A bibliometric analysis of follicular thyroid carcinoma: Current situation, hot spots, and global trends.

BACKGROUND: Follicular thyroid carcinoma (FTC), the second most prevalent thyroid cancer after papillary thyroid cancer (PTC), tends to metastasize distantly, leading to poorer outcomes. Despite substantial research, a holistic bibliometric analysis of FTC literature is lacking. This study aims to fill this gap by employing bibliometric methods to track FTC research evolution. METHODS: English FTC publications were systematically gathered from the Web of Science. Bibliometric analysis, using R, VOSviewer, CiteSpace, and Excel, synthesized data and explored global research trends and topics. RESULTS: From 2000 to 2023, 9086 authors from 1953 institutions across 75 countries contributed to 1776 papers in 491 academic journals on FTC. The last two decades have witnessed a steady increase in publications related to FTC, with the United States leading in terms of publication volume. The United States dominated both in publications and citations, with the National Cancer Institute and Sheue-Yann Cheng as leading contributors. The journal 'Thyroid' featured the most publications, while the 'Journal of Clinical Endocrinology and Metabolism' ranked highest in citation frequency. Research focused on gene expression analysis and preoperative diagnostics, with recent trends shifting toward prognosis management and machine learning due to advances in medical technology and increased health awareness. CONCLUSION: This comprehensive bibliometric analysis has mapped the landscape of FTC research, highlighting key contributors, institutions, and thematic trends. Current discourse predominantly revolves around genetic analysis, prognostic determinants, and preoperative diagnostics in FTC. This foundational work guides future FTC research, providing insights into its evolution.

A Patient With Hepatocellular Carcinoma and Lung Metastasis Successfully Underwent Curative Surgery Following the Downstaging Treatment: A Case Report.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Hepatic resection constitutes the major curative treatment option, but a significant proportion of patients are not surgical candidates on initial evaluation. Along with the development of novel therapeutic strategies including targeted therapies and immunotherapies, a few HCCs can achieve tumor downstaging and be curatively resected. A 52-year-old man was diagnosed with HCC with portal vein invasion and extensive pulmonary and lymph node metastasis. Transarterial chemoembolization (TACE) in conjunction with donafenib and sintilimab was given. Primary tumors in the liver largely shrank with almost complete elimination of the lung metastases following treatment. The patient subsequently underwent curative surgery for HCC, and the pathological examination revealed complete necrosis of the tumor. Targeted immunotherapy was continued after surgery and no disease progression was found on the latest follow-up. Advanced HCC with distant metastasis might have an excellent response to combination therapy of TACE with tyrosine kinase-targeted inhibitors and PD-1 blocker, and achieve opportunity for curative surgery. This efficacy may be associated with the remodeling of immune microenvironment and angiogenesis. HCC is extremely heterogeneous, and the response to therapeutics varies among patients. There is a lack of useful biomarkers to predict therapeutic efficacy, which needs further studies.

Impact of different categories of intermediate risk factors on the recurrence of papillary thyroid carcinoma: a retrospective cohort study.

BACKGROUND: Data regarding the long-term recurrence in patients with intermediate-risk papillary thyroid carcinoma (PTC) are limited. The aim of this study was to assess the impact of primary tumor-related risk factors and lymph node (LN)-only risk factors on recurrence-free survival (RFS) in patients with intermediate-risk PTC. MATERIALS AND METHODS: Patients with PTC who received initial treatment at our institution between 2010 and 2016 were retrospectively reviewed. A total of 799 intermediate-risk PTC patients were included and further categorized into subgroups according to the different categories of intermediate risk factors. The RFS rates of these subgroups were investigated and compared. RESULTS: Structural recurrence developed in 11 patients (1.4%) of the whole cohort during a median follow-up duration of 96 months. There were no significant differences in RFS between the primary tumor-only risk group and the LN-only risk group, while the combined group of primary tumor risk factors and LN risk factor (metastatic LNs >5) was associated with a worse RFS rate. In the matched-pair analysis, no significant difference in RFS was found between patients who underwent thyroid lobectomy (TL) and those who underwent total thyroidectomy (TT) (6-year RFS: 99.6% vs. 98.8%, P = 0.316) during a median follow-up duration of 100 months. CONCLUSIONS: Intermediate-risk PTC patients who underwent TL had a comparable RFS to those who underwent TT. The combination of primary tumor risk factors and LN risk factor (metastatic LNs >5) may be a useful tool for predicting the risk of long-term structural recurrence in patients with intermediate-risk PTC.

