Astragaloside IV protects renal tubular epithelial cells against oxidative stress-induced injury by upregulating CPT1A-mediated HSD17B10 lysine succinylation in diabetic kidney disease.

Tubular injury and oxidative stress are involved in the pathogenesis of diabetic kidney disease (DKD). Astragaloside IV (ASIV) is a natural antioxidant. The effects and underlying molecular mechanisms of ASIV on DKD have not been elucidated. The db/db mice and high-glucose-stimulated HK2 cells were used to evaluate the beneficial effects of ASIV in vivo and in vitro. Succinylated proteomics was used to identify novel mechanisms of ASIV against DKD and experimentally further validated. ASIV alleviated renal dysfunction and proteinuria, downregulated fasting blood glucose, and upregulated insulin sensitivity in db/db mice. Meanwhile, ASIV alleviated tubular injury, oxidative stress, and mitochondrial dysfunction in vivo and in vitro. Mechanistically, ASIV reversed downregulated 17beta-hydroxysteroid dehydrogenase type 10 (HSD17B10) lysine succinylation by restoring carnitine palmitoyl-transferase1alpha (Cpt1a or CPT1A) activity in vivo and in vitro. Molecular docking and cell thermal shift assay revealed that ASIV may bind to CPT1A. Molecular dynamics simulations demonstrated K99 succinylation of HSD17B10 maintained mitochondrial RNA ribonuclease P (RNase P) stability. The K99R mutation of HSD17B10 induced oxidative stress and disrupted its binding to CPT1A or mitochondrial ribonuclease P protein 1 (MRPP1). Importantly, ASIV restored the interaction between HSD17B10 and MRPP1 in vivo and in vitro. We also demonstrated that ASIV reversed high-glucose-induced impaired RNase P activity in HK2 cells, which was suppressed upon K99R mutation of HSD17B10. These findings suggest that ASIV ameliorates oxidative stress-associated proximal tubular injury by upregulating CPT1A-mediated K99 succinylation of HSD17B10 to maintain RNase P activity.

Prevalence and Risk Factors of Stroke in Inpatients with Type 2 Diabetes Mellitus in China.

OBJECTIVE: The prevalence and the cluster characteristics of risk factors of stroke were assessed in a Chinese diabetic population. METHODS: Clinical data of 30 693 inpatients who were diagnosed with type 2 diabetes mellitus (T2DM) and admitted between 2013 and 2018 were retrospectively analyzed. The age-standardized prevalence of stroke was estimated using the 2010 Chinese population census data, and risk factors were analyzed by multiple imputation and regression. RESULTS: The crude and standardized prevalence rates of stroke in patients with T2DM were 34.4% and 21.5%, respectively, and 85.2% of the stroke patients had ischemic stroke. Nearly half of the patients who experienced stroke had clusters of more than 4 risk factors. Compared with no-risk-factor clustering, the risk of stroke significantly increased 3-4 times in the presence of more than 4 risk-factor clusters (P<0.001). Hypertension was the most common major risk factor for ischemic stroke [odds ratio (OR), 2.34; 95% confidence interval (CI), 2.18-2.50] and hemorrhagic stroke (OR, 3.68; 95% CI 2.95-4.59; P<0.001). Moreover, a 1-standard-deviation increase in fasting blood glucose (FBG) was significantly negatively correlated with ischemic stroke risk, and the same change in FBG was significantly associated with an 8% increased risk of hemorrhagic stroke. CONCLUSION: The prevalence of stroke in patients with T2DM is rather high, and the clustering of risk factors is associated with the development of stroke in T2DM patients. Risk factors differ in different stroke subtypes. Identifying risk factors for a specific high-risk group is necessary.

Combined use of Panax notoginseng and leech provides new insights into renal fibrosis: Restoration of mitochondrial kinetic imbalance.

