHL) is crucial for effective management. We report an ultrasensitive electrochemical genosensor using multi-walled carbon nanotube (MWCNT)-graphene nanocomposite for detection of lymphoma biomarker gene. MWCNTs were dispersed over graphene nanoplatelets to form a conductive nanocomposite platform. The high surface area and π-π stacking ability enabled efficient immobilization of lymphoma probe DNA. Detailed materials characterization was performed using microscopy and spectroscopy techniques. The sensor was fabricated by drop-casting probe-conjugated nanocomposite suspension onto a glassy carbon electrode. The genosensor exhibited a wide dynamic range of 1 fM to 1 nM with a sensitivity of 0.895 kΩ per decade of target concentration. The sensor showed excellent selectivity for fully complementary target sequence over even single base mismatch. Hybridization detection by electrochemical impedance spectroscopy was further validated using differential pulse voltammetry which showed drastic reduction in redox peak current after incubating with target. The nanocomposite genosensor demonstrated good reproducibility with relative standard deviation of 3.72 % among five independently prepared electrodes. Clinical applicability was tested by spiking lymphoma gene biomarker in 10 % serum and recoveries of 93–99 % were obtained. The proposed MWCNT-graphene nanocomposite genosensor provides a simple, specific and ultrasensitive platform for point-of-care diagnosis of NHL.

Although significant differences in soil nitrogen levels exist under different paddy-upland rotations, the main reason for this is unclear. The nitrogen retention capacity and loss of ammonia volatilisation, leaching, etc. of paddy soil with large differences in nitrogen levels from two long-term rotations, garlic-rice and wheat-rice, were measured using the soil column simulation method. The results showed that the loss rate of leaching was only 5.4%, whereas that of ammonia volatilisation was up to 22.8%, which was the main nitrogen loss way of paddy soil under the two rotations. The average ammonia volatilisation rates under wheat-rice rotation with high and low nitrogen application rates were 12.1% and 40.2% higher than that under garlic-rice rotation, leading to a decrease in the total nitrogen loss amount and rate through ammonia volatilisation by 29.8% and 8.8%, respectively. As a result, nitrogen retention in the soil under garlic-rice rotation increased by 12.7%. In conclusion, the long-term garlic-rice rotation could significantly inhibit ammonia volatilisation, thus improving the soil nitrogen retention capacity. The straw return may increase soil organic matter content, reduce ammonia volatilisation loss, and enhance soil nitrogen retention capacity and productivity.

Membranous nephropathy (MN) is a glomerular disease mediated by autoimmune complex deposition, with approximately 30% of cases attributed to secondary causes. Among them, malignant tumors are a significant cause of secondary MN. Recent advancements in the identification of MN-specific antigens, such as THSD7A and NELL-1, suggest a potential association with malignant tumors, yet definitive proof of this relationship remains elusive. Therefore, this article aims to review the distribution of MN-specific antigens in patients with MN caused by malignant tumors and the possible role of these antigens in the pathogenesis of the disease.

BackgroundStroke is the main disease that causes the burden of neurological disease, leading to upper limb dysfunction and affecting their self-care abilities. Robot-assisted rehabilitation therapy has been gradually used in the rehabilitation of upper limb function after stroke. However, it would be beneficial to explore auxiliary interventions such as reminiscent music therapy, a combination of music and reminiscent, to relieve negative emotions and post-stroke fatigue and improve rehabilitation outcomes. This protocol aims to evaluate the effectiveness of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients.MethodsThis trial is a single-blind, three-arm randomized controlled trial. Older stroke patients with upper limb dysfunction will be recruited. Participants will be randomly assigned to receive usual rehabilitation treatment and care, usual rehabilitation treatment and care plus robot-assisted rehabilitation and reminiscent music therapy, or usual rehabilitation treatment and care plus robot-assisted rehabilitation. Robot-assisted rehabilitation will be conducted by rehabilitation doctors five times per week for 3 weeks. In experimental group 1, a reminiscent song list will be played for patients. The primary outcome is activities of daily living. All outcomes will be evaluated at baseline and in the week immediately post-intervention.DiscussionWe are conducting the first randomized controlled trial on the effects of reminiscent music therapy combined with robot-assisted rehabilitation in older stroke patients. It is expected that this study, if proven effective in improving the activities of daily living in older stroke patients with upper limb dysfunction, will provide evidence-based rehabilitation strategies for medical staff.Clinical Trial Registration: ChiCTR2200063738.

PurposeThe Diagnosis-Related Group (DRG) or Diagnosis-Intervention Packet (DIP) payment system, now introduced in China, intends to streamline healthcare billing practices. However, its implications for clinical pharmacists, pivotal stakeholders in the healthcare system, remain inadequately explored. This study sought to assess the perceptions, challenges, and roles of clinical pharmacists in China following the introduction of the DRG or DIP payment system.MethodsQualitative interviews were conducted among a sample of clinical pharmacists. Ten semi-structured interviews were conducted, either online or face to face. Thematic analysis was employed to identify key insights and concerns related to their professional landscape under the DRG or DIP system.ResultsClinical pharmacists exhibited variable awareness levels about the DRG or DIP system. Their roles have undergone shifts, creating a balance between traditional responsibilities and new obligations dictated by the DRG or DIP system. Professional development, particularly concerning health economics and DRG-based or DIP-based patient care, was highlighted as a key need. There were calls for policy support at both healthcare and national levels and a revised, holistic performance assessment system. The demand for more resources, be it in training platforms or personnel, was a recurrent theme.ConclusionThe DRG or DIP system’s introduction in China poses both opportunities and challenges for clinical pharmacists. Addressing awareness gaps, offering robust policy support, ensuring adequate resource allocation, and recognizing the evolving role of pharmacists are crucial for harmoniously integrating the DRG or DIP system into the Chinese healthcare paradigm.

