Identification of steroid-induced osteonecrosis of the femoral head biomarkers based on immunization and animal experiments.

BACKGROUND: Steroid-induced osteonecrosis of femoral head (SONFH) is a severe health risk, and this study aims to identify immune-related biomarkers and pathways associated with the disease through bioinformatics analysis and animal experiments. METHOD: Using SONFH-related datasets obtained from the GEO database, we performed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to extract SONFH-related genes. A protein-protein interaction (PPI) network was then constructed, and core sub-network genes were identified. Immune cell infiltration and clustering analysis of SONFH samples were performed to assess differences in immune cell populations. WGCNA analysis was used to identify module genes associated with immune cells, and hub genes were identified using machine learning. Internal and external validation along with animal experiments were conducted to confirm the differential expression of hub genes and infiltration of immune cells in SONFH. RESULTS: Differential expression analysis revealed 502 DEGs. WGCNA analysis identified a blue module closely related to SONFH, containing 1928 module genes. Intersection analysis between DEGs and blue module genes resulted in 453 intersecting genes. The PPI network and MCODE module identified 15 key targets enriched in various signaling pathways. Analysis of immune cell infiltration showed statistically significant differences in CD8 + t cells, monocytes, macrophages M2 and neutrophils between SONFH and control samples. Unsupervised clustering classified SONFH samples into two clusters (C1 and C2), which also exhibited significant differences in immune cell infiltration. The hub genes (ICAM1, NR3C1, and IKBKB) were further identified using WGCNA and machine learning analysis. Based on these hub genes, a clinical prediction model was constructed and validated internally and externally. Animal experiments confirmed the upregulation of hub genes in SONFH, with an associated increase in immune cell infiltration. CONCLUSION: This study identified ICAM1, NR3C1, and IKBKB as potential immune-related biomarkers involved in immune cell infiltration of CD8 + t cells, monocytes, macrophages M2, neutrophils and other immune cells in the pathogenesis of SONFH. These biomarkers act through modulation of the chemokine signaling pathway, Toll-like receptor signaling pathway, and other pathways. These findings provide valuable insights into the disease mechanism of SONFH and may aid in future drug development efforts.

Recent advances in CAR-T therapy for the treatment of acute myeloid leukemia.

Chimeric antigen receptor T-cell (CAR-T) therapy, which has demonstrated notable efficacy against B-cell malignancies and is approved by the US Food and Drug Administration for clinical use in this context, represents a significant milestone in cancer immunotherapy. However, the efficacy of CAR-T therapy for the treatment of acute myeloid leukemia (AML) is poor. The challenges associated with the application of CAR-T therapy for the clinical treatment of AML include, but are not limited to, nonspecific distribution of AML therapeutic targets, difficulties in the production of CAR-T cells, AML blast cell heterogeneity, the immunosuppressive microenvironment in AML, and treatment-related adverse events. In this review, we summarize the recent findings regarding various therapeutic targets for AML (CD33, CD123, CLL1, CD7, etc.) and the results of the latest clinical studies on these targets. Thereafter, we also discuss the challenges related to CAR-T therapy for AML and some promising strategies for overcoming these challenges, including novel approaches such as gene editing and advances in CAR design.

Recent advances in CAR-T therapy for acute myeloid leukemia Acute myeloid leukemia (AML) remains a clinical challenge despite the advent of chimeric receptor T-cell (CAR-T) therapy, as there are obstacles hindering the application of CAR-T cells in AML. In this review, we discuss the results of current relevant clinical trials, existing treatment strategies for AML and recent advances in preclinical research to provide insight for overcoming the inefficacy of CAR-T therapy for AML.

Health economics study of paliperidone palmitate in the treatment of schizophrenia: a 12-month cohort study.

