Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery.Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024.Morphological evaluation,immunohistochemical staining,and next generation sequencing(NGS)targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions.Results All three implanted lesions exhibited morphological similarity to their primary counterparts,but displayed enriched mutational profiles.Case 1:a 13-year-old female.The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma,while the implanted lesion was follicular carcinoma.Both lesions harbored MEN1 mutations,with an additional PTPRT mutation detected in the implanted lesion.Case 2:a 45-year-old male.The primary lesion was bilateral nodular goiter,and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus.No mutations were identified in the primary lesion,whereas the implanted lesion exhibited MEN1,GLIS3,EZH1,and KMT2C mutations.Case 3:a 42-year-old female.The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter.A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively.The primary lesion harbored TERT,GLIS3,and SPOP mutations,while the implanted lesion showed TERT,GLIS3,EIF1AX,and KMT2C mutations.Conclusions Endoscopic thyroid surgery is widely applied in clinical practice,however,implantation dissemination of thyroid lesions along surgical pathways may occur,encompassing both benign and malignant entities.Implanted lesions exhibit pathological similarities to their primary counterparts,but demonstrate mutational enrichment.

BACKGROUND:Accurate early diagnosis and timely reperfusion therapy are important prerequisites for saving the lives and improving the prognosis of patients with acute myocardial infarction.Therefore,it is important to find ideal biomarkers for early diagnosis of acute myocardial infarction.OBJECTIVE:To analyze key genes associated with neutrophils by acute myocardial infarction through bioinformatics and machine learning to explore new biomarkers.METHODS:Differentially expressed genes were identified based on the Gene Expression Omnibus(GEO)database and Limma R package.Deconvolution algorithm was used to explore the immune cells infiltration level.Then,acute myocardial infarction and neutrophils-related biomarkers were screened by weighted gene co-expression network analysis(WGCNA),protein-protein interaction(PPI)networks,machine learning,and functional enrichment analysis.Receiver operating characteristic curve analysis was conducted to assess the diagnostic efficacy of biomarkers for acute myocardial infarction.Targeted drugs for biomarkers were screened through the STITCH and Herb database.Finally,the hospitalized patients who were first diagnosed with acute myocardial infarction in the Department of Cardiology of Affiliated Hospital of Guizhou Medical University from March to June 2023 were used as the experimental group,and the hospitalized patients who had no ischemic changes on electrocardiograms and no stenosis on coronary angiograms during the same period were used as the control group.Peripheral blood of the patients in the two groups was collected.The relative expressions of the genes were verified in the human peripheral blood samples by RT-qPCR.RESULTS AND CONCLUSION:(1)A total of 2 349 differentially expressed genes were obtained,and immune infiltration analysis revealed differences in immune cell scores such as B cells memory,NK cells resting,and Neutrophils between the disease and normal groups.(2)Using WGCNA,two gene modules,ME green and ME turquoise,were found to exhibit the highest correlation with neutrophil fine with acute myocardial infarction.(3)Twenty-four differential module genes were obtained after intersecting with differentially expressed genes.Functional enrichment analysis revealed that they were associated with a variety of processes such as innate immune response and defense response to bacteria.KEGG results showed that they were mainly associated with the tumor necrosis factor signaling pathway.(4)The genes mined by the machine learning algorithm took the intersection to obtain three genes,namely,S100A12,PTCH1,and LOC400499,all of which were greater than 0.7 by the area under the receiver operating characteristic curve in both the GSE48060 and GSE66360 datasets.They were considered as potential biomarkers.(5)Based on the STITCH and Herb databases,11 target drugs were found for S100A12 and a total of 6 target drugs were found for PTCH1.(6)RT-qPCR results showed that S100A12,PTCH1,and LOC400499 were significantly differentially expressed in acute myocardial infarction patients compared with controls(P＜0.05).(7)S100A12,PTCH1,and LOC400499 may be potential diagnostic biomarkers for acute myocardial infarction,but their specificity in relation to acute myocardial infarction needs to be further investigated,in which S100A12 may be a potential target for regulating acute myocardial infarction.

Objective To investigate the pathological and molecular characteristics of subcutaneous implanted thyroid lesions after endoscopic thyroid surgery. Methods A retrospective analysis was conducted on three postoperative implantation cases diagnosed in the Department of Pathology of our hospital from 2017 to 2024. Morphological evaluation, immunohistochemical staining, and next generation sequencing (NGS) targeting 66 cancer-related genes and 177 fusion loci were performed to compare features between primary and implanted lesions. Results All three implanted lesions exhibited morphological similarity to their primary counterparts, but displayed enriched mutational profiles. Case 1: a 13-year-old female. The primary lesion was an atypical follicular adenoma progressing to follicular carcinoma, while the implanted lesion was follicular carcinoma. Both lesions harbored MEN1 mutations, with an additional PTPRT mutation detected in the implanted lesion. Case 2: a 45-year-old male. The primary lesion was bilateral nodular goiter, and the implanted lesion showed follicular epithelial hyperplasia with a 0.3 cm papillary carcinoma focus. No mutations were identified in the primary lesion, whereas the implanted lesion exhibited MEN1, GLIS3, EZH1, and KMT2C mutations. Case 3: a 42-year-old female. The primary lesion included a left thyroid adenoma with cystic degeneration and right nodular goiter. A nodular goiter-like implanted lesion was detected in the right breast 5 years postoperatively. The primary lesion harbored TERT, GLIS3, and SPOP mutations, while the implanted lesion showed TERT, GLIS3, EIF1AX, and KMT2C mutations. Conclusions Endoscopic thyroid surgery is widely applied in clinical practice, however, implantation dissemination of thyroid lesions along surgical pathways may occur, encompassing both benign and malignant entities. Implanted lesions exhibit pathological similarities to their primary counterparts, but demonstrate mutational enrichment.