Abstract Background Breast carcinoma (BRCA) is one of the most common, fatal, and aggressive cancers, with increasing morbidity that has a major impact on human health. PIK3CD appears to have important roles in the beginning and advancement of various forms of human cancer, according to mounting data. However,the particular role and mechanism of PIK3CD in BRCA remains not fully identified. Methodology The Cancer Genome Atlas (TCGA, https://portal.gdc.cancer.gov/ ), Genotype-Tissue Expression (GTEx) data and the UCSC Xena browser ( https://xenabrowser.net ) data were used in this study’s initial pan-cancer analysis of PIK3CD expression and prognosis. Circular RNAs (circRNAs) that regulated the expression of PIK3CD were subsequently found using a combination of in silico investigations of expression, correlation, and survival. Measurements of PIK3CD expression and an analysis of the in vitro function of PIK3CD in BRCA cells were performed using real-time RT-PCR, Western blotting and Transwell assays. Results In BRCA GLI2, RAB32, LAMB1, MGAT2, ITGA8, CHF, COL6A3 and PRRX1-miR-30b-5p axis was identified as the most likely upstream CircRNA-related route of PIK3CD. PIK3CD was correlated with the expression of EMT markers. The PIK3CD cDNA improved the capacity for invasion and migration. The expression of PIK3CD was linked to some of the m1A/m5C/m6A regulators. Additionally, it was discovered that the expression of PIK3CD was found to be highly connected to the expression of immunological checkpoints, immune cell biomarkers, and tumor immune cell invasion. Conclusions Our findings reveal that PIK3CD expression is associated with prognosis, EMT, and tumor immune infiltration in BRCA patients.

The COVID-19 pandemic has changed the world and has presented the scientific community with unprecedented challenges. Infection is associated with overproduction of proinflammatory cytokines secondary to hyperactivation of the innate immune response, inducing a cytokine storm and triggering multiorgan failure and significant morbidity/mortality. No specific treatment is yet available. For thousands of years, Panax notoginseng has been used to treat various infectious diseases. Experimental evidence of P. notoginseng utility in terms of alleviating the cytokine storm, especially the cascade, and improving post-COVID-19 symptoms, suggests that P. notoginseng may serve as a valuable adjunct treatment for COVID-19 infection.

IntroductionIn precision agriculture, accurately diagnosing apple frog-eye leaf spot disease is critical for effective disease management. Traditional methods, predominantly relying on labor-intensive and subjective visual evaluations, are often inefficient and unreliable.MethodsTo tackle these challenges in complex orchard environments, we develop a specialized deep learning architecture. This architecture consists of a two-stage multi-network model. The first stage features an enhanced Pyramid Scene Parsing Network (L-DPNet) with deformable convolutions for improved apple leaf segmentation. The second stage utilizes an improved U-Net (D-UNet), optimized with bilinear upsampling and batch normalization, for precise disease spot segmentation.ResultsOur model sets new benchmarks in performance, achieving a mean Intersection over Union (mIoU) of 91.27% for segmentation of both apple leaves and disease spots, and a mean Pixel Accuracy (mPA) of 94.32%. It also excels in classifying disease severity across five levels, achieving an overall precision of 94.81%.DiscussionThis approach represents a significant advancement in automated disease quantification, enhancing disease management in precision agriculture through data-driven decision-making.

BackgroundIdiopathic membranous nephropathy (IMN) is the most common pathological type in adults with nephrotic syndrome. Many target antigens have been discovered. However, dual antigen-positive IMN patients are very rare, with only a few such cases being briefly described in various studies. There is no specific study on the clinicopathological and prognostic characteristics of dual antigen-positive IMN patients, and the disease characteristics of such patients remain unclear.MethodsImmunohistochemical staining of PLA2R, THSD7A, and NELL-1 was conducted on kidney tissue samples obtained from patients diagnosed with IMN. Simultaneously, the presence of corresponding serum antibodies was determined. Patients exhibiting positivity for dual antigens were included in the study, identified either through tissue staining or serum antibody detection. We retrospectively collected their clinical, pathological, and follow-up data and measured their serum antibody levels at multiple time points. Additionally, the same type of dual antigen-positive IMN cases reported in the literature were reviewed to extract clinical, pathological, and prognostic information. We compared the data for all of the above dual antigen-positive and PLA2R single-positive IMN cases at our center.ResultsWe identified 6 IMN patients with dual antigen positivity at our center, approximately 0.7% of whole MN series; the previous literature reports 43 IMN patients with dual antigen positivity, the proportion ranged from 0.2% to 2.8%. The IgG1 positivity rate in the renal tissue of the dual antigen-positive patients at our center was significantly lower than that of dual antigen-positive patients previously reported (16.7% vs. 100.0%, p=0.015), but there was no significant difference in clinical or prognostic aspects. Patients with dual antigen positivity reported at our center and in the literature were combined and compared with PLA2R single-positive IMN reported at our center. Compared with PLA2R single-positive IMN patients, dual antigen-positive IMN patients had a higher renal tissue IgG1 positivity rate (58.3% vs. 22.3%, p=0.016), and the time required to achieve remission was longer [13.5 (3.3,35.0) vs. 3.0 (1.0,8.0), p=0.052]. Overall, The changes in urine protein were consistent with the changes in serum PLA2R antibody levels in dual antigen-positive IMN patients.ConclusionsFor patients with primary membranous nephropathy who did not attain remission following prolonged treatment, multiple target antigen staining should still be actively performed, even with positivity for the PLA2R target antigen.