In this study, we aimed to investigate the protective effects of Panax notoginseng and leech (PL) on renal fibrosis and explore the mechanisms underlying their actions. For this study, we created an adenine-induced renal fibrosis model in SD rats to investigate the protective effect of PL on renal fibrosis and explore its underlying mechanism. Initially, we assessed the renal function in RF rats and found that Scr, BUN, and urine protein content decreased after PL treatment, indicating the protective effect of PL on renal function. Histological analysis using HE and Masson staining revealed that PL reduced inflammatory cell infiltration and decreased collagen fiber deposition in renal tissue. Subsequently, we analyzed the levels of α-SMA, Col-IV, and FN, which are the main components of the extracellular matrix (ECM), using IHC, RT-qPCR, and WB. The results demonstrated that PL was effective in reducing the accumulation of ECM, with PL1-2 showing the highest effectiveness. To further understand the underlying mechanisms, we conducted UPLC-MS/MS analysis on the incoming components of the PL1-2 group. The results revealed several associations between the differential components and antioxidant and mitochondrial functions. This was further confirmed by enzyme-linked immunosorbent assay and biochemical indexes, which showed that PL1-2 ameliorated oxidative stress by reducing ROS and MDA production and increasing GSH and SOD levels. Additionally, transmission electron microscopy results indicated that PL1-2 promoted partial recovery of mitochondrial morphology and cristae. Finally, using RT-qPCR and WB, an increase in the expression of mitochondrial fusion proteins Mfn1, Mfn2, and Opa1 after PL1-2 treatment was observed, coupled with a decline in the expression and phosphorylation of mitochondrial cleavage proteins Fis and Drp1. These findings collectively demonstrate that PL1-2 ameliorates renal fibrosis by reducing oxidative stress and restoring mitochondrial balance.

Exploring the environmental risks and seasonal variations of potentially toxic elements (PTEs) in fine road dust in resource-based cities based on Monte Carlo simulation, geo-detector and random forest model.

The environmental pollution caused by mineral exploitation and energy consumption poses a serious threat to ecological security and human health, particularly in resource-based cities. To address this issue, a comprehensive investigation was conducted on potentially toxic elements (PTEs) in road dust from different seasons to assess the environmental risks and influencing factors faced by Datong City. Multivariate statistical analysis and absolute principal component score were employed for source identification and quantitative allocation. The geo-accumulation index and improved Nemerow index were utilized to evaluate the pollution levels of PTEs. Monte Carlo simulation was employed to assess the ecological-health risks associated with PTEs content and source orientation. Furthermore, geo-detector and random forest analysis were conducted to examine the key environmental variables and driving factors contributing to the spatiotemporal variation in PTEs content. In all PTEs, Cd, Hg, and Zn exhibited higher levels of content, with an average content/background value of 3.65 to 4.91, 2.53 to 3.34, and 2.15 to 2.89 times, respectively. Seasonal disparities were evident in PTEs contents, with average levels generally showing a pattern of spring (winter) > summer (autumn). PTEs in fine road dust (FRD) were primarily influenced by traffic, natural factors, coal-related industrial activities, and metallurgical activities, contributing 14.9-33.9 %, 41.4-47.5 %, 4.4-8.3 %, and 14.2-29.4 % to the total contents, respectively. The overall pollution and ecological risk of PTEs were categorized as moderate and high, respectively, with the winter season exhibiting the most severe conditions, primarily driven by Hg emissions from coal-related industries. Non-carcinogenic risk of PTEs for adults was within the safe limit, yet children still faced a probability of 4.1 %-16.4 % of unacceptable risks, particularly in summer. Carcinogenic risks were evident across all demographics, with children at the highest risk, mainly due to Cr and smelting industrial sources. Geo-detector and random forest model indicated that spatial disparities in prioritized control elements (Cr and Hg) were primarily influenced by particulate matter (PM10) and anthropogenic activities (industrial and socio-economic factors); variations in particulate matter (PM10 and PM2.5) and meteorological factors (wind speed and precipitation) were the primary controllers of seasonal disparities of Cr and Hg.

Duodenal Soft Tissue Sarcoma with GLI1 Gene Rearrangement: A Case Report and Literature Review.

