TLK2 promotes progression of hepatocellular carcinoma through Wnt/ß-catenin signaling.

Background: Hepatocellular carcinoma is a widespread cancer worldwide, ranking as the fifth most frequent cancer and the fourth leading cause of cancer-related deaths. According to comprehensive research, TLK2, a phosphorylated kinase, has been discovered to play a crucial role in promoting tumor development. However, the prognostic significance and influence of TLK2 on hepatocellular carcinoma tumor cells and the immune microenvironment remain unexplored, warranting further investigation. The aim of this study was to investigate the role of TLK2 in promoting the development of hepatocellular carcinoma. Methods: The present study utilized The Cancer Genome Atlas (TCGA) database and other databases as training sets to examine the expression of TLK2 and its prognostic significance. The findings were subsequently validated through cell proliferation assays and cell colony assays. Gene set enrichment analysis (GSEA) was employed to investigate the tumor-related biological processes associated with TLK2 in hepatocellular carcinoma, while the relationship between TLK2 expression and Wnt/ß-catenin signaling pathway was analyzed via TCGA dataset analysis. Western blotting and immunofluorescence assays were used to confirm the experimental results. Results: TLK2 showed higher expression levels in tumor tissues than in normal tissues. Alpha fetoprotein (AFP), T stage, pathological stage, and histological grade were significantly associated with TLK2 expression. High TLK2 expression correlated with worse overall survival (OS) [hazard ratio (HR) =1.62, 95% confidence interval (CI): 1.14-2.29, P=0.007], progression-free survival (PFS) (HR =1.88, 95% CI: 1.40-2.52, P<0.001) and disease specific survival (DSS) (HR =1.86, 95% CI: 1.18-2.93, P=0.007) in the training and validation sets. Both univariate and multivariate analyses showed that TLK2 was an independent prognostic factor. GSEA showed that TLK2 was significantly enriched in tumor-related biological processes. TLK2 induced the activation of ß-catenin signaling, resulting in sustained tumor growth. Methyl thiazolyl tetrazolium (MTT) and colony formation assays demonstrated that TLK2 could promote hepatocellular carcinoma progression. Furthermore, TLK2 showed a significant association with ß-catenin in the Wnt pathway. Conclusions: TLK2 represents an independent prognostic factor in hepatocellular carcinoma and can promote cancer progression via the ß-catenin signaling pathway.

Recurrent Coronary Vasospasm in a 50-Year-Old Woman with Granulomatous Polyangiitis: A Case Report.

Granulomatosis with polyangiitis (GPA) is a necrotizing granulomatous vasculitis classified as an autoimmune small-vessel vasculitis. Clinically, approximately 80% of affected organs in GPA involve the upper/lower respiratory tract and kidneys, with cardiovascular system involvement being rare. Here, we report a case of a 50-year-old female patient who presented with sudden-onset chest pain lasting for 1 hour. The patient had normal body temperature, and markers of infection such as C-reactive protein and erythrocyte sedimentation rate were within normal limits. Electrocardiography revealed ST-segment elevation in inferior, precordial, and posterior leads. Emergency coronary angiography showed no significant obstructive disease, prompting consideration of vasospastic angina given the patient's recurrent chest pain symptoms and findings on laboratory and imaging studies. The patient underwent treatment including coronary vasospasm antagonists and immunomodulation, resulting in clinical improvement and subsequent discharge. During a 7-month follow-up period, the patient did not experience any further adverse cardiovascular events.

Epigenetic regulation of DNA repair gene program by Hippo/YAP1-TET1 axis mediates sorafenib resistance in HCC.

Hepatocellular carcinoma (HCC) is a malignancy that occurs worldwide and is generally associated with poor prognosis. The development of resistance to targeted therapies such as sorafenib is a major challenge in clinical cancer treatment. In the present study, Ten-eleven translocation protein 1 (TET1) was found to be highly expressed in sorafenib-resistant HCC cells and knockdown of TET1 can substantially improve the therapeutic effect of sorafenib on HCC, indicating the potential important roles of TET1 in sorafenib resistance in HCC. Mechanistic studies determined that TET1 and Yes-associated protein 1 (YAP1) synergistically regulate the promoter methylation and gene expression of DNA repair-related genes in sorafenib-resistant HCC cells. RNA sequencing indicated the activation of DNA damage repair signaling was extensively suppressed by the TET1 inhibitor Bobcat339. We also identified TET1 as a direct transcriptional target of YAP1 by promoter analysis and chromatin-immunoprecipitation assays in sorafenib-resistant HCC cells. Furthermore, we showed that Bobcat339 can overcome sorafenib resistance and synergized with sorafenib to induce tumor eradication in HCC cells and mouse models. Finally, immunostaining showed a positive correlation between TET1 and YAP1 in clinical samples. Our findings have identified a previously unrecognized molecular pathway underlying HCC sorafenib resistance, thus revealing a promising strategy for cancer therapy.

Benefit finding among family caregivers of patients with advanced cancer in a palliative treatment: a qualitative study.