BackgroundSome studies have investigated the association between vitamin D levels and precocious puberty (PP) but with limited sample sizes and inconsistent conclusions across studies.MethodsUntil July 2022, a comprehensive electronic search of works of literature was conducted in MEDLINE, Web of Science, and CNKI (Chinese National Knowledge Infrastructure). A systematic review and meta-analysis of 15 case-control studies with 2145 cases and 2063 controls was conducted to explore the relationship between vitamin D and PP. Stratified analyses by year of publication, country, diagnosis category of PP, child’s sex, and methods of 25(OH)D test were conducted.ResultsThere was a negative correlation between 25(OH)D concentrations and PP in all study populations (SMD = -1.046, 95%CI = -1.366, -0.726). The pooled SMD remained significant in Chinese studies (SMD = -1.113, 95%CI = -0.486, -0.741), studies published before or after 2018 (SMD = -0.9832 and -1.185, 95%CI = -2.044, -1.133 and -1.755, -0.726), studies with female children (SMD = -1.114, 95%CI = -1.446, -0.781), and studies using electrochemiluminescence to detect 25(OH)D (SMD = -0.999, 95%CI = -1.467, -0.531). Vitamin D deficiency also increased the risk of PP (OR = 1.531, 95%CI = 1.098, 2.134). Unfortunately, heterogeneity was high in all analyses, and there was some publication bias.ConclusionThis systematic review and meta-analysis demonstrated an association between vitamin D and precocious puberty. We recommend more high-quality studies, especially prospective cohort studies with big sample sizes or some randomized controlled intervention trials, to validate the reliability of the results.

Membranous nephropathy (MN) is a glomerular disease. Crocin is isolated from saffron and gardenia. Its antioxidant, anti-inflammatory, anti-hyperlipidemic, anti-atherosclerotic, anti-tumor, free-radical scavenging and neuroprotective activities have been well established. We investigated the biological functions of crocin and its related mechanisms in MN. We established an experimental passive Heymann nephritis (PHN) rat model induced by anti-Fx1A antiserum. The rats were divided into sham, sham + crocin, PHN, PHN + crocin, and PHN + enalapril groups. Blood samples and kidneys of rats were collected for estimation of biochemical parameters in serum and oxidative stress indicators in kidney tissues. Histopathological changes of renal tissues were evaluated by hematoxylin and eosin, periodic acid-Schiff (PAS) and Masson staining. The podocyte number was estimated by immunohistochemistry staining of Wilms tumor type 1 (WT1). The deposition of rat anti-rabbit IgG antibodies, complement C3 and C5b-9 was detected by immunofluorescence staining. Western blotting was performed to measure the levels of Sirtuin 1 (Sirt1), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase 1 (HO-1) and apoptosis-related proteins. The total cholesterol, triglycerides, creatinine, blood urea nitrogen, urine volume and urine albumin of PMN rats were significantly reduced by crocin. Additionally, crocin attenuated the renal histopathological changes. Moreover, the oxidative stress damage and podocyte loss and immune injury were relieved by crocin in PHN rats. Mechanistically, crocin administration activated the Sirt1/Nrf2/HO-1 pathways. The results provide a scientific basis that crocin could alleviate MN by inhibiting immune injury and podocyte damage through activating the Sirt1/Nrf2/HO-1 pathways.

AbstractBackground Chronic kidney disease-associated pruritus (CKD-aP) is very common and sometimes refractory to treatment in hemodialysis patients. In a trial conducted in Japan, nalfurafine, effectively reduced itching of treatment-resistant CKD-aP. Our present bridging study aimed to evaluate the efficacy and safety of nalfurafine in Chinese cohort with refractory CKD-aP.Methods In this phase III, multicenter bridging study conducted at 22 sites in China, 141 Chinese cases with refractory CKD-aP were randomly (2:2:1) assigned to receive 5 μg, 2.5 μg of nalfurafine or a placebo orally for 14 days in a double-blind manner. The primary end point was the mean decrease in the mean visual analogue scale (VAS) from baseline.Results A total of 141 patients were included. The primary endpoint analysis based on full analysis set (FAS), the difference of mean VAS decrease between 5 μg nalfurafine and placebo group was 11.37 mm (p = .041); the difference of mean VAS decrease between 2.5 μg and placebo group was 8.81 mm (p = .110). Both differences were greater than 4.13 mm, which met its predefined success criterion of at least 50% efficacy of the key Japanese clinical trial. The per protocol set (PPS) analysis got similar results. The incidence of adverse drug reactions (ADRs) was 49.1% in 5μg, 38.6% in 2.5 μg and 33.3% in placebo group. The most common ADR was insomnia, seen in 21 of the 114 nalfurafine patients.Conclusions Oral nalfurafine effectively reduced itching with few significant ADRs in Chinese hemodialysis patients with refractory pruritus.

Abstract Hearing impairment is a global health problem that affects social communications and the economy. The damage and loss of cochlear hair cells and spiral ganglion neurons (SGNs) as well as the degeneration of neurites of SGNs are the core causes of sensorineural hearing loss. Biotechnologies and biomedical engineering technologies provide new hope for the treatment of auditory diseases, which utilizes biological strategies or tissue engineering methods to achieve drug delivery and the regeneration of cells, tissues, and even organs. Here, the advancements in the applications of biotechnologies (including gene therapy and cochlear organoids) and biomedical engineering technologies (including drug delivery, electrode coating, electrical stimulation and bionic scaffolds) in the field of hearing reconstruction are presented. Moreover, we summarize the challenges and provide a perspective on this field.