BACKGROUND Soft tissue tumors have various subtypes, among which sarcomas exhibit high malignant potential and poor prognosis. Malignant epithelioid tumor with GLI1 alterations was originally found in myopericytoma with t(7;12) translocation. However, recent studies indicated that it is a distinct tumor type characterized by multiple nodular distributions of oval or round epithelioid cells with a rich capillary network and a lack of specific immunophenotype. There are only a few cases reported worldwide and the optimal treatment is still being explored. CASE REPORT We report the case of a 31-year-old patient who presented with severe anemia and a large soft tissue mass in the duodenum. The patient underwent surgical resection with a negative margin, and none of the 15 lymph nodes tested positive for the tumor. Postoperative pathology and FISH testing further confirmed the presence of GLI1 disruption and S-100 and SMA negativity. Genetic testing revealed the ACTB-GLI1 fusion. No specific medication was offered after the surgery. No tumor recurrence was found during the 23-month follow-up period. The patient's quality of life is currently satisfactory. CONCLUSIONS Soft tissue sarcomas characterized by GLI1 gene rearrangement have a relatively less aggressive and metastatic nature, with the solid mass spreading minimally even as it grows. Patients can benefit from surgical resection, resulting in a relatively long period of tumor-free survival.

Biochemical and microstructural determinants of the development of serous retinal detachment secondary to retinal vein occlusion.

Purpose: To study the alteration of cytokine factors in aqueous humor and retinal microstructure in the formation of serous retinal detachment (SRD) secondary to retinal vein occlusion. Methods: The subjects were 39 patients with RVO, of whom 31 patients had SRD (RVO-SRD). Spectral Domain Optical Coherence Tomography (SD-OCT) was used to measure the completeness of photoreceptor inner segment/outer segment (IS/OS) and the external limiting membrane (ELM) as well as the structure of RVO-SRD, including the height and shape of SRD. The aqueous humor was collected before intravitreal injection of Ranibizumab. The concentrations of VEGF, MCP-1, IL-8, IL-6, b-FGF and TNF-α in the aqueous humor were measured. All patients participated in the 6-month follow-up examinations, which included visual acuity, intraocular pressure, ophthalmologic examination, and SD-OCT. The time of recurrence of RVO-SRD was recorded. Results: The formation of SRD was associated with the area of congested vein, disrupted IS/OS, ELM layers and high VEGF, MCP-1, IL-8, IL-6 levels. However, the height and shape of SRD were not relevant to any inflammatory factors. Moreover, high levels of MCP-1, IL-8 and IL-6 were found in large areas of congested veins. High levels of MCP-1 and IL-6 were observed in the patients with incomplete IS/OS and ELM. The recurrence of SRD was related to the high MCP-1 level. Conclusion: High concentrations of cytokine factors in aqueous humor could induce vascular leakage, exacerbate the extent of macular edema, disrupt the structure of ELM and IS/OS, and develop SRD in RVO.

The expression mechanism of programmed cell death 1 ligand 1 and its role in immunomodulatory ability of mesenchymal stem cells.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Cost-effectiveness of first-line immunotherapy for advanced non-small cell lung cancer with different PD-L1 expression levels: A comprehensive overview.

