Objective To analyze the structural and phylogenetic characteristics of the mitochondrial genome from Bulinus globosus, so as to provide a theoretical basis for classification and identification of species within the Bulinus genus, and to provide insights into understanding of Bulinus-schistosomes interactions and the mechanisms of parasite transmission. Methods B. globosus samples were collected from the Ruya River basin in Zimbabwe. Mitochondrial DNA was extracted from B. globosus samples and the corresponding libraries were constructed for high-throughput sequencing on the Illumina NovaSeq 6000 platform. After raw sequencing data were subjected to quality control using the fastp software, genome assembly was performed using the A5-miseq and SPAdes tools, and genome annotation was conducted using the MITOS online server. Circular maps and sequence plots of the mitochondrial genome were generated using the CGView and OGDRAW software, and the protein conservation motifs and structures were analyzed using the TBtools software. Base composition and codon usage bias were analyzed and visualized using the software MEGA X and the ggplot2 package in the R software. In addition, a phylogenetic tree was created in the software MEGA X after sequence alignment with the software MAFFT 7, and visualized using the software iTOL. Results The mitochondrial genome of B. globosus was a 13 730 bp double-stranded circular molecule, containing 2 ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and 13 protein-coding genes, with a marked AT preference. The mitochondrial genome composition of B. globosus was similar to that of other species within the Bulinus genus. Phylogenetic analysis revealed that the complete mitochondrial genome sequence of B. globosus was clustered with B. truncatus, B. nasutus, and B. ugandae into the same evolutionary clade, and gene superfamily analysis showed that the metabolism-related proteins of B. globosus were highly conserved, notably the cytochrome c oxidase family, which showed a significant consistency. Conclusions This is the first whole mitochondrial genome sequencing to decode the compositional features of the mitochondrial genome of B. globosus from Zimbabwe and its evolutionary relationship within the Bulinus genus, which provides important insights for further understanding of the phylogeny and mitochondrial genome characteristics of the Bulinus genus.

Objective To investigate the feasibility of developing a grading diagnostic model for schistosomiasis-induced liver fibrosis based on B-mode ultrasonographic images and clinical laboratory indicators. Methods Ultrasound images and clinical laboratory testing data were captured from schistosomiasis patients admitted to the Second People’s Hospital of Duchang County, Jiangxi Province from 2018 to 2022. Patients with grade I schistosomiasis-induced liver fibrosis were enrolled in Group 1, and patients with grade II and III schistosomiasis-induced liver fibrosis were enrolled in Group 2. The machine learning binary classification tasks were created based on patients’radiomics and clinical laboratory data from 2018 to 2021 as the training set, and patients’radiomics and clinical laboratory data in 2022 as the validation set. The features of ultrasonographic images were labeled with the ITK-SNAP software, and the features of ultrasonographic images were extracted using the Python 3.7 package and PyRadiomics toolkit. The difference in the features of ultrasonographic images was compared between groups with t test or Mann-Whitney U test, and the key imaging features were selected with the least absolute shrinkage and selection operator (LASSO) regression algorithm. Four machine learning models were created using the Scikit-learn repository, including the support vector machine (SVM), random forest (RF), linear regression (LR) and extreme gradient boosting (XGBoost). The optimal machine learning model was screened with the receiver operating characteristic curve (ROC), and features with the greatest contributions to the differentiation features of ultrasound images in machine learning models with the SHapley Additive exPlanations (SHAP) method. Results The ultrasonographic imaging data and clinical laboratory testing data from 491 schistosomiasis patients from 2019 to 2022 were included in the study, and a total of 851 radiomics features and 54 clinical laboratory indicators were captured. Following statistical tests (t = −5.98 to 4.80, U = 6 550 to 20 994, all P values < 0.05) and screening of key features with LASSO regression, 44 features or indicators were included for the subsequent modeling. The areas under ROC curve (AUCs) were 0.763 and 0.611 for the training and validation sets of the SVM model based on clinical laboratory indicators, 0.951 and 0.892 for the training and validation sets of the SVM model based on radiomics, and 0.960 and 0.913 for the training and validation sets of the multimodal SVM model. The 10 greatest contributing features or indicators in machine learning models included 2 clinical laboratory indicators and 8 radiomics features. Conclusions The multimodal machine learning models created based on ultrasound-based radiomics and clinical laboratory indicators are feasible for intelligent identification of schistosomiasis-induced liver fibrosis, and are effective to improve the classification effect of one-class data models.