Nowadays, the importance of logistics management has been increasingly realized in industry and society. However, current educational approaches in logistics management seem unable to effectively equip students with the necessary skills to cope with practical issues after graduation. Recently, contest-based education has attracted logistics management educators’ attention, but how it can be effectively utilized in this discipline is largely unclear. To fill this gap, this study followed a system approach and analyzed the factors influencing student performance in logistics management contests in China using interpretive structural modelling (ISM) and Matrice d’ Impacts Croisés-Multiplication Appliquée á un Classement (MICMAC). The results suggest that the driving forces for improving student performance in contests are the instructors’ encouragement and their previous experience in instructing contests. Also, the contestants’ previous experience in academic contests, team leadership, and effectiveness of communication between instructors and contestants are critical influencing factors. Based on the results, the educational strategies for effective utilization of contest-based education in logistics management are discussed. This study contributes to the existing literature by using a system modeling approach to clarify the mechanisms of contest-based education adoption in logistics management as well as informing university teachers and higher education institutes about strategies to improve their education quality.

This paper shows that desertification combating practices decline incomes of farmers and herders, and China needs to adapt its ecological programmes to address the impacts of climate change and create positive synergies to combat desertification.

BackgroundThe alkaline phosphatase-to-albumin ratio (APAR) has been demonstrated to be a promising non-invasive biomarker for predicting prognosis in certain diseases. However, the relationship between APAR and prognosis in non-dialysis chronic kidney disease (CKD) patients remains unclear. This study aims to identify the association between APAR and prognosis among CKD stages 1–4 in China.MethodsPatients with CKD stages 1–4 were consecutively recruited from 39 clinical centers in China from 2011 to 2016. New occurrences of end-stage kidney disease (ESKD), major adverse cardiovascular and cerebrovascular events, and all-cause deaths were the outcome events of this study. Subdistribution hazard competing risk and Cox proportional hazards regression models were adopted.ResultsA total of 2,180 participants with baseline APAR values were included in the analysis. In the primary adjusted analyses, higher APAR level [per 1-standard deviation (SD) increase in natural logarithm transformed (ln-transformed) APAR] was associated with 33.5% higher risk for all-cause deaths [adjusted hazard ratio (HR) 1.335, 95% confidence interval (CI) 1.068–1.670]. In addition, there was evidence for effect modification of the association between APAR and ESKD by baseline estimated glomerular filtration rate (eGFR) (P interaction < 0.001). A higher APAR level (per 1-SD increase in ln-transformed APAR) was associated with a greater risk of ESKD among participants with eGFR ≥ 60 ml/min/1.73 m2 (adjusted SHR 1.880, 95% CI 1.260–2.810) but not in eGFR < 60 ml/min/1.73 m2.ConclusionHigher APAR levels in patients with CKD stages 1–4 seemed to be associated with an increased risk of all-cause death. Thus, APAR appears to be used in risk assessment for all-cause death among patients with CKD stages 1–4.

Citric acid is the most important organic acid in melon and has a great influence on fruit flavor quality. ATP-citrate (pro-S) lyase (ACL) is a key regulator in the acetyl-CoA pathway and plays an important role in citric acid metabolism. In this study we analyzed the structure and phylogenetics of CmACL genes and their functions in sugar and acid accumulation in melon. A total of four CmACL genes were identified in the melon genome, and phylogenetic analysis assigned these genes into the α subfamily (CmACLα1 and CmACLα2) and the β subfamily (CmACLβ1 and CmACLβ2). Conserved motif and gene structure analyses showed that members of the same subfamily shared identical conserved motifs and gene structures, and probably have similar biological functions. Analysis of cis-acting elements revealed that CmACL promoter sequences contained regulatory elements related to light, stress, phytohormones, and growth and development, indicating that CmACL genes may be involved in melon growth and stress responses. The prediction of protein interaction network showed that CmACL proteins were closely related to the proteins belonging to tricarboxylic acid cycle, glyoxylic acid cycle and glycolytic pathway, suggesting that CmACL proteins may play an important role in sugar and acid metabolism. The expression of CmACLβ1 was significantly and positively correlated with sucrose content, and CmACLβ2 expression was significantly positively correlated with citric acid content, suggesting that CmACLβ1 and CmACLβ2 have important roles in sugar and acid accumulation in melon. Our results offer novel insights and avenues for the regulation of sugar and acid levels in melon and provide a theoretical foundation for breeding high-quality melon cultivars.

Objective: To determine whether exoskeleton-assisted walking (EAW) improves pulmonary ventilation function, motor function and related body structure, and activities equivalently as the conventional exercise program for people with spinal cord injury (SCI). Methods: Forty participants (7 females and 33 males; age 37.1±12.0 years) with thoracic SCI were randomized into two groups and undertook 16 sessions of 50–60 min training (4 days/week). Participants in the EAW group received EAW trainings, such as assisted standing, walking, and climbing the stairs. The control group received a conventional exercise program. Outcomes were measured at baseline and upon completion of treatment. Results: After trainings, the EAW group improved more than the control group in the forced vital capacity (FVC, 0.53 L [0.01–1.06 L]), predicted FVC% (19.59 [6.63–32.54]) and forced expiratory volume in 1s (0.61 L [0.15–1.07 L]), basic activities of daily living (BADL) (19.75 [10.88–28.62]), and distal femoral cartilage. Participants in the EAW group completed 6-minute walk test with median 17.3 meters while wearing the exoskeleton. There was no difference in trunk and lower extremity motor function, bone mineral density, and adverse events ( ${P}$ > 0.05). Conclusion: In people with lower thoracic neurological level of SCI, EAW training has potential benefits to facilitate pulmonary ventilation function, walking, BADL and thickness of cartilage comparing to a conventional excise program. Significance: This study provided more evidence for using EAW in clinic, and partly proved EAW had equivalent effects as conventional exercise program, which may combine with conventional exercise program for reducing burden of therapists in the future.