BACKGROUND: To analyze the economic benefits of paliperidone palmitate in the treatment of schizophrenia. METHODS: We collected 546 patients who met the diagnostic criteria for schizophrenia according to the 《International Statistical Classification of Diseases and Related Health Problems,10th》(ICD-10). We gathered general population data such as gender, age, marital status, and education level, then initiated treatment with paliperidone palmitate. Then Follow-up evaluations were conducted at 1, 3, 6, 9, and 12 months after the start of treatment to assess clinical efficacy, adverse reactions, and injection doses. We also collected information on the economic burden before and after 12 months of treatment, as well as the number of outpatient visits and hospitalizations in the past year to analyze economic benefits. RESULTS: The baseline patients totaled 546, with 239 still receiving treatment with paliperidone palmitate 12 months later. After 12 months of treatment, the number of outpatient visits per year increased compared to before (4 (2,10) vs. 12 (4,12), Z=-5.949, P < 0.001), while the number of hospitalizations decreased (1 (1,3) vs. 1 (1,2), Z = 5.625, P < 0.001). The inpatient costs in the direct medical expenses of patients after 12 months of treatment decreased compared to before (5000(2000,12000) vs. 3000 (1000,8050), P < 0.05), while there was no significant change in outpatient expenses and direct non-medical expenses (transportation, accommodation, meal, and family accompanying expenses, etc.) (P > 0.05); the indirect costs of patients after 12 months of treatment (lost productivity costs for patients and families, economic costs due to destructive behavior, costs of seeking non-medical assistance) decreased compared to before (300(150,600) vs. 150(100,200), P < 0.05). CONCLUSION: Palmatine palmitate reduces the number of hospitalizations for patients, as well as their direct and indirect economic burdens, and has good economic benefits.

Developing integrated person-centered care quality indicators for home health agencies in Shanghai, China: A modified Delphi-analytic hierarchy process study.

OBJECTIVES: To develop person-centered integrated care quality indicators for home health agencies in Shanghai, China. DESIGN: The study combined the Delphi method and the analytic hierarchy process (AHP). MATERIAL AND METHODS: The Delphi consultation questionnaire was distributed to experts in home healthcare in Shanghai, China. A panel of experts with experience in home healthcare in Shanghai, China, was selected. Purposive sampling was used to choose experts. In this study, ten experts were selected from within sub-fields of home healthcare, including nursing, health policy, quality improvement, person-centered care (PCC), and integrated care. RESULTS: The authority coefficient (Cr) in this study was 0.835. The coordination degree of experts' opinions, which is expressed by Kendall coordination coefficient W (a higher value, better coordination of the item), ranged from 0.352 to 0.386 (p < 0.001). The consistency ratio (CR) values for each level were less than 0.1. The quality indicator system included three first-level indicators, 15 second-level indicators, and 56 third-level indicators. CONCLUSIONS: A person-centered integrated care quality indicator system was developed for home health agencies. The findings from this study enable nurses, managers, and policymakers in home and community-based settings to evaluate person-centered integrated care quality using a robust framework. In addition, these indicators can also be used as a standardized tool to guide the development of long-term care services and supports (LTSS) for home-bound elderly.

Effect of tea polyphenols on intestinal barrier and immune function in weaned lambs.

Introduction: The purpose of this study was to explore the effects of tea polyphenols on growth performance, cytokine content, intestinal antioxidant status and intestinal barrier function of lambs, in order to provide reference for intestinal health of ruminants. Methods: Thirty weaned lambs (average initial weight 9.32 ± 1.72 kg) were randomly divided into five groups with six lambs in each group. The control group did not add anything but the basic diet mainly composed of Pennisetum and Corn, and the other four groups added 2, 4, 6 g/kg tea polyphenols and 50 mg/kg chlortetracycline to the basic diet, respectively. The experiment lasted for 42 days. Results: Dietary tea polyphenols improved the growth and stress response and reduced intestinal permeability of lambs (p > 0.05), while CTC did not affect the final lamb weight (p > 0.05). Both tea phenols and CTC significantly reduced inflammatory factors and enhanced the immune system (p > 0.05). Dietary tea polyphenols increased villus height, villus height/crypt depth, secretory immunoglobulin A (p > 0.05), and antioxidant enzymes, while decreasing MDA and apoptosis in the intestine (p > 0.05). However, compared with other groups, the content of T-AOC in jejunum did not change significantly (p > 0.05). Tea polyphenols also increased claudin-1 levels in the duodenum, jejunum, and ileum more than CTC (p > 0.05). CTC had a limited effect on the mRNA expression of Occludin and ZO-1, while tea polyphenols increased these in both the duodenum and ileum (p > 0.05). Conclusion: This study demonstrated that tea polyphenols can effectively improve the intestinal barrier of weaned lambs, and that they have anti-inflammatory and antioxidant effects similar to those of antibiotics. Thus, tea polyphenols could be used to replace antibiotics in ensuring safety of livestock products and in achieving the sustainable development of modern animal husbandry.