Objective:To analyze the categories, characteristics, and clinical symptoms of adverse reactions associated with thalidomide treatment for oral mucosal diseases, providing a reference for the safe use of this medication in patients.Methods:A cross-sectional study was conducted to retrospectively analyze the adverse reactions to thalidomide treatment in 44 patients with oral mucosal diseases who received treatment at the Third Affiliated Hospital of Air Force Medical University from January 2019 to December 2023. The correlation between the age and sex of patients experiencing adverse reactions, the timing of these reactions in relation to sex, the organs and their appendages affected by the adverse reactions, and the outcomes of these reactions were statistically analyzed.Results:The incidence of adverse reactions associated with thalidomide treatment at the hospital was 0.21% (44/21 329), with a higher prevalence among female patients. Multiple organs were affected in 50.00% (22/44) of the cases, though the reactions were relatively concentrated, primarily involving the skin and its appendages, the central and peripheral nervous systems, and the gastrointestinal system. The main manifestations included rash and dizziness.Conclusion:In the treatment of oral mucosal diseases with thalidomide, it is essential to monitor adverse drug reactions, particularly those affecting the nervous system. Special attention should be given to the potential teratogenicity of thalidomide in individuals of childbearing age. In addition, it is vital to consistently investigate strategies to ensure the safety of patients using medication at home.

This study was aimed at investigating the effect of lymphocyte activation gene-3(LAG3)on liver B lymphocyte subsets and their functions in WT and LAG3-KO mice infected with Echinococcus multilocularis(E.multilocularis).In a mouse model of E.multilocularis infection,the expression and localization of CD19 and α-SMA in liver were detected by immu nohistochemistry.CD80,CD86 and MHC-Ⅱ molecules expressed on B cells and their subsets in mice liver were detected by flow cytometry.After 12 weeks of infection,the area and percentage of CD19 in LAG3-KO group was slightly higher than that in WT group,but the difference was not statistically(t=-1.241、-1.237,P＞0.05).The area and percentage of a-SMA in LAG3-KO group was higher than that in WT group(t=-3.224、-3.227,P＜0.05).The proportion of CD80 and MHC-Ⅱ molecules expressed on liver B cells in LAG3-KO group was up-regulated(t=-2.379,-3.321,P＜0.05).The percentage of liver B2 cells in LAG3-KO group was higher than that in WT group(t=-2.695,P＜0.05).The expression of CD80 on Blb cells in LAG3-KO group was significantly up-regulated(t=-5.315,P＜0.001).The proportion of CD80 of B2 cells in LAG3-KO group was lower than that in WT group(t=2.806,P＜0.05).The expression of MHC-Ⅱ molecule in B2 cells in LAG3-KO group was up-regulated(t=-4.227,P＜0.01).It is suggested that LAG3 molecules affected the B cell subsets and func-tion of mouse liver in the middle stage of E.multilocularis infection,especially B2 lymphocytes.LAG3 molecule exerted an in-hibitory effect on the activation of B cells and the expression of MHC-class Ⅱ molecules,suggesting that it may be involved in B cell exhaustion caused by E.multilocularis.