It is generally thought that complement activation in human membranous nephropathy (MN) occurs predominantly via the lectin or alternative pathway. Here, the authors show that the classical pathway is the dominant form of complement activation in MN and a pathogenic driver of the disease.

The main problem faced by traditional three-dimensional (3D) holographic displays is the time-consuming and poor flexibility of the hologram generation process. To address this issue, this paper proposes a non-iterative 3D computer-generated hologram (SFS-ORAP-PC-3D) method based on single full-support optimized random phase and phase compensation. Combining the full-support optimized random phase (FS-ORAP) method and the 3D layer-based idea to efficiently and non-iteratively generate the phase-only hologram of a 3D object with arbitrary positions and sizes using single FS-ORAP, thus overcoming the limitations of the original ORAP method in target position and size. Meanwhile, using a Fresnel lens for phase compensation allows for free selection of reconstruction planes. Numerical and optical experiments validate the feasibility of our proposed method.

Manganese (Mn) is an essential trace element, but insufficient or excessive bodily amounts can induce neurotoxicity. Mn can directly increase neuronal insulin and activate insulin-like growth factor (IGF) receptors. As an important cofactor, Mn regulates signaling pathways involved in various enzymes. The IGF signaling pathway plays a protective role in the neurotoxicity of Mn, reducing apoptosis in neurons and motor deficits by regulating its downstream protein kinase B (Akt), mitogen-activated protein kinase (MAPK), and mammalian target of rapamycin (mTOR). In recent years, some new mechanisms related to neuroinflammation have been shown to also play an important role in Mn-induced neurotoxicity. For example, DNA-sensing receptor cyclic GMP–AMP synthase (cCAS) and its downstream signal efficient interferon gene stimulator (STING), NOD-like receptor family pyrin domain containing 3(NLRP3)-pro-caspase1, cleaves to the active form capase1 (CASP1), nuclear factor κB (NF-κB), sirtuin (SIRT), and Janus kinase (JAK) and signal transducers and activators of the transcription (STAT) signaling pathway. Moreover, autophagy, as an important downstream protein degradation pathway, determines the fate of neurons and is regulated by these upstream signals. Interestingly, the role of autophagy in Mn-induced neurotoxicity is bidirectional. This review summarizes the molecular signaling pathways of Mn-induced neurotoxicity, providing insight for further understanding of the mechanisms of Mn.

Carotenoids are important pigments in pepper fruits. The colors of each pepper are mainly determined by the composition and content of carotenoid. The ‘ZY’ variety, which has yellow fruit, is a natural mutant derived from a branch mutant of ‘ZR’ with different colors. ZY and ZR exhibit obvious differences in fruit color, but no other obvious differences in other traits. To investigate the main reasons for the formation of different colored pepper fruits, transcriptome and metabolome analyses were performed in three developmental stages (S1–S3) in two cultivars. The results revealed that these structural genes (PSY1, CRTISO, CCD1, CYP97C1, VDE1, CCS, NCED1 and NCED2) related to carotenoid biosynthesis were expressed differentially in the two cultivars. Capsanthin and capsorubin mainly accumulated in ZR and were almost non-existent in ZY. S2 is the fruit color-changing stage; this may be a critical period for the development of different color formation of ZY and ZR. A combination of transcriptome and metabolome analyses indicated that CCS, NCED2, AAO4, VDE1 and CYP97C1 genes were key to the differences in the total carotenoid content. These new insights into pepper fruit coloration may help to improve fruit breeding strategies.

Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.

Abstract Spinal cord injury is a severe central nervous system injury, and developing appropriate drug delivery platforms for spinal nerve regeneration is highly anticipated. Here, we propose a basic fibroblast growth factor (bFGF)‐loaded methacrylate gelatin (GelMA) hydrogel microsphere with ideal performances for spinal cord injury repair. Benefitting from the precise droplet manipulation capability of the microfluidic technology, the GelMA microspheres possess uniform and satisfactory size and good stability. More importantly, by taking advantage of the porous structures and facile chemical modification of the GelMA microspheres, bFGF could be easily loaded and gradually released. By co‐culturing with neural stem cells, it is validated that the bFGF‐loaded GelMA microspheres could effectively promote the proliferation and differentiation of neural stem cells. We also confirm the effective role of the bFGF‐loaded GelMA microspheres in nerve repair of spinal cord injury in rats. Our results demonstrate the potential value of the microspheres for applications in repairing central nervous system injuries.

ObjectiveThe aim of this study is to compare the efficacy and safety of complete multi-level vs. iliac-only revascularization for the treatment of concomitant iliac and superficial femoral artery (SFA) occlusive disease.MethodsA total of 139 consecutive adult patients with severe stenosis and occlusive iliac and SFA disease with Rutherford categories 2–5 underwent multi-level (n = 71) and iliac-only (n = 68) revascularization at the Department of Intervention Vascular Surgery, Peking University Third Hospital, and Aerospace Center Hospital, between March 2015 and June 2017. Improvement in Rutherford class, perioperative major adverse events, the length of stay, survival rate, and limb salvage rate were assessed. The neutrophil–lymphocyte ratio and platelet–lymphocyte ratio were compared between the two groups.ResultsAt 48 months, improvement in the Rutherford category was observed in the two groups with no significant difference (P = 0.809). Additionally, the two groups were similar concerning the primary patency (84.0% vs. 79.1%, P = 0.717) and limb salvage rate (93.1% vs. 91.3%, P = 0.781). A higher proportion of the perioperative major adverse events (33.8% vs. 27.9%, P = 0.455), the all-cause mortality (11.3% vs. 8.8%, P = 0.632), and the average length of hospital stay [7.0 (6.0, 11.0) vs. 7.0 (5.0, 8.0), P = 0.037] were seen in the multi-level group compared with the iliac-only group.ConclusionFor concomitant iliac and superficial femoral artery occlusive disease, iliac-only revascularization has favorable efficacy and safety outcomes compared with complete multi-level revascularization in selected patients with patent profunda femoris artery and at least one healthy outflow tract of the infrapopliteal artery.