Several types of arthritis share the common feature that the generation of inflammatory mediators leads to joint cartilage degradation. However, the shared mechanism is largely unknown. H2BK120ub1 was reportedly involved in various inflammatory diseases but its role in the shared mechanism in inflammatory joint conditions remains elusive. The present study demonstrated that levels of cartilage degradation, H2BK120ub1, and its regulator WW domain-containing adapter protein with coiled-coil (WAC) were increased in cartilage in human rheumatoid arthritis (RA) and osteoarthritis (OA) patients as well as in experimental RA and OA mice. By regulating H2BK120ub1 and H3K27me3, WAC regulated the secretion of inflammatory and cartilage-degrading factors. WAC influenced the level of H3K27me3 by regulating nuclear entry of the H3K27 demethylase KDM6B, and acted as a key factor of the crosstalk between H2BK120ub1 and H3K27me3. The cartilage-specific knockout of WAC demonstrated the ability to alleviate cartilage degradation in collagen-induced arthritis (CIA) and collagenase-induced osteoarthritis (CIOA) mice. Through molecular docking and dynamic simulation, doxercalciferol was found to inhibit WAC and the development of cartilage degradation in the CIA and CIOA models. Our study demonstrated that WAC is a key factor of cartilage degradation in arthritis, and targeting WAC by doxercalciferol could be a viable therapeutic strategy for treating cartilage destruction in several types of arthritis.

OBJECTIVE: To observe the efficacy and safety of moxibustion in treating patients with central obesity of phlegm-dampness constitution. METHODS: A total of 66 patients with central obesity of phlegm-dampness constitution were randomly assigned to a moxibustion group (n=33, 3 cases dropped out) and a sham moxibustion group (n=33, 4 cases dropped out). The moxibustion group received mild moxibustion combined with lifestyle intervention; the moxibustion was applied at Shenque (CV8) and bilateral Zusanli (ST36), 30 min per session, maintaining a local skin temperature of (43±1) ℃. The sham moxibustion group received simulated moxibustion combined with lifestyle intervention; the simulated moxibustion was applied at the same acupoints, with the same session length, but with a maintained skin temperature of (37±1) ℃. Both groups were treated once every other day, three times per week for 8 consecutive weeks. Obesity-related physical indicators (waist circumference, hip circumference, body weight, body fat percentage, body mass index [BMI]), constitution evaluation indicators (phlegm-dampness constitution conversion score, symptom score), the impact of weight on quality of life-lite (IWQOL-Lite), the hospital anxiety and depression scale (HADS), and the incidence of adverse events were measured before and after treatment, and after 4 weeks of follow-up. RESULTS: Compared with before treatment, both groups showed significant reductions in waist circumference, hip circumference, body weight, body fat percentage, BMI, phlegm-dampness constitution conversion score and symptom score, IWQOL-Lite, and both anxiety and depression subscale scores of HADS after treatment and at follow-up (P<0.001). These improvements were significantly greater in the moxibustion group than those in the sham moxibustion group (P<0.001, P<0.01, P<0.05). One patient in the moxibustion group experienced a mild burn that resolved with routine care; the incidence of adverse reactions was 3.0% (1/33) in the moxibustion group and 0% (0/33) in the sham moxibustion group, with no statistically significant difference (P>0.05). CONCLUSION On the basis of lifestyle intervention, moxibustion effectively improves obesity-related physical indicators, enhances quality of life, alleviates anxiety and depression, and improves the phlegm-dampness constitution in patients with central obesity. These benefits persist for at least 4 weeks after treatment.
Humans ; Moxibustion ; Male ; Female ; Middle Aged ; Adult ; Obesity, Abdominal/psychology* ; Acupuncture Points ; Treatment Outcome ; Aged ; Quality of Life ; Young Adult ; Body Mass Index

BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

The production of high-quality oocytes requires precisely orchestrated intercellular communication. Extracellular vesicles (EVs) are cell-derived nanoparticles that play a vital role in the transfer of bioactive molecules, which has gained much attention in the field of diagnosis and treatment. Over the past ten years, the participation of EVs in the reproductive processes of oocytes has been broadly studied and has shown great potential for elucidating the intricacies of female reproductive health. This review provides an extensive discussion of the influence of EVs on oocytes, emphasizing their involvement in normal physiology and altered cargo under pathological conditions. In addition, the positive impact of therapeutic EVs on oocyte quality and their role in alleviating ovarian pathological conditions are summarized.
Humans ; Extracellular Vesicles/physiology* ; Oocytes/cytology* ; Female ; Animals ; Cell Communication/physiology*

