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Pei Zhang,1,* Tian-Yu Wang,2,* Zi-Yue Luo,2 Jun-Can Ding,2 Qiang Yang,2 Peng-Fei Hu3 1Department of Cardiology, Sir Run Run Shaw Hospital, College of Medicine Zhejiang University, Hangzhou, Zhejiang Province, 310018, People’s Republic of China; 2Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310053, People’s Republic of China; 3Department of Cardiology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China*These authors contributed equally to this workCorrespondence: Peng-Fei Hu, Department of Cardiology, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, 310005, People’s Republic of China, Tel +86 15267037741, Email 20064012@zcmu.edu.cnPurpose: Heart failure is a serious complication after acute myocardial infarction (AMI). It is crucial to investigate the mechanism of action of empagliflozin in the treatment of heart failure.Methods: A total of 20 wild type (WT) male C57BL6/J mice were used to establish a model of heart failure after myocardial infarction and randomly divided into 2 groups: treatment group and control group. The treatment group was treated with empagliflozin, and the control group was treated with placebo. After 8 weeks of treatment, mouse heart tissues were collected for next generation sequencing. Bioinformatics methods were used to screen the key genes. Finally, the correlation between clinical data and gene expression was analyzed. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression of key genes.Results: A mouse model of heart failure was successfully constructed. By DEG analysis, a total of 740 DEGs in the treatment group vs the control group were obtained. Dendritic cells, granulocytes, follicular B, plasma cell, cDC1, cDC2, pDC and neutrophils were 8 different immune cells identified by immunoinfiltration analysis. Through WGCNA, the turquoise module with the highest correlation with the above differential immune cells was selected. One hundred and forty-two immune-related DEGs were obtained by taking intersection of the DEGs and the genes of the turquoise module. Col17a1 and Gria4 were finally screened out as key immune-related genes via PPI analysis and machine learning. Col17a1 was significantly up-regulated, while Gria4 was significantly down-regulated in the treatment group. At the same time, the expression level of Col17a1 was significantly correlated with left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS) and left ventricular internal dimension systole (LVIDs).Conclusion: Col17a1 and Gria4 are key immune-related genes of empagliflozin in the treatment of heart failure after myocardial infarction. This study provides a scientific basis for elucidating the mechanism of action of empagliflozin in treating heart failure after myocardial infarction.Keywords: heart failure after myocardial infarction, empagliflozin, immunology, RNA-seq

Ting Xia,1– 3 Xiao Liang,4 Chang-Shun Liu,1– 3 Yan-Nan Hu,1– 3 Zhen-Ye Luo,1– 3 Xiao-Mei Tan1– 3 1School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Chinese Medicine Pharmaceutics, Southern Medical University, Guangzhou, 510515, People’s Republic of China; 3Guangdong Provincial Engineering Laboratory of Chinese Medicine Preparation Technology, Guangzhou, 510515, People’s Republic of China; 4School of Pharmaceutical Sciences, Guilin Medical University, Guilin, 541199, People’s Republic of ChinaCorrespondence: Xiao-Mei Tan, Tel/Fax + 86-020-61648265, Email tanxm_smu@163.comBackground: Ermiao Wan (EMW) is commonly used to treat atopic dermatitis (AD) in China. However, the pharmacological mechanisms underlying the action of EMW against AD remain unclear.Purpose: We aimed to determine the mechanisms underlying the effectiveness of EMW in the treatment of AD.Methods: We evaluated the effect of EMW on AD induced by dinitrochlorobenzene (DNCB) in BALB/C mice. To clarify the key components of EMW in AD treatment, the main components of EMW were identified using HPLC. Serum pharmacochemistry was used to analyze the absorbed ingredients from blood. Based on the phytochemical results, network pharmacology and molecular docking were used to predict the action of EMW. Skin transcriptomic analysis was used to validate the network pharmacology results. RT-qPCR,ELISA, and immunohistochemical were performed to validate the results of skin transcriptomics.Results: EMW improved the symptoms of AD, with less rashes, less spontaneous scratching, less inflammatory cell infiltration, and fewer allergic reactions. The established HPLC method is simple and reliable. Chlorogenic acid, phellodendrine, magnoflorine, jatrorrhizine, palmatine, berberine, and atractylodin were the key effective ingredients with a high blood concentration. Fifty-seven primary causal targets of EMW against AD were identified. These targets are mainly involved in ErbB signaling pathways including EGFR, AKT1, MAPK8, JUN, MAPK1. Molecular docking showed that EGFR, AKT1, MAPK8, JUN, MAPK1 had good binding force with EMW. In AD mice, EMW regulated the EGFR/AKT signaling through upregulation of Grb2, GAB1, Raf-1, EGFR, and AKT, and downregulation of MAPK1 and JUN, compared to that in the MD group.Conclusion: EMW could alleviate AD through activating EGFR/AKT signaling and suppressing MAPK. This study provides a theoretical basis for the clinical use of EMW.Keywords: Ermiao Wan, atopic dermatitis, network pharmacology, serum pharmacochemistry, skin transcriptome, EGFR/AKT signaling

Chun-Yang Wang,1,2 Shu Liu,1,2 Xiao-Nv Xie,1,2 Zhi-Ying Luo,1,2 Li Yang,1,2 Zhi-Rong Tan1,2 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, People’s Republic of China; 2Department of Clinical Pharmacology, Institute of Clinical Pharmacology, Central South University; Hunan Key Laboratory of Pharmacogenetics, Changsha 410078, People’s Republic of China Introduction: The small peptide transporter 1 (PepT-1) and adipose phospholipase A2 (AdPLA) play a key role in the development of obesity. However, there are no data assessing the impact of PepT-1 (SLC15A1) and AdPLA (PLA2G16) variants on obesity susceptibility. Therefore, we assessed the contribution of 9 single-nucleotide polymorphisms (SNPs) between these two genes on obesity susceptibility in Chinese subjects.Materials and methods: A total of 611 participants were enrolled in the study, and 9 SNPs in the SLC15A1 and PLA2G16 genes were selected. Blood samples were collected for genotyping. Overweight and obesity were established by body mass index. Regression analyses were performed to test for any association of genetic polymorphisms with weight abnormality.Results: The genotype frequencies (P=0.04 for rs9557029, P=0.027 for rs1289389) were significantly different between obese or overweight subjects and healthy controls. However, no significant difference in allele was found between these three groups (P>0.05). Further logistic regression analyses adjusted for age and sex also failed to reveal significant associations between overweight, obesity, and the selected SNPs (P>0.05).Conclusion: Data indicate that the selected 9 SNPs in SLC15A1 and PLA2G16 genes were not related to obesity susceptibility in the Han Chinese population. Keywords: obesity, BMI, Chinese subjects, genotyping, SNPs

Hai-Fei Chen,1,2 Li-Ping Xu,1 Zhi-Yong Luo,1 Zi-Qiang Yu,2 Zheng-Yang Li,1 Qing-Ya Cui,1 Long-Mei Qin,1 Yong-Ya Ren,1 Hong-Shi Shen,1 Jie-Qing Tang,1 Ling-Juan Jin,1 Jing-Jing Zhu,1 Jing Wang,1 Ke-Yuan Wang,1 Tian-Qin Wu,1 Zhao-Yue Wang21Department of Hematology, 100th Hospital of People's Liberation Army, 2Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of ChinaAbstract: A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.Keywords: side effect, hypofibrinogenemia, cerebral hemorrhage, cerebellopontine angle, neoplasm