Abstract Background Maintenance of cancer stem‐like cell (CSC) stemness supported by aberrantly regulated cancer cell metabolism is critical for CSC self‐renewal and tumor progression. As a key glycolytic enzyme, hexokinase 2 (HK2) plays an instrumental role in aerobic glycolysis and tumor progression. However, whether HK2 directly contribute to CSC stemness maintenance in small cell lung cancer (SCLC) is largely unclear. In this study, we aimed to investgate whether HK2 independent of its glycolytic activity is directly involved in stemness maintenance of CSC in SCLC. Methods Immunoblotting analyses were conducted to determine the expression of HK2 in SCLC CSCs and their differentiated counterparts. CSC‐like properties and tumorigenesis of SCLC cells with or without HK2 depletion or overexpression were examined by sphere formation assay and xenograft mouse model. Immunoprecipitation and mass spectrometry analyses were performed to identify the binding proteins of CD133. The expression levels of CD133‐associated and CSC‐relevant proteins were evaluated by immunoblotting, immunoprecipitation, immunofluorescence, and immunohistochemistry assay. RNA expression levels of Nanog, POU5F1, Lin28, HK2, Prominin‐1 were analyzed through quantitative reverse transcription PCR. Polyubiquitination of CD133 was examined by in vitro or in vivo ubiquitination assay. CD133+ cells were sorted by flow cytometry using an anti‐CD133 antibody. Results We demonstrated that HK2 expression was much higher in CSCs of SCLC than in their differentiated counterparts. HK2 depletion inhibited CSC stemness and promoted CSC differentiation. Mechanistically, non‐mitochondrial HK2 directly interacted with CD133 and enhanced CD133 expression without affecting CD133 mRNA levels. The interaction of HK2 and CD133 promoted the binding of the deubiquitinase ubiquitin‐specific protease 11 (USP11) to CD133, thereby inhibiting CD133 polyubiquitylation and degradation. HK2‐mediated upregulation of CD133 expression enhanced the expression of cell renewal regulators, SCLC cell stemness, and tumor growth in mice. In addition, HK2 expression was positively correlated with CD133 expression in human SCLC specimens, and their expression levels were associated with poor prognosis of SCLC patients. Conclusions These results revealed a critical non‐metabolic function of HK2 in promotion of cancer cell stemness. Our findings provided new insights into the multifaceted roles of HK2 in tumor development.

Abstract Repair of spinal cord injury (SCI) depends on microenvironment improvement and the reconnection between injured axons and regenerated neurons. Here, we fabricate a GelMA-MXene hydrogel nerve conduit with electrical conductivity and internal-facing longitudinal grooves and explore its function in SCI repair. It is found that the resultant grooved GelMA-MXene hydrogel could effectively promote the neural stem cells (NSCs) adhesion, directed proliferation and differentiation in vitro. Additionally, when the GelMA-MXene conduit loaded with NSCs (GMN) is implanted into the injured spinal cord site, effective repair capability for the complete transection of SCI was demonstrated. The GMN group shows remarkable nerve recovery and significantly higher BBB scores in comparison to the other groups. Therefore, GMN with the microgroove structure and loaded with NSCs is a promising strategy in treating SCI.

Rheumatoid Arthritis (RA) remains a major global public health challenge. Disease-modifying anti-rheumatic drugs (DMARDs) are standard therapeutic drugs for RA. Conventional DMARDs (c-DMARDs) are a subgroup of approved synthetic DMARDs. The c-DMARDs experienced lesser response with longer disease duration or drug exposure, and unwanted adverse events (AEs). The combination treatments (CTs) of c-DMARDs and Chinese Herbal Medicines (CHMs) were often used in RA clinical trials for increasing the therapeutic effectiveness and reducing the AEs. This systematic review aimed to evaluate the efficacy and safety of the CTs for RA. Databases were searched from inception to October 2020 for identification of randomized controlled trials (RCTs) that investigated the CTs in the management of RA. Twenty-three RCTs with 2,441 participants were included. The assessments and analyses found CTs improved American College of Rheumatology (ACR) 20 (RR: 1.33, 95% CI [1.21, 1.45], 10 studies, n=1,075) and alleviated AEs (RR: -0.40, 95% CI [-0.30, -0.53], 19 studies, n=2,011) in comparison with c-DMARDs. The CTs also significantly improved RA symptoms and patient-reported outcomes; reduced disease activity score (DAS) 28, serum acute-phase reactants and RA biomarkers. The five most commonly used herbs in included studies were Angelicae Sinensis Radix, Paeoniae Radix Alba, Cinnamomi Ramulus, Glycyrrhizae Radix et Rhizoma, and Clematidis Radix et Rhizoma. Pharmacological studies indicated these CHMs could contribute to the outcomes. The integrated CHMs potentially increased the overall effectiveness of c-DMARDs and alleviated AEs in management of RA. Large sample and rigorously designed RCTs are required for future studies.