BACKGROUND:Accurate early diagnosis and timely reperfusion therapy are important prerequisites for saving the lives and improving the prognosis of patients with acute myocardial infarction.Therefore,it is important to find ideal biomarkers for early diagnosis of acute myocardial infarction.OBJECTIVE:To analyze key genes associated with neutrophils by acute myocardial infarction through bioinformatics and machine learning to explore new biomarkers.METHODS:Differentially expressed genes were identified based on the Gene Expression Omnibus(GEO)database and Limma R package.Deconvolution algorithm was used to explore the immune cells infiltration level.Then,acute myocardial infarction and neutrophils-related biomarkers were screened by weighted gene co-expression network analysis(WGCNA),protein-protein interaction(PPI)networks,machine learning,and functional enrichment analysis.Receiver operating characteristic curve analysis was conducted to assess the diagnostic efficacy of biomarkers for acute myocardial infarction.Targeted drugs for biomarkers were screened through the STITCH and Herb database.Finally,the hospitalized patients who were first diagnosed with acute myocardial infarction in the Department of Cardiology of Affiliated Hospital of Guizhou Medical University from March to June 2023 were used as the experimental group,and the hospitalized patients who had no ischemic changes on electrocardiograms and no stenosis on coronary angiograms during the same period were used as the control group.Peripheral blood of the patients in the two groups was collected.The relative expressions of the genes were verified in the human peripheral blood samples by RT-qPCR.RESULTS AND CONCLUSION:(1)A total of 2 349 differentially expressed genes were obtained,and immune infiltration analysis revealed differences in immune cell scores such as B cells memory,NK cells resting,and Neutrophils between the disease and normal groups.(2)Using WGCNA,two gene modules,ME green and ME turquoise,were found to exhibit the highest correlation with neutrophil fine with acute myocardial infarction.(3)Twenty-four differential module genes were obtained after intersecting with differentially expressed genes.Functional enrichment analysis revealed that they were associated with a variety of processes such as innate immune response and defense response to bacteria.KEGG results showed that they were mainly associated with the tumor necrosis factor signaling pathway.(4)The genes mined by the machine learning algorithm took the intersection to obtain three genes,namely,S100A12,PTCH1,and LOC400499,all of which were greater than 0.7 by the area under the receiver operating characteristic curve in both the GSE48060 and GSE66360 datasets.They were considered as potential biomarkers.(5)Based on the STITCH and Herb databases,11 target drugs were found for S100A12 and a total of 6 target drugs were found for PTCH1.(6)RT-qPCR results showed that S100A12,PTCH1,and LOC400499 were significantly differentially expressed in acute myocardial infarction patients compared with controls(P＜0.05).(7)S100A12,PTCH1,and LOC400499 may be potential diagnostic biomarkers for acute myocardial infarction,but their specificity in relation to acute myocardial infarction needs to be further investigated,in which S100A12 may be a potential target for regulating acute myocardial infarction.

Isopentenyl flavonoids are a class of characteristic components in Sophora flavescens Ait. (S. flavescens). They have biological activities such as anti-tumor, anti-bacteria, anti-inflammol/ Lation and anti-oxidation. In this paper, the structural types, toxicology and pharmacological effects of isopentenyl flavonoids from S. flavescens were briefly reviewed. Furthermore, the worth of further study on pharmacokinetics, pharmacodynamics, toxicology, action targets, molecular mechanisms and structure-function relationships of isopentenyl flavonoids were proposed. The deep exploration on functional characterastics of isopentenyl flavonoids of S. flavescens and their application on development of innovative drugs are of great significance to further improve the added value of isopentenyl flavonoids and expand their application fields.

Objective:To analyze the changes in biological characteristics including infectivity, growth and pathogenicity of Chlamydia muridarum ( Cm) after serial passage in vitro in special conditions in order to provide reference for screening attenuated live vaccines and virulence-related genes. Methods:Wild-type Cm strain (G0) was cultured for several passages using conventional cell culture method under alternate unassisted and assisted culture conditions. Then, the 28th generation (G28) of Cm was selected and compared with the parental G0 strain in terms of centrifugation dependence, attaching ability, intracellular growth curve, plaque size and fallopian tube lesions after genital tract infection in a mouse model. Results:Compared with the parental G0 strain, the G28 strain showed significantly decreased dependence on centrifugation during cell infection ( P<0.05) and increased attachment capacity to cells ( P<0.05). No significant differences were observed in the growth curves 32 h after cell infection or in the plaque sizes between the parental G0 and G28 strains. In the in vivo virulence test, fallopian tube lesions were observed in 87.5% of G0-infected mice and 37.5% of G28-infected mice ( P<0.05). Conclusions:Compared with the parental G0 strain, the G28 strain showed significantly enhanced in vitro infection ability, but decreased in vivo pathogenicity, which brought hope for further identification of virulence genes, isolation of attenuated strains with single genotype and development of live attenuated Chlamydia vaccines.