OBJECTIVE: To observe the effects of Tiaoshen (regulating the spirit) acupuncture on cognitive function and sleep quality in patients with primary insomnia (PI). METHODS: Sixty patients with PI were randomly divided into an observation group (30 cases, 2 cases dropped off) and a control group (30 cases, 2 cases dropped off, 1 case was excluded). The patients in the observation group were treated with acupuncture at Baihui (GV 20), Shenting (GV 24), Sishencong (EX-HN 1), and bilateral Benshen (GB 13), Shenmen (HT 7), Neiguan (PC 6), Sanyinjiao (SP 6). The patients in the control group were treated with shallow needling at non-effective points. Each treatment was provided for 30 min, once every other day, 3 treatments per week for 4 weeks. The Montreal cognitive assessment (MoCA), digit span test (DST), trail making test (TMT)-A, Pittsburgh sleep quality index (PSQI), and fatigue scale-14 (FS-14) were used to assess cognitive function and sleep quality before and after treatment, as well as in follow-up of 4-week after treatment completion. Correlation analysis was conducted between the differences in PSQI scores and differences in MoCA scores before and after treatment in the observation group. RESULTS: Compared with before treatment, the total score, visuospatial and executive function score and delayed memory score of MoCA as well as DST backward score were increased (P<0.01), while TMT-A time, PSQI and FS-14 scores were significantly reduced (P<0.01) after treatment and in follow-up in the observation group. Compared with before treatment, the PSQI score in the control group was reduced (P<0.01, P<0.05). After treatment and in follow-up, the observation group had significantly higher total score, visuospatial and executive function score, delayed memory score of MoCA, and DST backward score compared to the control group (P<0.05, P<0.01). In the observation group, the TMT-A time was significantly shorter than that in the control group (P<0.05, P<0.01), and the PSQI and FS-14 scores were significantly lower than those in the control group (P<0.01). In the observation group, there was a negative correlation between the difference in PSQI scores (post-treatment minus pre-treatment) and the difference in MoCA scores (post-treatment minus pre-treatment) (r=-0.481, P<0.01). A similar negative correlation was found between the difference in PSQI scores (follow-up minus pre-treatment) and the difference in MoCA scores (follow-up minus pre-treatment) (r=-0.282, P<0.05). CONCLUSION Tiaoshen acupuncture could improve cognitive function, enhance sleep quality, and alleviate daytime fatigue in patients with PI. The improvement in cognitive function in patients with PI is correlated with the improvement in sleep quality.
Humans ; Pilot Projects ; Sleep Initiation and Maintenance Disorders/therapy* ; Acupuncture Therapy ; Cognition ; Fatigue

Humans ; Parkinson Disease/diagnosis* ; Machine Learning

OBJECTIVE: To investigate the effect of phorbol-12-myristate-13-ace-tate (TPA) on the proliferation and apoptosis of acute promyelocytic leukemia cell line NB4 and its molecular mechanism. METHODS: The effect of different concentrations of TPA on the proliferation of NB4 cells at different time points was detected by CCK-8 assay. The morphological changes of NB4 cells were observed by Wright-Giemsa staining. The cell cycle and apoptosis of NB4 cells after TPA treatment were detected by flow cytometry. The mRNA expressions of NB4 cells after TPA treatment were analyzed by high-throughput microarray analysis and real-time quantitative PCR. Western blot was used to detect the protein expression of CDKN1A, CDKN1B, CCND1, MYC, Bax, Bcl-2, c-Caspase 3, c-Caspase 9, PIK3R6, AKT and p-AKT. RESULTS: Compared with the control group, TPA could inhibit the proliferation of NB4 cells, induce the cells to become mature granulocyte-monocyte differentiation, and also induce cell G₁ phase arrest and apoptosis. Differentially expressed mRNAs were significantly enriched in PI3K/AKT pathway. TPA treatment could increase the mRNA levels of CCND1, CCNA1, and CDKN1A, while decrease the mRNA level of MYC. It could also up-regulate the protein levels of CDKN1A, CDKN1B, CCND1, Bax, c-Caspase 3, c-Caspase 9, and PIK3R6, while down-regulate MYC, Bcl-2, and p-AKT in NB4 cells. CONCLUSION TPA induces NB4 cell cycle arrest in G₁ phase and promotes its apoptosis by regulating PIK3/AKT signaling pathway.
Humans ; Leukemia, Promyelocytic, Acute ; Caspase 3/metabolism* ; Caspase 9/pharmacology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; bcl-2-Associated X Protein/metabolism* ; Cell Line, Tumor ; Cell Division ; Apoptosis ; RNA, Messenger ; Cell Proliferation