BACKGROUND: Immunotherapies can substantially improve treatment efficacy, despite their high cost. A comprehensive overview of the cost-effectiveness analysis (CEA) of immune checkpoint inhibitors (ICIs) in patients with non-small cell lung cancer based on different tumor proportion scores (TPSs) was conducted. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Health Technology Assessment Database, and NHS Economic Evaluation databases were searched from their inception until August 24, 2022. Data relevant to the CEA results were recorded, and quality assessments conducted based on the Quality of Health Economic Studies (QHES) process. FINDINGS: Fifty-one original studies from seven countries were included. The mean QHES score was 77.0 (range: 53-95). Twenty-seven studies were classified as high-quality, and the rest as fair quality. Pembrolizumab, nivolumab, ipilimumab, atezolizumab, camrelizumab, cemiplimab, sintilimab, tislelizumab, and durvalumab were identified using three TPS categories. While nivolumab plus ipilimumab and pembrolizumab plus chemotherapy were unlikely to be cost-effective in China, the results for the US were uncertain. Atezolizumab combinations were not cost-effective in China or the US, and tislelizumab and sintilimab were cost-effective in China. For TPSs ≥ 50%, the pembrolizumab monotherapy could be cost-effective in some developed countries. Cemiplimab was more cost-effective than chemotherapy, pembrolizumab, and atezolizumab in the US. For TPSs ≥ 1%, the cost-effectiveness of pembrolizumab was controversial due to the different willingness-to-pay thresholds. CONCLUSIONS: None of the atezolizumab combination regimens were found to be cost-effective in any perspective of evaluations. Camrelizumab, tislelizumab, and sintilimab have lower ICERs compared to atezolizumab, pembrolizumab, and nivolumab in China. Cemiplimab may be a more affordable alternative to pembrolizumab or atezolizumab. However, it remains unclear which ICIs are the best choices for each country. Future CEAs are required to select comprehensive regimens alongside randomized trials and real-world studies to help verify the economics of ICIs in specific decision-making settings.

Hypothetical chloroplast reading frame 51 encodes a photosystem I assembly factor in cyanobacteria.

Hypothetical chloroplast open reading frames (ycfs) are putative genes in the plastid genomes of photosynthetic eukaryotes. Many ycfs are also conserved in the genomes of cyanobacteria, the presumptive ancestors of present-day chloroplasts. The functions of many ycfs are still unknown. Here, we generated knock-out mutants for ycf51 (sll1702) in the cyanobacterium Synechocystis sp. PCC 6803. The mutants showed reduced photoautotrophic growth due to impaired electron transport between photosystem II (PSII) and PSI. This phenotype results from greatly reduced PSI content in the ycf51 mutant. The ycf51 disruption had little effect on the transcription of genes encoding photosynthetic complex components and the stabilization of the PSI complex. In vitro and in vivo analyses demonstrated that Ycf51 cooperates with PSI assembly factor Ycf3 to mediate PSI assembly. Furthermore, Ycf51 interacts with the PSI subunit PsaC. Together with its specific localization in the thylakoid membrane and the stromal exposure of its hydrophilic region, our data suggest that Ycf51 is involved in PSI complex assembly. Ycf51 is conserved in all sequenced cyanobacteria, including the earliest branching cyanobacteria of the Gloeobacter genus, and is also present in the plastid genomes of glaucophytes. However, Ycf51 has been lost from other photosynthetic eukaryotic lineages. Thus, Ycf51 is a PSI assembly factor that has been functionally replaced during the evolution of oxygenic photosynthetic eukaryotes.

Erratum: Author correction to 'Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice' [Acta Pharmaceutica Sinica B 13 (2023) 1164-1179].

[This corrects the article DOI: 10.1016/j.apsb.2022.10.016.].

Source-specific probabilistic risk evaluation of potentially toxic metal(loid)s in fine dust of college campuses based on positive matrix factorization and Monte Carlo simulation.

Contamination, hazard level and source of 10 widely concerned potentially toxic metal(loid)s (PTMs) Co, As, Pb, Cr, Cu, Zn, Ni, Mn, Ba, and V in fine dust with particle size below 63 µm (FD63) were investigated to assess the environmental quality of college campuses and influencing factors. PTMs sources were qualitatively analyzed using statistical methods and quantitatively apportioned using positive matrix factorization. Probabilistic contamination degrees of PTMs were evaluated using enrichment factor and Nemerow integrated enrichment factor. Eco-health risk levels of content-oriented and source-oriented for PTMs were evaluated using Monte Carlo simulation. Mean levels of Zn (643.8 mg kg-1), Pb (146.0 mg kg-1), Cr (145.9 mg kg-1), Cu (95.5 mg kg-1), and Ba (804.2 mg kg-1) in FD63 were significantly larger than soil background values. The possible sources of the concerned PTMs in FD63 were traffic non-exhaust emissions, natural source, mixed source (auto repair waste, paints and pigments) and traffic exhaust emissions, which accounted for 45.7%, 25.4%, 14.5% and 14.4% of total PTMs contents, respectively. Comprehensive contamination levels of PTMs were very high, mainly caused by Zn pollution and non-exhaust emissions. Combined ecological risk levels of PTMs were low and moderate, chiefly caused by Pb and traffic exhaust emissions. The non-cancer risks of the PTMs in FD63 to college students fell within safety level, while the carcinogenic PTMs in FD63 had a certain cancer risks to college students. The results of source-specific health risk assessment indicated that Cr and As were the priority PTMs, and the mixed source was the priority pollution source of PTMs in FD63 from college campuses, which should be paid attention to by the local government.