Objective: This study evaluates the risk of ocular adverse events (AEs) associated with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) using data from the FDA Adverse Event Reporting System (FAERS) and network pharmacology methods., Methods: FAERS data from 2004 to 2024 were analyzed for ocular AEs linked to GLP-1 RA treatments. Disproportionality analysis (Reporting Odds Ratio, ROR) was used to identify signals, and a drug-gene interaction network explored potential mechanisms., Results: Among 17,785,793 FAERS reports, semaglutide and lixisenatide were significantly associated with ocular AEs, with RORs of 1.25 (95% CI, 1.20-1.31) and 1.96 (95% CI, 1.70-2.27), respectively. Commonly reported AEs included blurred vision, visual impairment, and diabetic retinopathy, with some AEs occurring as early as 10 days after treatment initiation. Gene enrichment analysis highlighted potential links between GLP-1-related genes and ocular AEs., Conclusion: The widespread use of GLP-1 RAs has raised concerns regarding their ophthalmic safety. This study contributes new evidence from real-world data, suggesting that semaglutide and lixisenatide are associated with significant risks of ocular AEs. Further experimental studies are warranted to elucidate the underlying mechanisms and confirm these associations.

Objectives: To investigate the prevalence of tension-type headache (TTH) in children and adolescents aged 0-19 years globally in 1990-2021, and to provide a basis for the prevention and treatment of TTH., Methods: Based on the Global Burden of Disease Study data, the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years, with different sexes, age groups, sociodemographic index (SDI) regions and countries/territories., Results: The age-standardized prevalence rate (ASPR) of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000, which was increased by 1.73% since 1990. The ASPR in females was slightly higher than that in males (1990: 17 707.65/100 000 vs 16 403.78/100 000; 2021: 17 946.29/100 000 vs 16 763.09/100 000). The ASPR in adolescence was significantly higher than that in school-aged and preschool periods (1990: 27 672.04/100 000 vs 10 134.16/100 000; 2021: 28 239.04/100 000 vs 10 059.39/100 000). Regions with high SDI exhibited a higher ASPR than the other regions, with significant differences in prevalence rates across different countries. From 1990 to 2021, there was a slight increase in global ASPR, with an average annual percentage change (AAPC) of 0.06%. Females experienced a smaller increase than males based on AAPC (0.04% vs 0.07%). There was reduction in ASPR in preschool and school-aged groups, with an AAPC of -0.02%, while there was a significant increase in ASPR in adolescence, with an AAPC of 0.07%. ASPR decreased in regions with low-middle and low levels of SDI, with an AAPC of -0.02% and -0.04%, respectively, while it increased in regions with middle SDI, with an AAPC of 0.24%., Conclusions: There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally, with significant differences across sexes, age groups, SDI regions and countries/territories.

Background: In China, both percutaneous microwave/radiofrequency ablation liver partition plus portal vein embolization (PALPP) and transarterial chemoembolization (TACE) plus portal vein embolization (PVE) have been utilized in planned hepatectomy. However, there is a lack of comparative studies on the effectiveness of these two techniques for cases with insufficient future liver remnant (FLR)., Methods: Patients were categorized into either the PALPP group or the TACE + PVE group. Clinical data, including FLR growth rate, complications, secondary resection rate, and overall survival rate, were compared and analyzed for both groups retrospectively., Results: Between December 2014 and October 2021, a total of 29 patients underwent TACE + PVE (n = 12) and PALPP (n = 17). In the TACE + PVE group, 7 patients successfully underwent two-stage hepatectomy, while in the PALPP group, 13 patients underwent the procedure (two-stage resection rate: 58.3% vs. 76.5%, P = 0.42). There were no significant differences in postoperative complications of one-stage procedures (11.8% vs. 8.3%, P > 0.05) and second-stage resection complication (0% vs. 46.2%, P = 0.05) between the TACE + PVE and PALPP groups. However, the PALPP group demonstrated a shorter time to FLR volume growth for second-stage resection (18.5 days vs. 66 days, P = 0.001) and KGR (58.5 ml/week vs. 7.7 ml/week, P = 0.001)., Conclusions: Compared with TACE + PVE, PALPP results in a more significant increase in FLR volume and a higher rate of two-stage resection without increasing postoperative complications., (© 2024. The Author(s).)

Based on the differences in targeted energy metabolomics, intestinal barrier protein expression, and glucose transport,the synergistic mechanism of Coptidis Rhizoma(CR) processed with Euodiae Fructus(ECR) on ulcerative colitis(UC) was explored.Mice were administered 4% dextran sulfate sodium to induce UC model, and then randomly divided into a model group, a CR group,and an ECR group. After 14 days of treatment, the therapeutic effect of processing on UC was assessed through histopathology of colon tissue and inflammatory indexes. Targeted energy metabolomics analysis was performed to evaluate the effect of processing on colon tissue energy metabolism. Molecular docking was carried out to predict the binding affinity of energy metabolites with intestinal barrier tight junction protein Claudin and glucose transporter 2(GLUT2). In vivo unidirectional intestinal perfusion experiments in rats were conducted to evaluate the effect of processing on intestinal glucose transport. The results showed that both CR and ECR could repair colon tissue damage in UC mice, downregulate tissue inflammatory factors interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α)levels, with the efficacy of ECR being superior to CR. Processed products significantly upregulated levels of multiple metabolites in colon tissue glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation, among which the upregulated levels of 1,6-diphosphate fructose and acetyl coenzyme A could bind well with Claudin and GLUT2. Additionally, the processed product also increased the expression of GLUT2 and enhanced glucose transport activity. This study suggests that ECR may enhance glucose transport to improve colon energy metabolism, promote barrier repair, and exert synergistic effects through processing.