NRT1.2 overexpression enhances the synergistic interplay between ABA-generating bacteria and biochars in reducing heavy metal accumulation in pak choi.

The agricultural sector faces severe challenges owing to heavy metal (HM) contamination of farmlands, requiring urgent preventive measures. To address this, we investigated the impact of the synergistic application of Azospirillum brasilense, a growth-promoting rhizobacterium producing abscisic acid (ABA), and biochar to minimize HM accumulation in pak choi, using three distinct expression levels of the ABA transporter NRT1.2 in pak choi and three different types of contaminated soils as experimental materials. The results revealed that pak choi with low, medium, and high NRT1.2 expression intensity, when subjected to bacterial strain-biochar treatment, exhibited an increasing trend in ABA content compared to the control. Correspondingly, the aboveground HM content decreased by 1-49 %, 22-52 %, and 15-96 %, whereas the fresh weight increased by 12-38 %, 88-126 %, and 152-340 %, respectively, showing a significant correlation with NRT1.2 expression. Pearson correlation analysis demonstrated that NRT1.2 expression intensity was inversely associated with the combined treatment's reduction in HM accumulation and positively correlated with the promotional effect. Simultaneously, soil discrepancies significantly affected the combined treatment, which was likely associated with variations in the active forms of HM in each soil. Consequently, when employing ABA-producing bacteria for mitigating crop HM accumulation, selecting plants with higher relative NRT1.2 expression intensity, combined with biochar, is recommended.

Predicting coronary heart disease in Chinese diabetics using machine learning.

Diabetes, a common chronic disease worldwide, can induce vascular complications, such as coronary heart disease (CHD), which is also one of the main causes of human death. It is of great significance to study the factors of diabetic patients complicated with CHD for understanding the occurrence of diabetes/CHD comorbidity. In this study, by analyzing the risk of CHD in more than 300,000 diabetes patients in southwest China, an artificial intelligence (AI) model was proposed to predict the risk of diabetes/CHD comorbidity. Firstly, we statistically analyzed the distribution of four types of features (basic demographic information, laboratory indicators, medical examination, and questionnaire) in comorbidities, and evaluated the predictive performance of three traditional machine learning methods (eXtreme Gradient Boosting, Random Forest, and Logistic regression). In addition, we have identified nine important features, including age, WHtR, BMI, stroke, smoking, chronic lung disease, drinking and MSP. Finally, the model produced an area under the receiver operating characteristic curve (AUC) of 0.701 on the test samples. These findings can provide personalized guidance for early CHD warning for diabetic populations.

The application of microwaves in axillary hyperhidrosis: Curative effect observation of a pathological examination over 1 year.