Well-defined survival outcome disparity across age cutoffs at 45 and 60 for medullary thyroid carcinoma: a long-term retrospective cohort study of 3601 patients.

Background: Medullary thyroid cancer (MTC) is a challenging malignancy. The survival outcome of MTC based on AJCC staging system does not render a discriminant classifier among early stages. Methods: 3601 MTC patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Smooth curve fitting, Cox proportional hazard regression and competing risk analysis were applied. Results: A linear correlation between age and log RR (relative risk of overall death) was detected. Overlaps were observed between K-M curves representing patients aged 45-50, 50-55, and 55-60. The study cohort was divided into 3 subgroups with 2 age cutoffs set at 45 and 60. Each further advanced age cutoff population resulted in a roughly "5%" increase in MTC-specific death risks and an approximately "3 times" increase in non-MTC-specific death risks. Conclusions: The survival outcome disparity across age cutoffs at 45 and 60 for MTC has been well defined.

Incidental synchronous intrathyroidal parathyroid carcinomas and papillary thyroid microcarcinoma with compressive neck mass and primary hyperparathyroidism: case report and literature review.

BACKGROUND: Parathyroid carcinoma (PC) is a rare malignancy, often diagnosed incidentally through postoperative pathological examination. The occurrence of nodular goiter, intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma (PA), and papillary thyroid microcarcinoma (PTMC) is extremely uncommon, which prompted us to report our case experience. CASE PRESENTATION: We describe a 67-year-old male who presented with a cervical mass causing tracheal compression, which prompted him to seek medical advice. Based on preoperative auxiliary examination results from color Doppler ultrasound, SPECT parathyroid imaging, and blood tests, he was initially diagnosed with a suspected parathyroid adenoma and nodular goiter. Excision of the right lobe and isthmus of the thyroid, and left superior parathyroid gland was conducted, which were sent to intraoperative frozen pathological examination. During intraoperative observation, adhesion around the right thyroid lobe was discovered. Consequently, right central area lymph node dissection was performed due to suspicion of an aggressive malignant tumor. Histology and immunohistochemistry analysis revealed incidental intrathyroidal parathyroid carcinoma, contralateral parathyroid adenoma, classical papillary thyroid microcarcinoma, and nodular goiter. CONCLUSION: Parathyroid carcinoma should be highly suspected when extremely high levels of PTH and severe hypercalcemia are present, which cannot be simply explained by a preoperatively localized parathyroid adenoma, especially when suspicious malignant adhesion is found during intraoperative exploration. In cases where multifocal thyroid nodules are associated with increased uptake of 99Tc-sestamibi, the possibility of coexisting carcinomas should be considered, not only for thyroid malignancy but also for the potential presence of intrathyroidal parathyroid carcinoma.

Fluorogenic Peptide Sensor Array Derived from Angiotensin-Converting Enzyme 2 Classifies Severe Acute Respiratory Syndrome Coronavirus 2 Variants of Concern.

The devastating COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has made society acutely aware of the urgency in developing effective techniques to timely monitor the outbreak of previously unknown viral species as well as their mutants, which could be even more lethal and/or contagious. Here, we report a fluorogenic sensor array consisting of peptides truncated from the binding domain of human angiotensin-converting enzyme 2 (hACE2) for SARS-CoV-2. A set of five fluorescently tagged peptides were used to construct the senor array in the presence of different low-dimensional quenching materials. When orthogonally incubated with the wild-type SARS-CoV-2 and its variants of concern (VOCs), the fluorescence of each peptide probe was specifically recovered, and the different recovery rates provide a "fingerprint" characteristic of each viral strain. This, in turn, allows them to be differentiated from each other using principal component analysis. Interestingly, the classification result from our sensor array agrees well with the evolutionary relationship similarity of the VOCs. This study offers insight into the development of effective sensing tools for highly contagious viruses and their mutants based on rationally truncating peptide ligands from human receptors.

Psychological impacts of lobectomy and total thyroidectomy in PTC measuring 1 to 4 cm with low to intermediate risk of recurrence.