Background: With the improvements in laparoscopic or robotic surgical techniques and instruments, a growing number of surgeons have attempted to complete all digestive tract reconstruction intracorporeally; these procedures include totally robotic gastrectomy (TRG) and totally laparoscopic gastrectomy (TLG). This study aimed to evaluate the safety and feasibility of the TRG and compare the short-term outcomes of the TRG and TLG in patients with gastric cancer., Methods: Between January 2018 and June 2023, 346 consecutive patients who underwent TRG or TLG at a high-volume academic gastric cancer specialty center were included. 1:1 propensity score matching (PSM) was performed to reduce confounding bias. The surgical outcomes, postoperative morbidity, and surgical burden were compared in PSM cohort., Results: After PSM, a well-balanced cohort of 194 patients (97 in each group) was included in the analysis. The total operation time of the TRG group was significantly longer than that of the TLG group (244.9 vs. 213.0 min, P < 0.001). There was no significant difference in the effective operation time between the 2 groups (217.8 vs. 207.2 min, P = 0.059). The digestive tract reconstruction time of the TRG group was significantly shorter than that of the TLG group (39.4 vs. 46.7 min, P < 0.001). The mean blood loss in the TRG group was less than that in the TLG group (101.1 vs. 126.8 mL, P = 0.014). The TRG group had more retrieved lymph nodes in the suprapancreatic area than that in the TLG group (16.6 vs 14.2, P = 0.002). The TRG group had a lower surgery task load index (38.9 vs. 43.1, P < 0.001) than the TLG group. No significant difference was found in terms of postoperative morbidity between the 2 groups (14.4% vs. 16.5%, P = 0.691)., Conclusion: This study demonstrated that TRG is a safe and feasible procedure, and is preferable to TLG in terms of invasion and ergonomics. The TRG may maximize the superiority of robotic surgical systems and embodies the theory of minimally invasive surgery., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: To determine the prevalence of anxiety and depression in patients with nasopharyngeal carcinoma (NPC) and to identify central symptoms and bridge symptoms among psychiatric disorders., Methods: This cross-sectional study recruited patients with NPC in Guangzhou, China from May 2022, to October 2022. The General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) were used for screening anxiety and depression, respectively. Network analysis was conducted to evaluate the centrality and connectivity of the symptoms of anxiety, depression, quality of life (QoL) and insomnia., Results: A total of 2806 respondents with complete GAD-7 and PHQ-9 scores out of 3828 were enrolled. The incidence of anxiety in the whole population was 26.5% (depression, 28.5%; either anxiety or depression, 34.8%). Anxiety was highest at caner diagnosis (34.2%), while depression reached a peak at late-stage radiotherapy (48.5%). Both moderate and severe anxiety and depression were exacerbated during radiotherapy. Coexisting anxiety and depression occurred in 58.3% of those with either anxiety or depression. The generated network showed that anxiety and depression symptoms were closely connected; insomnia was strongly connected with QoL. "Sad mood", "Lack of energy", and "Trouble relaxing" were the most important items in the network. Insomnia was the most significant bridge item that connected symptom groups., Conclusion: Patients with NPC are facing alarming disturbances of psychiatric disorders; tailored strategies should be implemented for high-risk patients. Besides, central symptoms (sad mood, lack of energy, and trouble relaxing) and bridge symptoms (insomnia) may be potential interventional targets in future clinical practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Papillary thyroid carcinoma (PTC) with metastatic lymph nodes (LNs) is closely associated with disease recurrence. This study accessed the value of superb microvascular imaging (SMI) in the diagnosis and prediction of metastatic cervical LNs in patients with PTC., Methods: A total of 183 cervical LNs (103 metastatic and 80 reactive) from 116 patients with PTC were analysed. Metastatic cervical LNs were confirmed by pathology or/and cytology; reactive cervical LNs were confirmed by pathology or clinical features. The characteristic of conventional ultrasound (US) was extracted using univariate and multivariate analyses. The diagnostic performance of US and SMI were compared using the area under the receiver operating curve (AUC) with corresponding sensitivity and specificity. A nomogram was developed to predict metastatic LNs in patients with PTC, based on multivariate analyses., Results: L/S < 2, ill-defined border, absence of hilum, isoechoic or hyperechoic, heterogeneous internal echo, peripheral or mixed vascular pattern on color Doppler flow imaging (CDFI) and SMI, and a larger SMI vascular index appeared more frequently in metastatic LNs in the training datasets than in reactive LNs (P < 0.05). The diagnostic sensitivity, specificity and accuracy of SMI vs US are 94.4% and 87.3%, 79.3% and 69.3%, and 87.6% and 79.1%, respectively; SMI combined with US exhibited a higher AUC [0.926 (0.877-0.975)] than US only [0.829 (0.759-0.900)]. L/S < 2, peripheral or mixed vascular type on CDFI, and peripheral or mixed vascular types on SMI were independent predictors of metastatic LNs with PTC. The nomogram based on these three parameters exhibited excellent discrimination, with an AUC of 0.926., Conclusion: SMI was superior to US in diagnosing metastatic LNs in PTC. US combined with SMI significantly improved the diagnostic accuracy of metastatic cervical LNs with PTC. SMI is efficacious for differentiating and predicting metastatic cervical LNs., (© 2024. The Author(s).)

Background: The incidence of adolescent depression has markedly risen in recent years, with a high recurrence rate into adulthood. Diagnosis in adolescents is challenging due to subjective factors, highlighting the crucial need for objective diagnostic markers., Methods: Our study enrolled 204 participants, including healthy controls (n = 88) and first-episode adolescent depression patients (n = 116). Serum samples underwent gas chromatography-mass spectrometry (GC-MS) analysis to assess non-esterified fatty acids (NEFA) expression. Machine learning and ROC analysis were employed to identify potential biomarkers, followed by bioinformatics analysis to explore underlying mechanisms., Results: Nearly all differentially expressed NEFA exhibited significant downregulation. Notably, nonanoic acid, cis-10-pentadecenoic acid, cis-10-carboenoic acid, and cis-11-eicosenoic acid demonstrated excellent performance in distinguishing adolescent depression patients. Metabolite-gene interaction analysis revealed these NEFAs interacted with multiple genes. KEGG pathway analysis on these genes suggested that differentially expressed NEFA may impact PPAR and cAMP signaling pathways., Limitations: Inclusion of diverse populations for evaluation is warranted. Biomarkers identified in this study require samples that are more in line with the experimental design for external validation, and further basic research is necessary to validate the potential depressive mechanisms of NEFA., Conclusions: The overall reduction in NEFA expression in first-episode adolescent depression patients suggests a potential mediation of depression symptoms through cAMP and PPAR signaling pathways. NEFA levels show promise as a diagnostic tool for identifying first-episode adolescent depression patients., Competing Interests: Declaration of competing interest There is none conflict of interest on this research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The rare fungus Candida saopaulonensis has never been reported to be associated with human infection. We report the draft genome sequence of the first clinical isolate of C. saopaulonensis, which was isolated from a very premature infant with sepsis. This is the first genome assembly reaching the near-complete chromosomal level with structural annotation for this species, opening up avenues for exploring evolutionary patterns and genetic mechanisms of pathogenesis., (© 2024. The Author(s).)

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 μmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Hyperglycemia in pregnancy can increase the risk of congenital disorders, but little is known about craniofacial skeleton malformation and its corresponding medication. Our study first used meta-analysis to review the previous findings. Second, baicalin, an antioxidant, was chosen to counteract high glucose-induced craniofacial skeleton malformation. Its effectiveness was then tested by exposing chicken embryos to a combination of high glucose (HG, 50 mM) and 6 μM baicalin. Third, whole-mount immunofluorescence staining and in situ hybridization revealed that baicalin administration could reverse HG-inhibited neural crest cells (NCC) delamination and migration through upregulating the expression of Pax7 and Foxd3, and mitigate the disordered epithelial-mesenchymal transition (EMT) process by regulating corresponding adhesion molecules and transcription factors (i.e., E-cadherin, N-cadherin, Cadherin 6B, Slug and Msx1). Finally, through bioinformatic analysis and cellular thermal shift assay, we identified the AKR1B1 gene as a potential target. In summary, these findings suggest that baicalin could be used as a therapeutic agent for high glucose-induced craniofacial skeleton malformation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer XL is currently organizing a Research Topic with the author GW. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Lu, Luo, Sun, Wang, Sun, Huang, Yang, Ding and Wang.)