BACKGROUND: In Asia, axillary hyperhidrosis is a frequent problem for many people, and the consequent excessive sweating can seriously affect many aspects of daily life and even lead to mental disorders. Microwave therapy is a new, non-invasive treatment method for axillary hyperhidrosis, whose energy and long-term effectiveness still needs to be clinically validated. OBJECTIVE: The aim of this study was to evaluate the clinical efficacy, safety, histological changes, and psychological status of microwave devices in the treatment of axillary hyperhidrosis and osmidrosis. METHOD: We conducted a prospective self-controlled study in a top-tier Chinese hospital. After a 5/5 energy treatment session, a skin biopsy was taken to observe histological changes both before and after treatment. An iodine starch test was used to determine the sweating range. We evaluated symptoms of improved efficacy using the Hyperhidrosis Disease Severity Scale (HDSS) and assessed changes in life status with the DLQI. In the case of concurrent underarm odor, odor-5, VAS, and Young-Jin Park grading were used to assess odor relief. The effect of odor on psychology was assessed by using a psychological status symptom checklist (scl-90). The study period was 1 year. RESULTS: We observed 20 patients in this study. Of those, 90% met the primary treatment endpoint of a decrease in axillary hyperhidrosis symptomatology to below grade 2 on the HDSS score (p < 0.001). Furthermore, 75% of patients achieved a treatment endpoint of at least 50% reduction in VAS (p < 0.001). 70% of patients achieved a treatment endpoint of at least 50% reduction in odor-5 (p < 0.001). The iodine starch test showed that the region decreased 99% from the baseline to 12 months after follow-up had ended (p < 0.001). Eight patients volunteered to undergo histological examination; their average light density of immunohistochemistry decreased from 1.04 (0.4-2.11) to 0.07 (0.04-0.46; p < 0.05). The immunohistochemical positive number for sweat glands was initially 104 (59.75-132.5) but was 41.5 (29.75-62) after the procedure. None of the patients experienced any serious adverse reactions. CONCLUSION: The treatment demonstrated high effectiveness, safety, and short-lived adverse reactions.

Potential drug targets for myocardial infarction identified through Mendelian randomization analysis and Genetic colocalization.

Myocardial infarction (MI) is a major cause of death and disability worldwide, but current treatments are limited by their invasiveness, side effects, and lack of efficacy. Novel drug targets for MI prevention are urgently needed. In this study, we used Mendelian randomization to identify potential therapeutic targets for MI using plasma protein quantitative trait loci as exposure variables and MI as the outcome variable. We further validated our findings using reverse causation analysis, Bayesian co-localization analysis, and external datasets. We also constructed a protein-protein interaction network to explore the relationships between the identified proteins and known MI targets. Our analysis revealed 2 proteins, LPA and APOA5, as potential drug targets for MI, with causal effects on MI risk confirmed by multiple lines of evidence. LPA and APOA5 are involved in lipid metabolism and interact with target proteins of current MI medications. We also found 4 other proteins, IL1RN, FN1, NT5C, and SEMA3C, that may have potential as drug targets but require further confirmation. Our study demonstrates the utility of Mendelian randomization and protein quantitative trait loci in discovering novel drug targets for complex diseases such as MI. It provides insights into the underlying mechanisms of MI pathology and treatment.

A promising product: Abscisic acid-producing bacterial agents for restricting cadmium enrichment in field vegetable crops.

Soil heavy metal contamination and its enrichment in the edible parts of crops have gained global concern. In this study, a compound bacterial agent possessing the ability to produce the plant hormone, abscisic acid (ABA), was applied to contaminated farmland in Hunan province. Its application reduced the concentration of Cd in radish, cabbage, mustard, and lettuce by 15-144%. Accordingly, the Cd contents in these vegetables were found to be below the maximum limits set by GB 2762-2017. Meanwhile, bacteria agents also led to a significant increase in crops yield by 45-82%. Furthermore, the nutritional indices, including soluble sugar and soluble protein increased by 18-66%, as well as the antioxidant indices, including total phenolic, ascorbate content, and DPPH capacity, enhanced by 12-76%, 10-49% and 50-140%, respectively. In conclusion, the use of ABA-producing bacteria is anticipated to be a novel approach for the safe use of soil with moderate and low pollution.

Plant growth-promoting rhizobacteria: A good companion for heavy metal phytoremediation.

Phytoremediation is an environment-friendly approach regarded as a potential candidate for remediating heavy metal (HM)-contaminated soils. However, the low efficacy of phytoremediation is a major limitation that hampers its large-scale application. Therefore, developing strategies to enhance phytoremediation efficacy for contaminated soils is crucial. Plant growth-promoting rhizobacteria (PGPR) considerably contribute to phytoremediation intensification. To improve the efficiency of plant-microbe symbiosis for remediation, the mechanisms underlying PGPR-stimulated HM accumulation and tolerance in plants should be comprehensively understood. This review focuses on hyperaccumulators, PGPR, and the mechanisms by which PGPR enhance phytoremediation from four aspects: providing nutrients to plants, secreting plant hormones and specific enzymes, inducing systemic resistance, and altering the bioavailability of HMs in soils. It also provides a theoretical and technical basis for future research on PGPR synergism in promoting the phytoextraction efficiency in HM-contaminated soils.