PURPOSE: To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. METHODS: Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. RESULTS: Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. CONCLUSIONS: The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.

TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study.

BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.

The prognostic value of lymph node dissection in patients with parathyroid carcinoma.

Background: Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Methods: Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. Results: The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). Conclusions: PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

In silico analysis of the wild-type and mutant-type of BRCA2 gene.

BACKGROUND: The aim of this study was to conduct an in silico analysis of a novel compound heterozygous variant in breast cancer susceptibility gene 2 (BRCA2) to clarify its structure-function relationship and elucidate the molecular mechanisms underlying triple-negative breast cancer (TNBC). METHODS: A tumor biopsy sample was obtained from a 42-year-old Chinese woman during surgery, and a maxBRCA™ test was conducted using the patient's whole blood. We obtained an experimentally determined 3D structure (1mje.pdb) of the BRCA2 protein from the Protein Data Bank (PDB) as a relatively reliable reference. Subsequently, the wild-type and mutant structures were predicted using SWISS-MODEL and AlphaFold, and the accuracy of these predictions was assessed through the SAVES online server. Furthermore, we utilized a high ambiguity-driven protein-protein docking (HADDOCK) algorithm and protein-ligand interaction profiler (PLIP) to predict the pathogenicity of the mutations and elucidate pathogenic mechanisms that potentially underlies TNBC. RESULTS: Histological examination revealed that the tumor biopsy sample exhibited classical pathological characteristics of TNBC. Furthermore, the maxBRCA™ test revealed two compound heterozygous BRCA2 gene mutations (c.7670 C > T.pA2557V and c.8356G > A.pA2786T). Through performing in silico structural analyses and constructing of 3D models of the mutants, we established that the mutant amino acids valine and threonine were located in the helical domain and oligonucleotide binding 1 (OB1), regions that interact with DSS1. CONCLUSION: Our analysis revealed that substituting valine and threonine in the helical domain region alters the structure and function of BRCA2 proteins. This mutation potentially affects the binding of proteins and DNA fragments and disrupts interactions between the helical domain region and OB1 with DSS1, potentially leading to the development of TNBC. Our findings suggest that the identified compound heterozygous mutation contributes to the clinical presentation of TNBC, providing new insights into the pathogenesis of TNBC and the influence of compound heterozygous mutations in BRCA2.

The EPRS-ATF4-COLI pathway axis is a potential target for anaplastic thyroid carcinoma therapy.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. OBJECTIVE: In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. METHODS: A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. RESULTS: HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-ß-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. CONCLUSION: This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Radioactive iodine therapy improves overall survival outcome in oncocytic carcinoma of the thyroid by reducing death risks from noncancer causes: A competing risk analysis of 4641 patients.

BACKGROUND: Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite. METHODS: 4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. RESULTS: Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%). CONCLUSIONS: RAI therapy can improve survival in OCA by reducing noncancer death risks.

Therapeutic Effects of Lifei Decoction in a Murine Model of COPD Induced by LPS and Cigarette Smoke.

Introduction: The Lifei Decoction (LD) is a commonly utilized Chinese medicine for the treatment of sepsis and bronchial inflammation. However, its therapeutic potential in chronic obstructive pulmonary disease (COPD) remains unknown. Therefore, the objective of this study was to investigate the therapeutic efficacy and underlying mechanism of LD in a mouse model of COPD induced by cigarette smoke (CS) combined with lipopolysaccharide (LPS). Methods: Hematoxylin-eosin (H&E) staining was employed to observe the pathological alterations in lung tissue, while ELISA was utilized for the detection of levels of inflammatory factors in both lung tissue and bronchoalveolar lavage fluid (BALF). Additionally, Western blot analysis was conducted to assess the expression of p-NF-κB, GDF11, ZO-1, and Occludin-1 proteins. The changes in intestinal flora were evaluated using the viable bacteria count method. Results: The administration of LD demonstrates significant efficacy in mitigating pulmonary tissue damage in a murine model, while concurrently inhibiting the activation of the inflammatory pathway NF-κB to attenuate the levels of pro-inflammatory factors. Moreover, LD exhibits the capacity to enhance the expression of intestinal functional proteins ZO-1 and Occludin-1, thereby rectifying dysbiosis within the gut microbiota. Conclusion: The LD shows great promise as a potential treatment for COPD.