Extensive investigations have been conducted regarding the potential correlation between blood type and the immune system, as well as cancer risk in the Southern Chinese population. However, the prognostic value of the blood group and its genetic determinants in the context of immune checkpoint inhibitor (ICI) treatment remains unclear. Therefore, the associations between the ABO blood group and its single nucleotide polymorphisms (SNPs) were examined in relation to ICI treatment outcomes in 370 eligible patients with cancer. This approach allowed us to derive the blood group from the SNPs responsible for blood group determination. In the discovery cohort (N = 168), antigen A carriers (blood types A and AB) exhibited an extended progression-free survival (PFS; hazard ratio (HR) = 0.58, 95% confidence interval (CI) = 0.34-0.98). The association results from the SNP-derived blood were consistent with those from the measured blood group. In the validation cohort (N = 202), Cox regression analysis revealed that the antigen A carriers (rs507666 AA+GA genotype carriers) experienced significantly extended PFS compared with the non-antigen A carriers (HR = 0.61, 95% CI = 0.40-0.93). Therefore, a longer PFS was observed in antigen A carriers (P value = 0.003, HR = 0.60, 95% CI = 0.44-0.84). Furthermore, haplotype 2 carriers (rs507666 GA and rs659104 GG) demonstrated both extended PFS and improved overall survival. Notably, the presence of antigen A was not associated with the occurrence of overall immune-related adverse events (irAEs) or organ-specific toxicity. In summary, our findings revealed that antigen A carriers did not experience a higher incidence of irAEs while exhibiting better immunotherapy efficacy., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

Objective: To investigate the effects of Pien Tze Huang (PZH) on the migration and invasion of HCC cells and underlying molecular mechanism., Methods: Cell counting kit-8 (CCK-8) was applied to evaluate the cell viabilities of SMMC-7721, SK-Hep-1, C3A and HL-7702 (6 × 10 3 cells/well) co-incubated with different concentrations of PZH (0, 0.2, 0.4, 0.6, 0.8 mg/mL) for 24 h. Transwell, wound healing assay, CCK-8 and Annexin V-FITC/PI staining were conducted to investigate the effects of PZH on the migration, invasion, proliferation and apoptosis of SK-Hep-1 and SMMC-7721 cells (650 µ g/mL for SK-Hep-1 cells and 330 µ g/mL for SMMC-7721 cells), respectively. In vivo, lung metastasis mouse model constructed by tail vein injection of HCC cells was used for evaluating the anti-metastasis function of PZH. SK-Hep-1 cells (10 6 cells/200 µ L per mice) were injected into B-NDG mice via tail vein. Totally 8 mice were randomly divided into PZH and control groups, 4 mice in each group. After 2-d inoculation, mice in the PZH group were administered with PZH (250 mg/kg, daily) and mice in the control group received only vehicle (PBS) from the 2nd day after xenograft to day 17. Transcriptome analysis based on RNA-seq was subsequently used for deciphering anti-tumor mechanism of PZH. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to verify RNA-seq results. Luciferase reporter assay was performed to examine the transcriptional activity of yes-associated protein (YAP)., Results: PZH treatment significantly inhibited the migration, invasion, proliferation and promoted the apoptosis of HCC cells in vitro and in vivo (P<0.01). Transcriptome analysis indicated that Hippo signaling pathway was associated with anti-metastasis function of PZH. Mechanical study showed PZH significantly inhibited the expressions of platelet derived growth factor receptor beta (PDGFRB), YAP, connective tissue growth factor (CCN2), N-cadherin, vimentin and matrix metallopeptidase 2 (MMP2, P<0.01). Meanwhile, the phosphorylation of YAP was also enhanced by PZH treatment in vitro and in vivo. Furthermore, PZH played roles in inhibiting the transcriptional activity of YAP., Conclusion: PZH restrained migration, invasion and epithelial-mesenchymal transition of HCC cells through repressing PDGFRB/YAP/CCN2 axis., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: We explored the epidemiological and molecular characteristics of Candida parapsilosis sensu stricto isolates in China, and their mechanisms of azole resistance., Methods: Azole susceptibilities of 2318 non-duplicate isolates were determined using CLSI broth microdilution. Isolates were genotyped by a microsatellite typing method. Molecular resistance mechanisms were also studied and functionally validated by CRISPR/Cas9-based genetic alterations., Results: Fluconazole resistance occurred in 2.4% (n = 56) of isolates, and these isolates showed a higher frequency of distribution in ICU inpatients compared with susceptible isolates (48.2%, n = 27/56 versus 27.8%, 613/2208; P = 0.019). Microsatellite-genotyping analysis yielded 29 genotypes among 56 fluconazole-resistant isolates, of which 10 genotypes, including 37 isolates, belonged to clusters, persisting and transmitting in Chinese hospitals for 1-29 months. Clusters harbouring Erg11Y132F (5/10; 50%) were predominant in China. Among these, the second most dominant cluster MT07, including seven isolates, characteristically harbouring Erg11Y132F and Mrr1Q625K, lent its carriage to being one of the strongest associations with cross-resistance and high MICs of fluconazole (>256 mg/L) and voriconazole (2-8 mg/L), causing transmission across two hospitals. Among mutations tested, Mrr1Q625K led to the highest-level increase of fluconazole MIC (32-fold), while mutations located within or near the predicted transcription factor domain of Tac1 (D440Y, T492M and L518F) conferred cross-resistance to azoles., Conclusions: This study is the first Chinese report of persistence and transmissions of multiple fluconazole-resistant C. parapsilosis sensu stricto clones harbouring Erg11Y132F, and the first demonstration of the mutations Erg11G307A, Mrr1Q625K, Tac1L263S, Tac1D440Y and Tac1T492M as conferring resistance to azoles., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

This study investigated the differences in excretion kinetics of three alkaloids and their four metabolites from Simiao Pills in normal and type 2 diabetic rats. The diabetes model was established in rats by injection of streptozotocin, and the alkaloids in urine, feces, and bile of normal and diabetic rats were detected by LC-MS/MS to explore the effect of diabetes on alkaloid excretion of Simiao Pills. The results showed that 72 h after intragastric administration of the extract of Simiao Pills, feces were the main excretion route of alkaloids from Simiao Pills. The total excretion rates of magnoflorine and berberine in normal rats were 4.87% and 56.54%, which decreased to 2.35% and 35.53% in diabetic rats, which had statistical significance(P&lt;0.05). The total excretion rates of phellodendrine, magnoflorine, and berberine in the urine of diabetic rats decreased significantly, which were 53.57%, 60.84%, and 52.78% of those in normal rats, respectively. After 12 h of intragastric administration, the excretion rate of berberine in the bile of diabetic rats increased significantly, which was 253.33% of that of normal rats. In the condition of diabetes, the excretion rate of berberine metabolite, thalifendine significantly decreased in urine and feces, but significantly increased in bile. The total excretion rates of jateorrhizine and palmatine in the urine increased significantly, and t&#95;(1/2) and K&#95;e changed significantly. The results showed that diabetes affected the in vivo process of alkaloids from Simiao Pills, reducing their excretion in the form of prototype drug, affecting the biotransformation of berberine, and ultimately increasing the exposure of alkaloids in vivo, which would be conducive to the hypoglycemic effect of alkaloids. This study provides references for the clinical application and drug development of Simiao Pills in diabetes.