Source-specific risk judgement and environmental impact of potentially toxic elements in fine road dust from an integrated industrial city, North China.

The contamination of potentially toxic elements (PTEs) in road dust of large industrial cities is extremely serious. Determining the priority risk control factors of PTE contamination in road dust is critical to enhance the environmental quality of such cities and mitigate the risk of PTE pollution. The Monte Carlo simulation (MCS) method and geographical models were employed to assess the probabilistic pollution levels and eco-health risks of PTEs originating from different sources in fine road dust (FRD) of large industrial cities, and to identify key factors affecting the spatial variability of priority control sources and target PTEs. It was observed that in FRD of Shijiazhuang, a typical large industrial city in China, more than 97% of the samples had an INI > 1 (INImean = 1.8), indicating moderately contaminated with PTEs. The eco-risk was at least considerable (NCRI >160) with more than 98% of the samples, mainly caused by Hg (Ei (mean) = 367.3). The coal-related industrial source (NCRI(mean) = 235.1) contributed 70.9% to the overall eco-risk (NCRI(mean) = 295.5) of source-oriented risks. The non-carcinogenic risk of children and adults are of less importance, but the carcinogenic risk deserves attention. The coal-related industry is a priority control pollution source for human health protection, with As corresponding to the target PTE. The major factors affecting the spatial changes of target PTEs (Hg and As) and coal-related industrial sources were plant distribution, population density, and gross domestic product. The hot spots of coal-related industrial sources in different regions were strongly interfered by various human activities. Our results illustrate spatial changes and key-influencing factors of priority source and target PTEs in Shijiazhuang FRD, which are helpful for environmental protection and control of environmental risks by PTEs.

Causal relationship between nonalcoholic fatty liver disease and different sleep traits: a bidirectional Mendelian randomized study.

Background and aims: Non-alcoholic fatty liver disease(NAFLD) is common worldwide and has previously been reported to be associated with sleep traits. However, it is not clear whether NAFLD changes sleep traits or whether the changes in sleep traits lead to the onset of NAFLD. The purpose of this study was to investigate the causal relationship between NAFLD and changes in sleep traits using Mendelian randomization. Methods: We proposed a bidirectional Mendelian randomization (MR) analysis and performed validation analyses to dissect the association between NAFLD and sleep traits. Genetic instruments were used as proxies for NAFLD and sleep. Data of genome-wide association study(GWAS) were obtained from the center for neurogenomics and cognitive research database, Open GWAS database and GWAS catalog. Three MR methods were performed, including inverse variance weighted method(IVW), MR-Egger, weighted median. Results: In total,7 traits associated with sleep and 4 traits associated with NAFLD are used in this study. A total of six results showed significant differences. Insomnia was associated with NAFLD (OR(95% CI)= 2.25(1.18,4.27), P = 0.01), Alanine transaminase levels (OR(95% CI)= 2.79(1.70, 4.56), P =4.71×10-5) and percent liver fat(OR(95% CI)= 1.31(1.03,1.69), P = 0.03). Snoring was associated with percent liver fat (1.15(1.05,1.26), P =2×10-3), alanine transaminase levels (OR(95% CI)= 1.27(1.08,1.50), P =0.04).And dozing was associated with percent liver fat(1.14(1.02,1.26), P =0.02).For the remaining 50 outcomes, no significant or definitive association was yielded in MR analysis. Conclusion: Genetic evidence suggests putative causal relationships between NAFLD and a set of sleep traits, indicating that sleep traits deserves high priority in clinical practice. Not only the confirmed sleep apnea syndrome, but also the sleep duration and sleep state (such as insomnia) deserve clinical attention. Our study proves that the causal relationship between sleep characteristics and NAFLD is the cause of the change of sleep characteristics, while the onset of non-NAFLD is the cause of the change of sleep characteristics, and the causal relationship is one-way.