Mex-3 RNA binding family member A (MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy.

RNA-binding proteins (RBPs)-RNA networks have contributed to cancer development. Circular RNAs (circRNAs) are considered as protein recruiters; nevertheless, the patterns of circRNA-protein interactions in colorectal cancer (CRC) are still lacking. Processing bodies (PBs) formed through liquid-liquid phase separation (LLPS) are membrane-less organelles (MLOs) consisting of RBPs and RNA. Previous evidence suggests a connection between PBs dynamics and cancer progression. Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs, there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC. Herein, we identify that MEX-3 RNA binding family member A (MEX3A), frequently upregulated in CRC tissues, predicts poorer patient survival. Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells. Importantly, MEX3A undergoes intrinsically disordered regions (IDRs)-dependent LLPS in the cytoplasm. Specifically, circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins. The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A (PDE5A) mRNA degradation, consequently leading to the aggressive properties of CRC cells. Clinically, CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival. Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation, which provides prognostic markers and/or therapeutic targets for CRC.

Constructing 2D Polyphenols-Based Crosslinked Networks for Ultrafast and Selective Uranium Extraction from Seawater.

The role of tannins (TA), a well-known abundant and ecologically friendly chelating ligand, in metal capture has long been studied. Different kinds of TA-containing adsorbents are synthesized for uranium capture, while most adsorbents suffer from unfavorable adsorption kinetics. Herein, the design and preparation of a TA-containing 2D crosslinked network adsorbent (TANP) is reported. The ≈1.8-nanometer-thick TANP films curl up into micrometer-scale pores, which contribute to fast mass transfer and full exposure of active sites. The coordination environment of uranyl (UO2 2+) ions is explored by integrated analysis of U L3-edge XANES and EXAFS. Density functional theory calculations indicate the energetically favorable UO2 2+ binding. Consequently, TANP with excellent adsorption kinetics presents a high uranium capture capacity (14.62 mg-U g-Ads-1) and a high adsorption rate (0.97 mg g-1 day-1) together with excellent selectivity and biofouling resistance. Life cycle assessment and cost analysis demonstrate that TANP has tremendous potential for application in industrial-scale uranium extraction from seawater.

Succinic Acid Ameliorates Concanavalin A-Induced Hepatitis by Altering the Inflammatory Microenvironment and Expression of BCL-2 Family Proteins.

Autoimmune hepatitis (AIH) is a severe immune-mediated inflammatory liver disease that currently lacks feasible drug treatment methods. Our study aimed to evaluate the protective effect of succinic acid against AIH and provide a reliable method for the clinical treatment of AIH. We performed an in vivo study of the effects of succinic acid on concanavalin A (ConA)-induced liver injury in mice. We examined liver transaminase levels, performed hematoxylin and eosin (HE) staining, and observed apoptotic phenotypes in mice. We performed flow cytometry to detect changes in the number of neutrophils and monocytes, and used liposomes to eliminate the liver Kupffer cells and evaluate their role. We performed bioinformatics analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blotting to detect mitochondrial apoptosis-induced changes in proteins from the B-cell lymphoma 2(Bcl-2) family. Succinic acid ameliorated ConA-induced AIH in a concentration-dependent manner, as reflected in the survival curve. HE and TUNEL staining and terminal deoxynucleotidyl transferase dUTP nick end labeling revealed decreased alanine transaminase and aspartate aminotransferase levels, and reduced liver inflammation and apoptosis. RT-qPCR and enzyme-linked immunosorbent assay revealed that succinic acid significantly reduced liver pro-inflammatory cytokine levels. Flow cytometry revealed significantly decreased levels of liver neutrophils. Moreover, the protective effect of succinic acid disappeared after the Kupffer cells were eliminated, confirming their important role in the effect. Bioinformatics analysis, RT-qPCR, and western blotting showed that succinic acid-induced changes in proteins from the Bcl-2 family involved mitochondrial apoptosis, indicating the molecular mechanism underlying the protective effect of succinic acid. Succinic acid ameliorated ConA-induced liver injury by regulating immune balance, inhibiting pro-inflammatory factors, and promoting anti-apoptotic proteins in the liver. This study provides novel insights into the biological functions and therapeutic potential of succinic acid in the treatment of autoimmune liver injury.