Background: Evodia Rutaecarpa-processed Coptidis Rhizoma (ECR) is a traditional Chinese medicine for the treatment of ulcerative colitis (UC) in China. However, the mechanisms underlying the ECR processing are not elucidated., Purpose: Coptidis Rhizoma (CR) regulates the gut microbiota in the treatment of gastrointestinal diseases. This study explored the mechanism of action of ECR before and after processing in UC in view of the regulation of gut microecology., Study Design: A preclinical experimental investigation was performed using a mouse model of UC to examine the regulatory effect of ECR and its mechanisms through gut microbiota analysis and metabolomic assays., Methods: Mice received 4% dextran sulfate sodium to establish a UC model and treated with ECR and CR. Colonic histopathology and inflammatory changes were observed. Gut microbiota was analyzed using 16 s rRNA sequencing. Transplants of Lactobacillus reuteri were used to explore the correlation between ECR processing and the gut microbiota. The expression of mucin-2, Lgr5, and PCNA in colonic epithelial cells was measured using immunofluorescence. Wnt3a and β-catenin levels were detected by western blotting. The metabolites in the colon tissue were analyzed using a targeted energy metabolomic assay. The effect of energy metabolite α-ketoglutarate (α-KG) on L. reuteri growth and UC were verified in mice., Results: ECR improved the effects on UC in mice compared to CR, including alleviating colonic injury and inflammation, and modulating gut microbiota by increasing L. reuteri level. L. reuteri dose-dependently alleviated colonic injury, increased mucin-2 level, and promoted colonic epithelial regeneration by increasing Lgr5 and PCNA expression. This was consistent with the results before and after ECR processing. L. reuteri promoted epithelial regeneration by upregulating Wnt/β-catenin pathway. Moreover, ECR increased metabolites levels (especially α-KG) to promote energy metabolism in the colon tissue compared to CR. α-KG treatment increased L. reuteri level and alleviated mucosal damage in UC mice. It promoted L. reuteri growth by increasing the energy metabolic status by enhancing α-KG dehydrogenase activity., Conclusion: ECR processing improves the therapeutic effects of UC via the α-KG-L. reuteri-epithelial regeneration axis., Competing Interests: Declaration of Competing Interest The Authors have no relevant interests to disclose. The authors have no conflicts of interest to declare that are relevant to the content of this article., (Copyright © 2023. Published by Elsevier GmbH.)

The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy., (© 2023. The Author(s).)

Spinosyn A (SPA), derived from a soil microorganism, Saccharopolyspora spinosa , and its derivative, LM2I, has potential inhibitory effects on a variety of cancer cells. However, the effects of SPA and LM2I in inhibiting the growth of human colorectal cancer cells and the molecular mechanisms underlying these effects are not fully understood. Cell viability was tested by using a 3-(4,5-dimethylthiazol-2-yl-)-2,5-diphenyltetrazolium bromide (MTT) assay and a colony formation assay. On the basis of the IC 50 values of SPA and LM2I in seven colorectal cancer (CRC) cell lines, sensitive (HT29 and SW480) and insensitive (SW620 and RKO) cell lines were screened. The GSE2509 and GSE10843 data sets were used to identify 69 differentially expressed genes (DEGs) between sensitive and insensitive cell lines. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interactions (PPI) were performed to elucidate the molecular mechanisms of the DEGs. The hub gene of the DEGs was detected by Western blot analysis and verified using the CRISPR/Cas9 system. Our data indicate that SPA and its derivative LM2I have significant antiproliferative activity in seven colorectal cancer cell lines and colorectal xenograft tumors. On the basis of bioinformatics analysis, it was demonstrated that epidermal growth factor receptor (EGFR) was the hub gene of the DEGs and was associated with the inhibitory effects of SPA and LM2I in CRC cell lines. The study also revealed that SPA and LM2I inhibited the EGFR pathway in vitro and in vivo.

Autophagy is critical to acrosome biogenesis and mitochondrial quality control, but the underlying mechanisms remain unclear. The ubiquitin ligase Nrdp1/RNF41 promotes ubiquitination of the mitophagy-associated Parkin and interacts with the pro-autophagic protein SIP/CacyBP. Here, we report that global deletion of Nrdp1 leads to formation of the round-headed sperm and male infertility by disrupting autophagy. Quantitative proteome analyses demonstrated that the expression of many proteins associated with mitochondria, lysosomes, and acrosomes was dysregulated in either spermatids or sperm of the Nrdp1-deficient mice. Deletion of Nrdp1 increased the levels of Parkin but decreased the levels of SIP, the mitochondrial fission protein Drp1 and the mitochondrial protein Tim23 in sperm, accompanied by the inhibition of autophagy, the impairment of acrosome biogenesis and the disruption of mitochondrial arrangement in sperm. Thus, our results uncover an essential role of Nrdp1 in spermiogenesis and male fertility by promoting autophagy, providing important clues to cope with the related male reproductive diseases.

Purpose: This study aimed to compare the efficacy of a special kind of intrauterine balloon (IUB) and that of an intrauterine contraception device (IUD) for patients with intrauterine adhesions (IUAs) after transcervical resection of adhesion (TCRA)., Methods: In this retrospective cohort study, after TCRA, 31 patients received a special IUB, and 38 patients received an IUD. The Fisher exact test, logistic regression method, Kaplan-Meier method and Cox proportional hazards regression model were used for statistical analysis. A two-sided value of P < 0.05 was considered statistically significant., Results: The readhesion rate significantly differed between the IUB group and IUD group, at 15.39% and 54.06%, respectively (P = 0.002). For recurrent moderate IUA, patients in the IUB group had lower scores than patients in the IUD group (P = 0.035). There was a significant difference in the intrauterine pregnancy rate of IUA patients in the IUB group and IUD group after treatment, with rates of 55.56% and 14.29%, respectively (P = 0.015)., Conclusion: Patients in the special IUB group had better outcomes than those in the IUD group, which has a certain guiding significance for clinical work., (© 2023. The Author(s).)

Ketamine is a new, fast, and effective antidepression treatment method; however, the possible dissociation effects, sensory changes, abuse risk, and the inability to accurately identify whether patients have a significant response to ketamine limit its clinical use. Further exploration of the antidepressant mechanisms of ketamine will contribute to its safe and practical application. Metabolites, the products of upstream gene expression and protein regulatory networks, play an essential role in various physiological and pathophysiological processes. In traditional metabonomics it is difficult to achieve the spatial localization of metabolites, which limits the further analysis of brain metabonomics by researchers. Here, we used a metabolic network mapping method called ambient air flow-assisted desorption electrospray ionization (AFADESI)-mass spectrometry imaging (MSI). We found the main changes in glycerophospholipid metabolism around the brain and sphingolipid metabolism changed mainly in the globus pallidus, which showed the most significant metabolite change after esketamine injection. The spatial distribution of metabolic changes was evaluated in the whole brain, and the potential mechanism of esketamine's antidepressant effect was explored in this research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Li, Lin, Wang, Luo, Wu, Zhou and Ning.)