Circ-SHPRH in human cancers: a systematic review and meta-analysis.

Circular RNA (circRNA) molecules are noncoding RNAs with ring-like structures formed by covalent bonds and are characterized by no 5'caps or 3'polyadenylated tails. Increasing evidence shows that circRNAs may play an important role in tumorigenesis and cancer metastasis. Circ-SHPRH originates from exons 26-29 of the SHPRH gene, and it is closely associated with human cancers. We searched PubMed, Web of Science, and Embase databases for relevant literatures until 24 December 2022. Eighteen research papers were included in this review, and 11 papers were selected for meta-analysis after screening. Three eligible published studies about circ-SHPRH were enrolled based on their tumor diagnosis aspect, 7 eligible published studies were related to overall survival (OS), and 3 eligible published studies were related to tumor grade. Many studies have shown that circ-SHPRH acts as a miRNA sponge or encodes a protein to regulate downstream genes or signal pathways, and exerts specific biological functions that affect the proliferation, invasion, and apoptosis of cancer cells. Meta-analysis showed that patients with high expression of circ-SHPRH had better OS (HR = 0.53, 95% CI 0.38-0.74, p-value <0.05) and lower TNM stage (HR = 0.33, 95% CI 0.18-0.62, p-value = 0.001). In addition, circ-SHPRH has potential diagnostic value (AUC = 0.8357). This review will help enrich our understanding of the role and mechanism of circ-SHPRH in human cancers. Circ-SHPRH has the potential to be a novel diagnostic and prognostic biomarker for various solid cancers.

Therapeutic potential of icariin in rats with letrozole and high-fat diet-induced polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is characterized by reproductive, endocrine, and metabolic disorders. Icariin has been shown to regulate endocrine and metabolic imbalances. This study aimed to determine the therapeutic effect and pharmacological mechanism of icariin in PCOS rats. Rats were fed a high-fat diet and gavaged with letrozole to induce PCOS. Thirty-six female rats were randomly divided into four groups: control, model, low-dose, and high-dose icariin. After 30 days of treatment, we evaluated the therapeutic effects on weight and diet, sex hormone levels, ovarian morphology, estrous cycle, inflammatory factors, and indicators of glucolipid metabolism. Combined with the ovarian transcriptome, we verified the key markers of apoptosis and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway by RT-qPCR for mRNA level, western blot, and immunohistochemistry for protein expression. Icariin significantly improved ovarian function and reproductive endocrine disorders by regulating sex hormones, restoring the estrous cycle, and reducing ovarian morphological damage in PCOS rats. Icariin-treated rats had lower weight gain and reduced triglycerides, fasting insulin, HOMA-IR, TNF-α, and interleukin-6 with higher high-density lipoprotein cholesterol levels than PCOS rats. TUNEL staining showed icariin improved apoptosis in the ovaries. This was supported by an increase in Bcl2 and a decrease in Bad and Bax. Icariin decreased the ratios of p-JAK2/JAK2, p-STAT1/STAT1, p-STAT3/STAT3, and p-STAT5a/STAT5a, decreased IL-6, gp130 expression, and increased cytokine-inducible SH2-containing protein (CISH) and suppressor of cytokine signaling 1 (SOCS1) expression. The pharmacological mechanism may be related to the reduction in ovarian apoptosis and inhibition of the IL-6/gp130/JAK2/STATs pathway.