The influence of a color themed HMI on trust and take-over performance in automated vehicles.

Introduction: SAE Level 3 is known as conditional driving automation. As long as certain conditions are met, there is no need to supervise the technology and the driver can engage in non-driving related tasks (NDRTs). However, a human driver must be present and alert to take over when the automation is facing its system limits. When such an emergency takes place, the automation uses the human machine interface (HMI) to send a take-over request (TOR) to the driver. Methods: We investigated the influence of a color themed HMI on the trust and take-over performance in automated vehicles. Using a driving simulator, we tested 45 participants divided in three groups with a baseline auditory HMI and two advanced color themed HMIs consisting of a display and ambient lighting with the colors red and blue. Trust in automation was assessed using questionnaires while take-over performance was assessed through response time and success rate. Results: Compared to the baseline HMI, the color themed HMI is more trustworthy, and participants understood their driving tasks better. Results show that the color themed HMI is perceived as more pleasant compared to the baseline HMI and leads to shorter reaction times. Red ambient lighting is seen as more urging than blue, but HMI color did not significantly affect the general HMI perception and TOR performance. Discussion: Further research can explore the use of color and other modalities to express varying urgency levels and validate findings in complex on road driving conditions.

A gender specific risk assessment of coronary heart disease based on physical examination data.

Large-scale screening for the risk of coronary heart disease (CHD) is crucial for its prevention and management. Physical examination data has the advantages of wide coverage, large capacity, and easy collection. Therefore, here we report a gender-specific cascading system for risk assessment of CHD based on physical examination data. The dataset consists of 39,538 CHD patients and 640,465 healthy individuals from the Luzhou Health Commission in Sichuan, China. Fifty physical examination characteristics were considered, and after feature screening, ten risk factors were identified. To facilitate large-scale CHD risk screening, a CHD risk model was developed using a fully connected network (FCN). For males, the model achieves AUCs of 0.8671 and 0.8659, respectively on the independent test set and the external validation set. For females, the AUCs of the model are 0.8991 and 0.9006, respectively on the independent test set and the external validation set. Furthermore, to enhance the convenience and flexibility of the model in clinical and real-life scenarios, we established a CHD risk scorecard base on logistic regression (LR). The results show that, for both males and females, the AUCs of the scorecard on the independent test set and the external verification set are only slightly lower (<0.05) than those of the corresponding prediction model, indicating that the scorecard construction does not result in a significant loss of information. To promote CHD personal lifestyle management, an online CHD risk assessment system has been established, which can be freely accessed at http://lin-group.cn/server/CHD/index.html .

Effect of Cold-Water Irrigation on the Coblation Site for Post-Tonsillectomy Pain: A Prospective Randomized Clinical Study.

OBJECTIVE: To explore the effect of cold-water irrigation on post-tonsillectomy pain after coblation. METHODS: Data from 61 adult patients who underwent coblation tonsillectomy in our hospital from January 2019 to December 2020 were collected, and the patients were randomly divided into the cold-water irrigation group (Group 1) and the room-temperature irrigation group (Group 2). Group 1 was irrigated with ice water mixed saline with the help of a pressure band, and Group 2 was irrigated with room-temperature saline. During the operation, we monitored the temperature of the operating cavity in real time. We recorded the postoperative pain for 11 consecutive days from the day and the 10th day after the operation. RESULTS: The postoperative pain score was significantly lower than that in Group 2, except on the 2nd, 3rd and 7th and 8th days after the operation. CONCLUSION: The perfusion of cold water during coblation tonsillectomy is helpful to reduce postoperative pain.

Does green finance improve the industrial eco-efficiency in China?