Analysis of risk factors for lateral lymph node metastasis in T1 stage papillary thyroid carcinoma: a retrospective cohort study.

Background: The occurrence of cervical lymph node metastasis in T1 stage papillary thyroid carcinoma (PTC) is frequently observed. Notably, lateral lymph node metastasis (LLNM) emerges as a critical risk factor adversely affecting prognostic outcomes in PTC. The primary aim of this investigation was to delineate the risk factors associated with LLNM in the initial stages of PTC. Methods: This retrospective analysis encompassed 3,332 patients diagnosed with T1 stage PTC without evident LLNM at the time of diagnosis. These individuals underwent primary surgical intervention at West China Hospital, Sichuan University between June 2017 and February 2023. The cohort was divided into two groups: patients manifesting LLNM and those without metastasis at the time of surgery. Additionally, T1 stage PTC patients were subdivided into T1a and T1b categories. Factors influencing LLNM were scrutinized through both univariate and multivariate analyses. Results: The incidence of LLNM was observed in 6.2% of the cohort (206 out of 3,332 patients). Univariate analysis revealed significant correlations between LLNM and male gender (P<0.001), tumor localization in the upper lobe (P<0.001), maximal volume of the primary tumor (P<0.001), largest tumor diameter (P<0.001), multifocality (P<0.001), and bilaterality (P<0.001), with the exception of age (P=0.788) and duration of active surveillance (AS) (P=0.978). Multivariate logistic regression analysis identified male gender (P<0.001), upper lobe tumor location (P<0.001), maximal primary tumor volume (P<0.001), and multifocality (P<0.001) as independent predictors of LLNM. However, age categories (≤55, >55 years), maximum tumor diameter, bilaterality, and surveillance duration did not exhibit a significant impact. Comparative analyses between T1a and T1b subgroups showed congruent univariate results but revealed differences in multivariate outcomes. In the T1a subgroup, gender, tumor location, and multifocality (all P<0.05) were associated with elevated LLNM risk. Conversely, in the T1b subgroup, tumor location, dimensions, and multifocality (all P<0.05) were significant predictors of LLNM risk, whereas gender (P=0.097) exerted a marginal influence. Conclusions: The investigation highlights several key risk factors for LLNM in T1 stage PTC patients, including gender, upper lobe tumor location, larger tumor size, and multifocality. Conversely, prolonged AS and younger age did not significantly elevate LLNM risk, suggesting the viability of AS as a strategic option in selected cases.

Psychological impacts of thermal ablation and conventional thyroidectomy in BTN patients: a prospective observational study.

BACKGROUND: Thermal ablation and conventional thyroidectomy are effective therapeutic methods for treating benign thyroid nodules (BTNs), but the psychological impacts of these methods in BTN patients are largely unknown. MATERIALS AND METHODS: This survey study prospectively enrolled patients who were admitted to our hospital between July 2021 and July 2022. The four validated scales were applied to quantify psychological distress and sleep quality at five points (the day admitted to the hospital, the day discharged from the hospital, and 1, 3, and 6 months after treatment). Participants who were diagnosed with BTNs and completed the questionnaires were ultimately enrolled and divided into thermal ablation and conventional thyroidectomy groups. A propensity score matching (PSM) cohort was subsequently developed to evaluate longitudinal and cross-sectional changes in psychological-related indicators. RESULTS: Among 548 eligible BTN patients, 460 patients completed all the questionnaires throughout the follow-up (response rate: 83.94%), including 368 (80.00%) patients who underwent thermal ablation and 92 (20.00%) patients who underwent conventional thyroidectomy. After PSM, a total of 342 patients were enrolled (256 patients underwent thermal ablation, and 86 patients underwent conventional thyroidectomy). The psychological-related indicators of patients in the thermal ablation group remained relatively stable during the 6-month follow-up, but patients in the conventional thyroidectomy group may have experienced greater anxiety and sleep quality concerns in the longitudinal assessment. Additionally, in the cross-sectional evaluation, the sleep quality of the thermal ablation group was also better than that of the conventional thyroidectomy group postoperatively. CONCLUSIONS: Thermal ablation is superior to conventional thyroidectomy for BTN patients in terms of psychological-related indicators.