Potentially toxic elements in surface fine dust of residence communities in valley industrial cities.

A comprehensive analysis of content, pollution characteristics, health hazard, distribution, and source of some broadly concerned potentially toxic elements (PTEs, Pb, V, Mn, Cr, Ba, Zn, Ni, and Cu) in surface fine dust with particle size <63 µm (SFD63) from residence communities in Xi'an, a representative valley industrial city, was conducted in this research to analyze the quality of environment and influencing factors of valley industrial cities in China. The average contents of Ba (794.1 mg kg-1), Cu (61.3 mg kg-1), Pb (99.9 mg kg-1), Zn (408.1 mg kg-1), Cr (110.0 mg kg-1), and Ni (33.4 mg kg-1) in SFD63 of Xi'an residence communities surpassed their background contents of local soil. The high enrichment-value regions of PTEs were chiefly located in the regions with high traffic flow, high population density, and areas around industries. Zn and Pb had moderate enrichment, and the overall pollution level of PTEs was unpolluted-to-moderate and moderate pollution. Three source categories (including natural geogenic source, industrial anthropogenic source, and mixed anthropogenic source of transportation, residential activities, and construction) were identified as the predominant sources for the PTEs pollution in SFD63, with the contribution levels of 29.9%, 32.4%, and 37.7%, respectively. The assessment of health risks according to Monte Carlo simulation revealed that the 95% of the non-cancer risk of PTEs to residents (the elderly, working people, and children) was less than the threshold of 1, while the probability of cancer risk exceeding the acceptable threshold of 1E-6 was 93.76% for children, 68.61% for the elderly, and 67.54% for working people. Industrial source was determined as priority pollution source and Cr was determined as priority pollutant, which should be concerned.

Characteristics and Trends in Clinical Trials of Cardiovascular Drugs in China from 2009 to 2021.

BACKGROUND: Cardiovascular disease remains the leading cause of death worldwide and brings a heavy burden. However, the development of cardiovascular drug clinical trials in China remains unclear. The purpose of this study was to identify the status of clinical trials of cardiovascular drugs in China and provide a reference for stakeholders' decisions. METHODS: Data were collected from the National Medical Products Administration (NMPA) Registration and Information Disclosure Platform for Drug Clinical Trials before July 1, 2021. We collected all information about clinical trials, including study design, and leading unit. The landscape of cardiovascular drug clinical trials was analyzed by the characteristics, time trends, indications, and geographical distribution. RESULTS: A total of 1666 cardiovascular drug clinical trials were launched from 2009 to 2021 in China. Bioequivalence/bioavailability studies accounted for the most significant proportion (1099 [65.97%]), followed by phase I (296 [17.77%]), phase III (135 [8.10%]), phase II (118 [7.08%]), and phase IV trials (18 [1.08%]). Initiated trials increased by 23.45% annually from 2009 to 2020. Trials of hypertension accounted for the most significant number, followed by coronary heart disease, dyslipidemia, and heart failure. Most trials (66.68%) were conducted in eastern China, followed by the central and western regions, showing a regional disparity as leading units. CONCLUSION: Despite the significant progress of cardiovascular drug clinical trials in China, there is still a long way to innovative drug research and development, requiring persistent policy support and more investment. Innovation, quality, efficiency, and equity need to be carefully considered by all stakeholders in clinical trials.

Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury via increasing the gut microbiota Lactobacillus johnsonii and regulating macrophage anti-inflammatory activity in mice.

Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of Panax ginseng C. A. Meyer, Lilium brownie F. E. Brown ex Miellez var. viridulum Baker, Polygonatum sibiricum Delar. ex Redoute, Lonicera japonica Thunb., Hippophae rhamnoides Linn., Amygdalus Communis Vas, Platycodon grandiflorus (Jacq.) A. DC., and Cortex Phelloderdri. Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of Lactobacillus johnsonii (L. johnsonii) in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, L. johnsonii significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10+ M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation L. johnsonii (HI-L. johnsonii) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota L. johnsonii as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, via L. johnsonii-dependent immune regulation and interleukin-10+ M2 macrophage production.