High-efficiency fertilizers suitable for mechanical spraying can improve the fertilizer application and utilization efficiency. In this study, two types of granular compound fertilizers suitable for unmanned air vehicle spraying were developed using urea, potassium chloride, humic acid, and an amino acid synergist according to the fertilization requirements of rice at the booting stage. The physical and chemical properties of the compound fertilizers were analyzed by Fourier transform infrared spectroscopy and scanning electron microscopy. The release kinetics of the fertilizer was studied via a soil column leaching experiment. The effect of fertilizer particles on unmanned air vehicle spraying uniformity was studied via an orthogonal simulation experiment. Results showed that the chemical interaction between compound-fertilizer raw materials formed complexes such as C-NH-C and -CO-NH-, which caused a change in fertilizer particle morphology. This led to chemical monolayer adsorption or internal fertilizer diffusion, which in turn delayed the fertilizer release by 5−10 d. A simulation bench test showed that the fertilizer particle hardness and roundness exceeded 20 N and 85%, respectively, while the particle size was in the range of 2.07−5.13 mm, which resulted in good unmanned air vehicle spraying uniformity with a lateral variation coefficient of less than 15%. Finally, the experimental field results demonstrated that the new compound fertilizers, when sprayed by an unmanned air vehicle, could improve the economic benefit by 916−2742 CNY ha−1 without reducing the nitrogen utilization rate and rice yield. The new compound fertilizers exhibit delayed release, good spraying uniformity, and improved economic benefit, rendering them suitable for large-scale promotion and application.

Objective: To explore the synergistic effect of tea polysaccharide-tea polyphenol on the improvement of oxidative stress damage in brain induced by D-galactose (D-Gal) in mice, and to provide a basic for the development of functional food. Methods: The oxidative stress model was induced by D-Gal, and 12 mice were retained as the normal control group. The mice that were successfully modeled were randomly divided into a model control group and a positive drug group (reduced glutathione, 200 mg/kg·bw), tea polyphenol group (50 mg/kg·bw), and low-dose, medium-dose and high-dose tea polysaccharide-tea polyphenol groups (40, 100, 250 mg/kg·bw). Gavage for 45 days to determine the content of biomacromolecule oxidative damage markers and enzyme antioxidant system related indicators in the brain of homogenate mice. Results: Compared with the model control group, the levels of the high-dose tea polysaccharide-tea polyphenol group of the biomacromolecule oxidative damage markers including protein carbonyl (PCO), advanced oxidation (AOPP), 3-nitrotyrosine (3-NT), malondialdehyde (MDA), 8-iso-prostaglandin(8-iso-PG), 8-hydroxy-2'-desoxyguanosine (8-OHdG), 5- hydroxy-2' -desoxyguanosine (5-OH-DG) were significantly decreased by 22.95%, 15.23%, 15.29%, 25.23%, 23.15%, 32.36%, 28.63%, respectively (P0.05). Compared with the tea polyphenol group, the levels of PCO，AOPP，3-NT，MDA，8-iso-PG，8-OHdG，5-OH-DG of the high-dose tea polysaccharide-tea polyphenol group were decreased by 4.06%, 1.81%, 4.96%, 10.12%, 3.40%, 12.50%(P>0.05), respectively and the level of 8-OHdG was significantly decreased by 21.19% (P0.05) and the level of GPX was significantly increased by 5.84% (P

Stress urinary incontinence (SUI) is a common gynecological urinary system disease, and globally, 200 million or more people suffer from it. However, the existing literature mostly focuses on postpartum urinary incontinence (UI) or UI in middle-aged and elderly people, with little focus on primiparas. To analyse urinary incontinence prevalence and its risk factors in primiparas and establish a nomogram prediction model, 360 parturients were recruited from three hospitals between April and September 2021. A homemade electronic questionnaire was used to investigate the general demographic and perinatal characteristics of primiparas. The SUI was diagnosed by the physicians. Logistic regression analysis of independent risk factors for SUI and a nomogram prediction model were established. Ninety people were diagnosed as SUI. The number of pregnancies (OR = 3.322, 95% CI = 1.473–7.492), residence (OR = 5.451, 95% CI = 2.725–10.903), occupation (OR = 3.393, 95% CI = 1.144–10.064), education level (OR = 3.551, 95% CI = 1.223–10.308), delivery method (OR = 10.270, 95% CI = 4.090–25.789), and oxytocin use (OR = 2.166, 95% CI = 1.142–4.109) were independent risk factors for SUI. The C-index of the nomogram prediction model was 0.798 (95% CI = 0.749–0.846). The POPDI score, CRADI score, UDI score, and PFDI scores of women with SUI were significantly higher than those of non-SUI women, while I-QOL scores were significantly lower than those of non-SUI women. In conclusion, the prevalence of SUI among primiparas in Fuyang, China, was 25.00%, which exhibited a large impact on the quality of life of puerperae. The present study successfully established an individualized nomogram prediction model of SUI for primiparas with good discrimination and diagnostic efficiency, which was helpful for the early clinical identification of high-risk primiparas with SUI.

Abstract Background Pediatric non-Wilms renal tumors (NWRTs), which comprise a small proportion of renal tumors, are a heterogeneous group of neoplasms with variable malignant potential, mortality, and response to treatment. We performed this study to determine the clinical characteristics, management and prognosis of children with Pediatric NWRTs. Methods Medical records of all patients (n = 139) treated for NWRTs over a 12-year period (2008.01–2019.10) at a single center were reviewed retrospectively. Results The histopathological groups of NWRTs included malignant rhabdoid tumor of the kidney (MRTK) (n: 30, 21.6%), renal cell cancer (RCC) (n: 26,18.7%), clear cell sarcoma of the kidney (CCSK) (n: 24,17.3%), congenital mesoblastic nephroma (CMN) (n: 21,15.1%), cystic nephroma (CN) (n: 16,11.5%), metanephric tumors (n: 12, 8.6%), renal angiomyoliporma (RAML) (n: 3, 2.2%), renal primitive neuroectodermal tumor (n: 2, 1.4%), renal hemangioma (n: 2, 1.4%), inflammatory myofibroblastic tumor (n: 2, 1.4%), ossifying renal tumor of infancy (ORTI) (n: 1, 0.7%). The distribution of all malignant NWRTs, including MRTK, CCSK, RCC and PNET, according to stage was as follows: stages I (n = 26), II (n = 16), III (n = 29), and IV (n = 11). The summary table shows the treatment offered to children with NWRTs. A total of 123 children were followed up for an average of 42 months. Sixteen children were lost to follow-up. Tumor-free survival was observed in 94 children. One patient who suffered from RCC is currently receiving targeted therapy and survives with the tumor. Twenty-eight children (22.8%) died. Conclusions Pediatric NWRTs comprise 19.1% of all renal tumors in our single center. Most NWRTs can readily be distinguished using a range of immunohistochemical markers. Molecular genetic profiling has allowed much progress in the understanding of this group of tumors, making diagnosis and classification less difficult. The mainstay treatment of malignant NWRTs, including MRTK, CCSK, RCC and PNET, is comprehensive treatment. The mainstay treatment of benign NWRTs, including RAML, CN, ORTI, CMN, metanephric tumors, and renal hemangioma, is surgical resection alone and when the tumor diameter is smaller than 7 cm and the tumor locates in one pole, NSS can be performed.