Carcinoma-associated fibroblasts (CAFs) are the main cellular components of the tumor microenvironment and promote cancer progression by modifying the extracellular matrix (ECM). The tumor-associated ECM is characterized by collagen crosslinking catalyzed by lysyl oxidase (LOX). Small extracellular vesicles (sEVs) mediate cell-cell communication. However, the interactions between sEVs and the ECM remain unclear. Here, we demonstrated that sEVs released from oral squamous cell carcinoma (OSCC)-derived CAFs induce collagen crosslinking, thereby promoting epithelial-mesenchymal transition (EMT). CAF sEVs preferably bound to the ECM rather than being taken up by fibroblasts and induced collagen crosslinking, and a LOX inhibitor or blocking antibody suppressed this effect. Active LOX (αLOX), but not the LOX precursor, was enriched in CAF sEVs and interacted with periostin, fibronectin, and bone morphogenetic protein-1 on the surface of sEVs. CAF sEV-associated integrin α2β1 mediated the binding of CAF sEVs to collagen I, and blocking integrin α2β1 inhibited collagen crosslinking by interfering with CAF sEV binding to collagen I. CAF sEV-induced collagen crosslinking promoted the EMT of OSCC through FAK/paxillin/YAP pathway. Taken together, these findings reveal a novel role of CAF sEVs in tumor ECM remodeling, suggesting a critical mechanism for CAF-induced EMT of cancer cells.
Humans ; Paxillin/metabolism* ; Protein-Lysine 6-Oxidase/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Epithelial-Mesenchymal Transition ; Integrin alpha2beta1/metabolism* ; Mouth Neoplasms/pathology* ; Collagen/metabolism* ; Fibroblasts ; Extracellular Vesicles/metabolism* ; Cell Line, Tumor ; Tumor Microenvironment

OBJECTIVES: To investigate the prevalence of polypharmacy and potentially inappropriate medication (PIM) in elderly patients with heart failure (HF) and their impact on readmission and mortality. METHODS: We conducted a study of 274 participants aged 60 years or older with HF. The prevalence of polypharmacy (defined as the use of five or more medications) was calculated, and the 2019 American Geriatrics Society Beers criteria were applied to access PIMs. Medications and PIMs were characterized at admission and discharge, and changes in prescriptions during hospitalization were compared. The impact of polypharmacy and PIM on readmission and mortality were investigated. RESULTS: The median age of this study population was 68 years old. The median number of prescribed drugs was 7 at admission and 10 at discharge. At discharge, 99.27% of all patients were taking five or more drugs. The incidence of composite endpoint and cardiovascular readmission increased with the number of polypharmacy within 6 months. The use of guideline-directed medical therapy reduced the incidence of composite endpoint events and cardiovascular readmission, while the use of non-cardiovascular medications increased the composite endpoint events. The frequency of PIMs was 93.79% at discharge. The incidence of composite endpoint events increased with the number of PIMs. "PIMs in older adults with caution" increased cardiovascular readmission and "PIMs based on kidney function" increased cardiovascular mortality. Several comorbidities were associated with cardiovascular mortality or non-cardiovascular readmission. CONCLUSIONS Polypharmacy and PIM were highly prevalent in elderly patients with HF, and their use was associated with an increased risk of composite endpoint events, readmission and mortality. Non-cardiovascular medications, "PIMs in older adults with caution", "PIMs based on kidney function" and several comorbidities were important factors associated with hospital readmission and mortality. Our findings highlight the importance of medication optimization in the management of HF in elderly patients.

OBJECTIVE: To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome. METHODS: In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded. RESULTS: From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05). CONCLUSION Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).
Humans ; Paroxetine/adverse effects* ; Spleen ; Anxiety ; Syndrome ; Medicine, Chinese Traditional ; Treatment Outcome ; Double-Blind Method