To further understand the effect of volatile organic compounds (VOCs) on ozone (O 3 ) formation in seasons when ozone (O 3 ) pollution occurs frequently, the variation in VOCs, chemical composition characteristics, and ozone formation potential (OFP) were studied, using high-resolution online monitoring data obtained in an urban site of Beijing in the summer of 2019. The results showed that the averaged total mixing ratio of VOCs was (25.12±10.11)×10 -9 , with alkanes as the most abundant group (40.41%), followed by oxygenated volatile organic compounds (OVOCs) (25.28%) and alkenes/alkynes (12.90%). The diurnal variation in VOCs concentration showed a bimodal pattern with the morning peak appearing from 06:00 to 08:00, when the proportion of alkenes/alkynes increased significantly,indicating that the vehicle exhaust contributed more to VOCs. The VOCs concentration decreased in the afternoon when the proportion of OVOCs showed an upward trend, and the photochemical reaction and meteorological factors had great influences on VOCs concentration and composition.The OFP in urban Beijing in summer was 154.64 μg·m -3 ; aromatics, OVOCs, and alkenes/alkynes played dominant roles in OFP; and hexanal, ethylene, and m/p -xylene were the key species. The results suggested the need for the control of vehicle and solvent use and restaurants emissions to reduce the high level of O 3 in urban Beijing in summer. The diurnal variations in ethane/acetylene (E/E) and m/p -xylene/ethylbenzene (X/E) showed that the photochemical-aging of the air masses was obvious, which was jointly affected by photochemical reactions and regional transport. The back-trajectory results indicated a high contribution of southeastern and southwestern air masses to atmospheric alkanes and OVOCs concentration; moreover, aromatics and alkenes were mainly from local sources.

To analyze the efficacy and influencing factors of Mifepristone combined with estrogen-progesterone sequential therapy (Femoston) in the treatment of incomplete abortion. This retrospective cohort study included 93 patients with incomplete abortion. All patients took 50 mg of Mifepristone 2 times a day for 5 days and then took Femoston once a day (starting with estradiol tablets/2 mg) for 28 days. Without any indication of intrauterine residue by ultrasonic examination was judged to be effective. According to statistical analysis, this study calculated the effective rate and analyzed its influencing factors. A 2-sided value of P < .05 was considered statistically significant. The total response rate of the treatment regimen was 86.67%. body mass index was a significant influencing factor for treatment outcome (OR 0.818, 95% confidence interval 0.668-0.991, P = .041). For patients with incomplete abortion, Mifepristone combined with estrogen-progesterone sequential therapy has a remarkable therapeutic effect. Patients with a lower body mass index may respond much more significantly to this treatment regimen., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Human papillomavirus (HPV) is the main cause of cervical cancer. The aim of the present study was to investigate HPV DNA detection and genotyping on paired genital and urine samples and to evaluate if urine samples could be used to monitor HPV infection., Methods: Study subjects were recruited from one local hospital in Guangdong of China from September 1, 2011, to June 30, 2012. They were invited to participate if they have taken an HPV genotyping assay for clinical diagnosis of the genital-urinary disease or for a health check-up 3-5 days ago. DNA was extracted from paired genital and urine samples; genotyping was performed with the GenoArray assay., Results: A total of 250 patients were recruited, which included 203 females and 47 males. Our results showed that the overall agreement on HPV status between the paired samples was 77.1% (155/201, 95% CI: 0.713-0.829) for females, with a kappa value of 0.523 (95% CI: 0.469-0.632), while the agreement was extremely low in the paired male samples. As to individual genotyping, the greatest agreement was found for HPV16 type-specific identification in females (96.02%, 0.933-0.987), followed by the other 12 high oncogenic risk (HR-HPV) types, while the agreement for low-risk HPV detection is poor ( κ  < 0.6). Agreement between paired samples showed that HPV detection had a significantly greater concordance in the samples obtained in females than males ( p  = 0.002). Moreover, the agreement for low-risk HPV detection was significantly lower as compared to HR-HPV detection (48.1% vs. 62.3%, p  = 0.044)., Conclusion: Despite reduced sensitivity, HPV detection in urine closely represents the same trend that is seen with genital sampling. Urine appears to be an appropriate surrogate sample for HPV DNA detection in women with very limited access to healthcare, while the utility of urine for HPV DNA detection in males is less certain., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2023 Hui Yang et al.)

Background: Given the limitations of traditional pharmacology pedagogical method, diverse novel teaching methods have been widely explored. In this study, we performed a network meta-analysis (NMA) to evaluate the effects of different strategies in pharmacology education. Methods: Literature databases were searched from their inception to November 2022, and the studies were screened according to predefined inclusion and exclusion criteria to extract important information. Outcomes, including theoretical test scores, experimental test scores, subjective test scores, satisfaction scores, and the proportion of satisfaction, were analyzed using R software (version 3.6.1) and STATA (version 15). The NMA was conducted with a random-effects model under the Bayesian framework to calculate odds ratios (ORs) or mean differences (MDs) with associated 95% credible intervals (95% CIs). Surface under the cumulative ranking curve (SUCRA) probability values were calculated to rank the teaching methods examined. Results: A total of 150 studies involving 21,269 students were included. This NMA systematically evaluated 24 teaching strategies, such as problem-based learning (PBL), team-based learning (TBL), case-based learning (CBL) and flipped classrooms (FC), etc., The results of the NMA showed that, PBL combined with CBL was most likely to improve students' theoretical and subjective test scores (SUCRA = 75.49 and 98.19%, respectively), TBL was most likely to improve the experimental test score (SUCRA = 92.38%) and the satisfaction score (SUCRA = 88.37%), while FC had the highest probability of being the best option for improving the proportion of satisfaction (SUCRA = 84.45%). Conclusion: The current evidence indicates that TBL, PBL combined with CBL, and FC might be optimal strategies for pharmacology education since they have a more beneficial effect on students., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xiao, Ren, Chen, Liu, Luo, Li and Luo.)

Introduction: The genus Trissolcus includes a number of egg parasitoids that are known to contribute to the control of Halyomorpha halys . The number of progenies, particularly females, is important for the efficient mass rearing of species used in augmentative biological control programs. Cold storage is an important technique for extending the shelf life of natural enemies used in such programs. Methods: We assessed how fecundity, sex ratio, lifespan, and the number of hosts parasitized within 24 h were affected by host density for T. japonicus and T. cultratus when offered fresh H. halys eggs and how these parameters were affected if adult parasitoids were first placed in cold storage (11°C in the dark) for 19 weeks before being used for propagation. Results: The fecundity were 110.2 and 84.2 offspring emerged at 25°C, for parasitoids not placed in cold storage; among the offspring that emerged, 82.6% and 85.6% were female for T. japonicus and T. cultratus , respectively. If first placed in cold storage, T. japonicus and T. cultratus produced 35.1 and 24.6 offspring per female, respectively, although cold storage significantly extended the shelf life. The survival rates of parasitoids that were placed in cold storage were 90.3% and 81.3% for females, and 3.2% and 0.9% for males of T. japonicus and T. cultratus , respectively. The number of hosts parasitized within 24 h was not shown to be density dependent, but it was significantly lower after cold storage. Discussion: This information can be used to estimate the likely production for augmented rearing colonies for use in biological control programs., Competing Interests: GA was employed by The New Zealand Institute for Plant and Food Research Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Li, Chen, Avila, Ali, Tian, Luo, Zhang, Shi and Zhang.)