Nervous system injuries remain a great challenge due to limited natural tissue regeneration capabilities. Neural tissue engineering has been regarded as a promising approach for repairing nerve defects, which utilizes external biomaterial scaffolds to allow cells to migrate to the injury site and repair the tissue. Particularly, scaffolds with anisotropic structures biomimicking the native extracellular matrix (ECM) can effectively guide neural orientation and reconnection. Here, the advancements of scaffolds with anisotropic structures in the field of neural tissue engineering are presented. The fabrication strategies of scaffolds with anisotropic structures and their effects in vitro and in vivo are highlighted. We also discuss the challenges and provide a perspective of this field.

A genome-wide association study in a Chinese population identifies SNPs associated with serum copper levels. Mendelian randomization analysis reveals causal effects on multiple human phenotypes in East Asian and European populations.

IntroductionTriptolide (TPL) is a promising plant-derived compound for clinical therapy of multiple human diseases; however, its application was limited considering its toxicity.MethodsTo explore the underlying molecular mechanism of TPL nephrotoxicity, a network pharmacology based approach was utilized to predict candidate targets related with TPL toxicity, followed by deep RNA-seq analysis to characterize the features of three transcriptional elements include protein coding genes (PCGs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) as well as their associations with nephrotoxicity in rats with TPL treatment.Results & DiscussionAlthough the deeper mechanisms of TPL nephrotoxcity remain further exploration, our results suggested that c-Jun is a potential target of TPL and Per1 related circadian rhythm signaling is involved in TPL induced renal toxicity.

The worldwide sheep population comprises more than 1000 breeds. Together, these exhibit a considerable morphological diversity, which has not been extensively investigated at the molecular level. Here, we analyze whole-genome sequencing individuals of 1,098 domestic sheep from 154 breeds, and 69 wild sheep from seven Ovis species. On average, we detected 6.8%, 1.0% and 0.2% introgressed sequence in domestic sheep originating from Iranian mouflon, urial and argali, respectively, with rare introgressions from other wild species. Interestingly, several introgressed haplotypes contributed to the morphological differentiations across sheep breeds, such as a RXFP2 haplotype from Iranian mouflon conferring the spiral horn trait, a MSRB3 haplotype from argali strongly associated with ear morphology, and a VPS13B haplotype probably originating from urial and mouflon possibly associated with facial traits. Our results reveal that introgression events from wild Ovis species contributed to the high rate of morphological differentiation in sheep breeds, but also to individual variation within breeds. We propose that long divergent haplotypes are a ubiquitous source of phenotypic variation that allows adaptation to a variable environment, and that these remain intact in the receiving population probably due to reduced recombination.

IntroductionImmunoglobulin A nephropathy (IgAN) presents various clinical manifestations and pathological phenotypes. Approximately 5% of patients with IgAN present with early onset nephrotic syndrome, mild mesangial lesions, and diffuse foot process effacement of podocytes, which resemble minimal change disease (MCD). These patients are defined as MCD-IgAN. Whether MCD-IgAN is a special type of IgAN or simply MCD accompanied by IgA deposition remains controversial.MethodsA total of 51 patients diagnosed with MCD-IgAN at Beijing Anzhen Hospital from January 2010 to September 2022 were recruited. The clinical and pathological characteristics of IgA-MCD were analyzed. Patients with IgAN but without MCD (non-MCD-IgAN) and healthy participants were enrolled as controls. Galactose-deficient immunoglobulin A1 (Gd-IgA1) and complement C3 were detected both in the circulation and in renal tissues.ResultsWe found that the levels of serum Gd-IgA1 were lower in participants with MCD-IgAN than in those with non-MCD-IgAN, but higher than in healthy participants. Gd-IgA1 was rarely deposited in the glomeruli of participants with MCD-IgAN, with a positive rate of only 13.7% (7/51); in contrast, the positive rate in participants with non-MCD-IgAN was 82.4% (42/51). Among renal Gd-IgA1-positive patients, Gd-IgA1 and immunoglobulin A (IgA) colocalized along the glomerular mesangial and capillary areas. Interestingly, we found that the circulating levels of complement C3 were significantly higher in participants with MCD-IgAN than in participants with non-MCD-IgAN. In addition, the intensity of C3c in glomeruli in participants with MCD-IgAN was significantly weaker than in participants with non-MCD-IgAN.ConclusionsOur study suggests that, in MCD-IgAN, most of the IgA that is deposited on glomeruli is not the same pathogenic Gd-IgA1 as found in general IgAN. Complement activation both in the circulation and in the renal locality was much weaker in MCD-IgAN than in non-MCD-IgAN. Our study suggests that IgAN with MCD might be MCD with coincidental IgA deposition.