Improving industrial eco-efficiency is of great significance for building a beautiful China and achieving its carbon peak and neutrality targets. Based on the panel data of 30 provinces in China from 2007 to 2018, this paper uses the super-efficiency SBM model to measure industrial eco-efficiency and empirically tests the influence of green finance on Chinese industrial eco-efficiency from the national and regional levels. The results show that the average level of industrial eco-efficiency in China is relatively stable during the study period with a large space for advancement. Second, there is spatial heterogeneity in Chinese industrial eco-efficiency, showing a gradually decreasing "southeast-northwest" ladder-like distribution. Third, the national-level regression results show that there is a significant "U-shaped" relationship between green financing and industrial eco-efficiency. In addition, the regression results at the regional level indicate that there is regional heterogeneity in the impact of green finance on industrial eco-efficiency. Finally, based on the research conclusions, specific suggestions on how green finance can improve industrial eco-efficiency in China are put forward, including vigorously developing green finance at the macro and micro levels, and exerting the positive effects of green finance in improving industrial eco-efficiency according to the area and the development level of green finance.

Gold-Catalyzed [4 + 1] Heterocyclization of Hydroxamic Acid and Nonactivated Alkyne: A Protocol to Construct 5-Methyl-1,4,2-dioxazole.

A novel gold-catalyzed [4 + 1] heterocyclization of nonactivated alkyne and hydroxamic acid is developed for the regiospecific synthesis of 5-methyl-1,4,2-dioxazole, which is an important structural motif in various bioactive molecules. The current methodology is characterized by high efficiency, simple operation, mild reaction conditions, and good functional group compatibility. Moreover, gram-scale synthesis and synthetic application toward bioactive molecular skeletons have been realized.

Fucosyltransferase 2: A Genetic Risk Factor for Intestinal Diseases.

The fucosyltransferase 2 gene (FUT2) mediates the synthesis of histoblood group antigens (HBGA) that occur in vivo from multiple organs, particularly on the surface of intestinal epithelial cells and body fluids. To date, many studies have demonstrated that the interaction of HBGA with the host microbiota is the cause of pathogenesis of intestinal diseases, making FUT2 non-secretor a risk factor for inflammatory bowel disease (IBD) due to the lack of HBGA. As HBGA also acts as an attachment site for norovirus (NoV) and rotavirus (RV), the non-secretor becomes a protective factor for both viral infections. In addition, the interaction of norovirus and rotavirus with symbiotic bacteria has been found to play an important role in regulating enteroviral infection in IBD. Given the current incomplete understanding of the complex phenomenon and the underlying pathogenesis of intestinal diseases such as IBD, it has recently been hypothesized that the FUT2 gene regulates intestinal bacteria through attachment sites, may help to unravel the role of FUT2 and intestinal flora in the mechanism of intestinal diseases in the future, and provide new ideas for the prevention and treatment of intestinal diseases through more in-depth studies.

Identifying patterns of clinical conditions among high-cost older adult health care users using claims data: a latent class approach.

OBJECTIVES: To identify patterns of clinical conditions among high-cost older adults health care users and explore the associations between characteristics of high-cost older adults and patterns of clinical conditions. METHODS: We analyzed data from the Shanghai Basic Social Medical Insurance Database, China. A total of 2927 older adults aged 60 years and over were included as the analysis sample. We used latent class analysis to identify patterns of clinical conditions among high-cost older adults health care users. Multinomial logistic regression models were also used to determine the associations between demographic characteristics, insurance types, and patterns of clinical conditions. RESULTS: Five clinically distinctive subgroups of high-cost older adults emerged. Classes included "cerebrovascular diseases" (10.6% of high-cost older adults), "malignant tumor" (9.1%), "arthrosis" (8.8%), "ischemic heart disease" (7.4%), and "other sporadic diseases" (64.1%). Age, sex, and type of medical insurance were predictors of high-cost older adult subgroups. CONCLUSIONS: Profiling patterns of clinical conditions among high-cost older adults is potentially useful as a first step to inform the development of tailored management and intervention strategies.