Ethnopharmacological Relevance: Xianglian pill (XLP), a traditional Chinese formula, is widely used as treatment for ulcerative colitis (UC) in China. However, the mechanism of its therapeutic effect is still unclear., Aim of the Study: Our previous studies showed a low oral bioavailability and a predominant distribution of major XLP ingredients in the gut. In the present study, we aimed to explore the mechanism of action of XLP on UC with respect to the regulation of gut microecology., Materials and Methods: UC model rats established using 5% dextran sulfate sodium were treated with XLP. After the treatment period, bodyweight, colon length, histopathology, and inflammatory changes were evaluated. Further, changes in gut microbiota structure were detected via 16S rRNA sequencing, and microbial metabolites in feces were analyzed via a metabolomic assay. Antibiotic intervention and fecal microbiota transplantation were also employed to explore the involvement of gut microbiota, while the level of regulatory T cells (Tregs) in mesenteric lymph nodes was determined via flow cytometry. Transcriptome sequencing was also performed to determine colonic gene changes., Results: XLP alleviated colonic injury, inflammation, and gut microbial dysbiosis in UC model rats and also changed microbial metabolite levels. Particularly, it significantly decreased succinate level in the tyrosine pathway. We also observed that fecal microbiota derived from XLP-treated rats conferred resilience to UC model rats. However, this therapeutic effect of XLP on UC was inhibited by succinate. Moreover, XLP increased the level of anti-inflammatory cellular Tregs via gut microbiota. However, this beneficial effect was counteracted by succinate supplementation. Further, XLP induced the differentiation of Treg possibly by the regulation of the PHD2/HIF-1α pathway via decreasing microbial succinate production., Conclusions: Our findings indicated that XLP exerts its therapeutic effects on UC mainly via the gut microbiota-succinate-Treg differentiation axis., Competing Interests: Declaration of competing interest The authors declared that they have no conflicts of interest to this work. We declare that we do not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The OlympiA trial demonstrated the benefits of adjuvant usage of olaparib for high-risk patients with human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) and germline BRCA (gBRCA) mutation. This provoked thoughts on the clinical criteria of gBRCA testing. This study aims to estimate the costs and benefits of gBRCA testing and adjuvant olaparib therapy for patients with triple-negative breast cancer (TNBC) and hormone-receptor (HR)-positive and HER2-negative BC in China and the United States of America (USA)., Methods: We used a Markov chain decision tree analytic model to compare three gBRCA screening policies in China and the USA: (1) no gBRCA testing; (2) selected gBRCA testing and (3) universal gBRCA testing for nonmetastatic TNBC and HR-positive HER2-negative BC patients. We modelled the benefit of systemic therapy and risk-reducing surgeries among patients identified with pathogenic or likely pathogenic variants (PVs) in BRCA1 and BRCA2., Results: Changing from the selected gBRCA testing to the universal gBRCA testing in TNBC patients is cost-effective, with the incremental cost-effectiveness ratios (ICERs) being 10991.1 and 56518.2 USD/QALY in China and the USA, respectively. Expanding universal gBRCA testing to HR-positive HER2-negative BC and TNBC patients has ICERs of 2023.3 and 16611.1 USD/QALY in China and the USA, respectively., Discussion: By performing gBRCA testing on all HER2-negative BC patients, adjuvant olaparib can be offered to high-risk patients with a PV in BRCA1 or BRCA2. These patients are also candidates for risk-reducing surgeries, an important aspect of their survivorship care, and these interventions can improve survival outcomes. With the willingness-to-pay thresholds being 31,500.0 and 100,000.0 USD per QALY gained in China and the USA, respectively, universal gBRCA testing is likely cost-effective for all HER2-negative BC patients. This simplified criterion of gBRCA testing for BC is recommended for adoption by current guidelines in China and the USA., (© 2022. The Author(s).)

The prevalence of sarcopenia and its clinical predictors and clinical impact vary among kidney transplant recipients (KTRs), in part because of different diagnostic criteria. This study aimed to assess the reported diagnosis criteria of sarcopenia and compare them in terms of prevalence, clinical predictors, and impact of sarcopenia. The Medline, Embase, and Cochrane Library were searched for the full-length reports published until 28 January 2022. The subgroup analysis, meta-regression, and sensitivity analysis were performed and heterogeneity was assessed using the I 2 . A total of 681 studies were retrieved, among which only 23 studies (including 2535 subjects, 59.7% men, mean age 49.8 years) were eventually included in the final analysis. The pooled prevalence in these included studies was 26% [95% confidence interval (95% CI): 20-34%, I 2  = 93.45%], including 22% (95% CI: 14-32%, I 2  = 88.76%) in men and 27% (95% CI: 14-41%, I 2  = 90.56%) in women (P = 0.554 between subgroups). The prevalence of sarcopenia diagnosed using low muscle mass was 34% (95% CI: 21-48%, I 2  = 95.28%), and the prevalence of using low muscle mass in combination with low muscle strength and/or low physical performance was 21% (95% CI: 15-28%, I 2  = 90.37%) (P = 0.08 between subgroups). In meta-regression analyses, the mean age (regression coefficient: 1.001, 95% CI: 0.991-1.011) and percentage male (regression coefficient: 0.846, 95% CI: 0.367-1.950) could not predict the effect size. Lower body mass index (odds ratio (OR): 0.57, 95% CI: 0.39-0.84, I 2  = 61.5%), female sex (OR: 0.31, 95% CI: 0.16-0.61, I 2  = 0.0%), and higher age (OR: 1.08, 95% CI: 1.05-1.10, I 2  = 10.1%) were significantly associated with a higher risk for sarcopenia in KTRs, but phase angle (OR: 0.81, 95% CI: 0.16-4.26, I 2  = 84.5%) was not associated with sarcopenia in KTRs. Sarcopenia was not associated with rejections (risk ratio (RR): 0.67, 95% CI: 0.23-1.92, I 2  = 12.1%), infections (RR: 1.03, 95% CI: 0.34-3.12, I 2  = 87.4%), delayed graft functions (RR: 0.81, 95% CI: 0.46-1.43, I 2  = 0.0%), and death (RR: 0.95, 95% CI: 0.32-2.82, I 2  = 0.0%) in KRTs. Sarcopenia was found to be very common in KRTs. However, we have not found that sarcopenia had a negative impact on clinical health after kidney transplantation. Large study cohorts and multicentre longitudinal studies in the future are urgently needed to explore the prevalence and prognosis of sarcopenia in kidney transplant patients., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: Type 2 diabetes mellitus (T2DM) is a metabolic disease. Simiao Wan (SMW) is a commonly used clinical drug for hyperuricemia treatment. SMW has been confirmed to improve insulin resistance and is expected to be a novel hypoglycemic agent. However, the hypoglycemic bioactive ingredients and mechanisms of action of SMW are unclear., Objective: To explore the hypoglycemic effects and reveal the mechanisms of SMW and bioactive ingredients (SMW-BI)., Study Design and Methods: The hypoglycemic effects of SMW and SMW-BI were verified in a mouse model of T2DM induced by streptozotocin (STZ) and a high-fat and high-sugar diet (HFSD). Network pharmacology was used to predict the mechanisms of SMW and SMW-BI. Histological analysis and real-time quantitative polymerase chain reaction (RT-qPCR) verified network pharmacology results. RT-qPCR results were further verified by immunofluorescence (IFC) and molecular docking. The correlation between proteins and biochemical indicators was analyzed by Spearman's correlation., Results: Chlorogenic acid, phellodendrine, magnoflorine, jateorhizine, palmatine, berberine, and atractydin were identified as SMW-BI. After 8 weeks of treatment, SMW and SMW-BI decreased the levels of fasting blood glucose (FBG), total cholesterol (TC), triacylglycerols (TG) and low-density lipoprotein cholesterol (LDL-C), increased the level of high-density lipoprotein cholesterol (HDL-C), alleviated weight loss, and increased serum insulin levels in T2DM mice. In addition, SMW and SMW-BI improved hepatocyte morphology in T2DM mice, decreased the number of adipocytes, and increased liver glycogen. Network pharmacological analysis indicated that SMW and SMW-BI may exert hypoglycemic by regulating insulin receptor substrate 1 (IRS1)/RAC-beta serine/threonine-protein kinase (AKT2)/forkhead box protein O1 (FOXO1)/glucose transporter type 2 (GLUT2) signaling. Moreover, correlation analysis showed that SMW and SMW-BI were associated with activation of IRS1, AKT2, and GLUT2, and inhibiting FOXO1. RT-qPCR revealed that SMW and SMW-BI could increase levels of IRS1, AKT2, and GLUT2 in the livers of T2DM mice and lower the level of FOXO1. Furthermore, immunofluorescence analysis showed that FOXO1 expression in the livers of T2DM mice decreased after oral administration of SMW and SMW-BI. Furthermore, molecular docking showed that SMW-BI could bind directly to IRS1 and AKT2., Conclusion: SMW and SMW-BI are potential hypoglycemic drugs that alleviate T2DM by regulating IRS1/AKT2/FOXO1 signaling. Our study provides a research idea for screening the bioactive ingredients in traditional Chinese medicine (TCM)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xia, Xu, Hu, Luo, He, Liu and Tan.)