Effects of sericin and egg white on the inflammation of damaged skin in mice.

Sericin and egg white (EW) have shown the ability to promote wound healing. However, there have been insufficient studies regarding the effects of sericin and EW mixtures on wound healing. This study aimed to investigate the effects of a hybrid sericin and EW solution on wound repair and inflammation-related indicators in mouse skin. In this work, sericin with a low molecular weight was first mixed with homogeneous EW to prepare a hybrid wound dressing. Histology evaluation, the expression of C-reactive protein (CRP) and inflammatory cytokines in mice were tested to determine the effects of this dressing on skin injuries in mice. The results showed that sericin and the hybrid solution of sericin and EW effectively promoted wound healing in mouse skin. The wound recovery rates of mice 12 days after treatment with a medium dose of sericin (0.2 g ml-1) and the same dosage of sericin with added EW were 1.32 and 1.65 times that of mice treated with phosphate buffer saline as a control, respectively. In addition, the mixture solution was more effective in wound healing than sericin alone. Sericin with EW significantly reduced the expression of CRP and inflammatory cytokines in mice during wound healing. A sericin and EW hybrid solution can effectively shorten the time needed for wound healing and reduce inflammation-related indicators in mice, making it a promising candidate for wound dressing.

Icariin Alleviates Nonalcoholic Fatty Liver Disease in Polycystic Ovary Syndrome by Improving Liver Fatty Acid Oxidation and Inhibiting Lipid Accumulation.

(1) Background: Icariin is the main component of the Chinese herb Epimedium. A number of studies have shown that it alleviates abnormal lipid metabolism. However, it is not clear whether and how icariin can ameliorate hepatic steatosis with polycystic ovary syndrome (PCOS). This study was designed to explore the anti-hepatosteatosis effect of icariin in rats with polycystic ovary syndrome. (2) Methods: Female Sprague Dawley(SD)rats were treated with a high-fat diet and letrozole for 21 days to make nonalcoholic fatty liver disease (NAFLD) in the polycystic ovary syndrome model. Then model rats were treated with icariin (by gavage, once daily) for 28 days. Serum hormones and biochemical variables were determined by ELISA or enzyme. RNA-sequence analysis was used to enrich related target pathways. Then, quantitative Real-time PCR (qRT-PCR) and Western blot were performed to verify target genes and proteins. (3) Results: Icariin treatment reduced excess serum levels of Testosterone (T), Estradiol (E2), Luteinizing hormone (LH), Follicle-stimulating hormone (FSH), LH/FSH ratio, insulin, triglycerides (TG), and aspartate aminotransferase (AST) in high-fat diet (HFD) and letrozole fed rats. Meanwhile, icariin ameliorated HFD and letrozole-induced fatty liver, as evidenced by a reduction in excess triglyceride accumulation, vacuolization, and Oil Red O staining area in the liver of model rats. Results of RNA-sequencing, western blotting, and qRT-PCR analyses indicated that icariin up-regulated fatty acid translocase (CD36), in mitochondria, and peroxisome proliferator-activated receptor α (PPARα) expression, which led to the enhancement of fatty acid oxidation molecules, such as cytochrome P450, family 4, subfamily a, polypeptide 3 (CYP4A3), carnitine palmitoyltransferase 1 α (CPT1α), acyl-CoA oxidase 1 (ACOX1), medium-chain acyl-CoA dehydrogenase (MCAD), and long-chain acyl-CoA dehydrogenase (LCAD). Besides, icariin reduced lipid synthesis, which elicited stearoyl-Coenzyme A desaturase 1 (SCD1), fatty acid synthase (FASN), and acetyl-CoA (ACC). (4) Conclusion: Icariin showed an ameliorative effect on hepatic steatosis induced by HFD and letrozole, which was associated with improved fatty acid oxidation and reduced lipid accumulation in the liver.