Spinal cord injury (SCI) is a very serious clinical traumatic illness with a very high disability rate. It not only causes serious functional disorders below the injured segment, but also causes unimaginable economic burden to social development. Exosomes are nano-sized cellular communication carriers that exist stably in almost all organisms and cell types. Because of their capacity to transport proteins, lipids, and nucleic acids, they affect various physiological and pathological functions of recipient cells and parental cells. Autophagy is a process that relies on the lysosomal pathway to degrade cytoplasmic proteins and organelles and involves a variety of pathophysiological processes. Exosomes and autophagy play critical roles in cellular homeostasis following spinal cord injury. Presently, the coordination mechanism of exosomes and autophagy has attracted much attention in the early efficacy of spinal cord injury. In this review, we discussed the interaction of autophagy and exosomes from the perspective of molecular mechanisms, which might provide novel insights for the early therapeutic application of spinal cord injury., (© 2022. The Author(s).)

Objective: To investigate the related factors of radioiodine-refractory thyroid cancer (RAIR-DTC) and the increase of cumulative iodine treatment dose. Methods: The data of patients with papillary thyroid cancer who underwent surgery and iodine treatment for the first time in the Affiliated Cancer Hospital of Zhengzhou University from January 2015 to December 2017 were retrospectively analyzed. The related factors of RAIR-DTC and the increase of cumulative iodine treatment dose were explored. Results: A total of 650 patients were enrolled, including 217 males (33.4%) and 433 females (66.6%), aged 45 (34, 53) years. There were 123 patients (18.9%) over 55 years old, 171 patients (26.3%) with extranodal extension and 18 patients (2.8%) with distant metastasis. The median lymph node ratio was 0.22 (0.11, 0.33). Twenty patients (3.1%) had an accumulated iodine treatment dose>400 mCi and 19 patients (2.9%) had RAIR-DTC. Multivariate logistic regression analysis showed that extranodal extension ( OR =19.833, 95% CI : 6.057-73.325, P <0.001) was related factors for the increase of cumulative iodine treatment dose. Age>55 years old ( OR =3.322, 95% CI : 1.136-9.466, P =0.024), distant metastasis ( OR =10.059, 95% CI : 2.508-38.888, P <0.001), extranodal extension ( OR =5.278, 95% CI : 1.707-19.813, P =0.006) and lymph node ratio ( OR =34.724, 95% CI : 2.749-384.575, P =0.004) were related factors for RAIR-DTC. Conclusions: Extranodal extension and lymph node ratio are related factors for RAIR-DTC. In clinical practice, more attention should be paid to the influence of different lymph node metastasis characteristics on the occurrence of RAIR-DTC and the cumulative therapeutic dose of iodine.

DDX41 is an intracellular DNA sensor that evokes type I interferon (IFN-I) production via the adaptor stimulator of interferon gene (STING), triggering innate immune responses against viral infection. However, the regulatory mechanism of the DDX41-STING pathway in teleost fish remains unclear. The mandarin fish ( Siniperca chuatsi ) is a cultured freshwater fish species that is popular in China because of its high market value. With the development of a high-density cultural mode in mandarin fish, viral diseases have increased and seriously restricted the development of aquaculture, such as ranavirus and rhabdovirus. Herein, the role of mandarin fish DDX41 ( sc DDX41) and its DEAD and HELIC domains in the antiviral innate immune response were investigated. The level of sc DDX41 expression was up-regulated following treatment with poly(dA:dT) or Mandarin fish ranavirus (MRV), suggesting that sc DDX41 might be involved in fish innate immunity. The overexpression of sc DDX41 significantly increased the expression levels of IFN-I, ISGs, and pro-inflammatory cytokine genes. Co-immunoprecipitation and pull-down assays showed that the DEAD domain of sc DDX41 recognized the IFN stimulatory DNA and interacted with STING to activate IFN-I signaling pathway. Interestingly, the HELIC domain of sc DDX41 could directly interact with the N-terminal of STING to induce the expression levels of IFN-I and ISGs genes. Furthermore, the sc DDX41 could enhance the sc STING-induced IFN-I immune response and significantly inhibit MRV replication. Our work would be beneficial to understand the roles of teleost fish DDX41 in the antiviral innate immune response.

The enhanced biodegradation of oil-contaminated soil by fixing microorganisms with corn cob biochar was investigated. It was found that the components of oil in the test soil were mainly straight-chain alkanes and branched alkanes. When using corn cob biochar as a carrier to immobilize microorganisms, the best particle size of corn cob biochar as an immobilization carrier was 0.08 mm, and the best immobilization time was 18 h. SEM analysis confirmed that the microorganisms were immobilized on the corn cob biochar. Immobilized microorganisms exhibited high biodegradability under stress to high concentrations of petroleum pollutants, heavy metals, and organic pollutants. Infrared spectroscopy analysis showed that oxygen-containing groups such as hydroxyl, carboxyl, and methoxy on the surface of biochar were involved in the complexation of heavy metals. The mechanism of immobilization promoted microbial degradation of oil contamination was explained by gas chromatography mass. First, alkanes and aromatics were adsorbed by corn cob biochar and passed to immobilized microorganisms to promote their degradation. Their bioavailability increased, especially for aromatics. Second, biochar provided a more suitable environment for microorganisms to degrade. Third, the conversion of ketones to acids was accelerated during the biodegradation of alkanes, and the biodegradation of alkanes was accelerated by immobilization. The biodegradable efficiency of oil by immobilized microorganisms in soil was 70.10% within 60 days, 28.80% higher than that of free microorganisms. The degradation of immobilized microorganisms was highly correlated with the activities of catalase, urease, and polyphenol oxidase., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)