BACKGROUND: Benefit finding is the search for positive meaning from traumatic events, such as cancer. It can help caregivers have a positive experience in the caregiving process, relieve negative emotions, and reduce caregiving stress. The aim of this study was to explore benefit finding among caregivers of patients with advanced cancer in their palliative caregiving journey. METHODS: An exploratory qualitative design of phenomenology was used. Semistructured interviews were conducted with 19 caregivers of palliative care patients with advanced cancer. The Colaizzi 7-step analysis was used to analyse, summarize, and extract themes from the interview data. RESULTS: The study identified five themes of caregiver benefit finding in the caregiving process: personal growth, strengthened relationships with patients, adjustment and adaptation, perceived social support, and perceived meaning in life. Most caregivers reported a closer, more dependent relationship with the patient, and only one caregiver did not report any positive changes. CONCLUSIONS: Caregivers of palliative care patients with advanced cancer can have positive experiences in their care. Healthcare professionals should focus on supporting caregivers and helping them find positive experiences to cope with the challenges of caregiving and improve their quality of life.

Mechanistic insights into xanthomicrol as the active anti-HCC ingredient of Phytolacca acinosa Roxb.: A network pharmacology analysis and transcriptomics integrated experimental verification.

ETHNOPHARMACOLOGICAL RELEVANCE: Phytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. AIM OF THE STUDY: The research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Employing network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. RESULTS: Network pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. CONCLUSIONS: Xanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.

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.

[Research progress in surgical treatment of avascular necrosis of talus].

Objective: To summarize the surgical treatment methods for avascular necrosis of the talus. Methods: The recent domestic and international literature related to avascular necrosis of the talus was extensively conducted. The pathogenesis, surgical treatment methods, and prognosis were summarized. Results: The clinical symptoms of avascular necrosis of the talus at early stage are not obvious, and most patients have progressed to Ficat-Arlet stages Ⅲ-Ⅳ and require surgical treatment. Currently, surgical treatments for this disease include core decompression, vascularized bone flap transplantation, arthroplasty, and arthrodesis, etc. Early avascular necrosis of the talus can be treated conservatively, and if treatment fails, core decompression can be considered. Arthrodesis is a remedial surgery for patients with end-stage arthritis and collapse, and in cases of severe bone loss, tibiotalocalcaneal arthrodesis and bone grafting are required. Vascularized bone flap transplantation is effective and plays a role in all stages of avascular necrosis of the talus, but the appropriate donor area for the flap still needs further to be studied. Conclusion: The surgical treatment and the system of treatment for different stages of avascular necrosis of the talus still need to be refined.

Triclocarban and triclosan promote breast cancer progression in vitro and in vivo via activating G protein-coupled estrogen receptor signaling pathways.

Triclocarban (TCC) and triclosan (TCS) have been detected ubiquitously in human body and evoked increasing concerns. This study aimed to reveal the induction risks of TCC and TCS on triple negative breast cancer through non-genomic GPER-mediated signaling pathways. Molecular simulation indicated that TCC exhibited higher GPER binding affinity than TCS theoretically. Calcium mobilization assay displayed that TCC/TCS activated GPER signaling pathway with the lowest observed effective concentrations (LOEC) of 10 nM/100 nM. TCC and TCS also upregulated MMP-2/9, EGFR, MAPK3 but downregulated MAPK8 via GPER-mediated signaling pathway. Proliferation assay showed that TCC/TCS induced 4 T1 breast cancer cells proliferation with the LOEC of 100 nM/1000 nM. Wound-healing and transwell assays showed that TCC/TCS promoted 4 T1 cells migration in a concentration-dependent manner with the LOEC of 10 nM. The effects of TCC on breast cancer cells proliferation and migration were stronger than TCS and both were regulated by GPER. TCC/TCS induced migratory effects were more significantly than proliferative effect. Mechanism study showed that TCC/TCS downregulated the expression of epithelial marker (E-cadherin) but upregulated mesenchymal markers (snail and N-cadherin), which was reversed by GPER inhibitor G15. These biomarkers results indicated that TCC/TCS-induced 4 T1 cells migration was a classic epithelial to mesenchymal transition mechanism regulated by GPER signaling pathway. Orthotopic tumor model verified that TCC promoted breast cancer in-situ tumor growth and distal tissue metastasis via GPER-mediated signaling pathway at human-exposure level of 10 mg/kg/d. TCC-induced tissue metastasis of breast cancer was more significantly than in-situ tumor growth. Overall, we demonstrated for the first time that TCC/TCS could activate the GPER signaling pathways to induce breast cancer progression.

Clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging in benign and malignant renal tumors: A retrospective cohort study.

This study aims to evaluate the clinical diagnostic value of contrast-enhanced ultrasound combined with microflow imaging (CEUS-MFI) in the differential diagnosis of benign and malignant renal tumors. All patients underwent CEUS, MFI, color doppler flow imaging (CDFI), and CEUS-MFI. The efficacies of these different diagnostic modalities in diagnosing benign and malignant renal tumors were evaluated by Kappa consistency test and the receiver operating characteristic (ROC) curve, with pathological findings serving as the gold standard. CDFI, MFI and CEUS-MFI all demonstrated higher blood flow in malignant tumors compared with benign tumors. Compared with benign tumors, CDFI detected a higher rate of punctate and linear Adler grade 2 and 3 blood flows in malignant tumors, as well as peripheral semicircular or annular blood flow. MFI identified a high rate of peripheral circumferential blood flow and irregular vascular morphology in malignant tumors, with most exhibiting Adler grade 3 blood flow. In addition, CEUS-MFI showed more dendritic or irregular Adler grade 2 or 3 blood flows in malignant renal tumors than MFI alone. Further analysis showed that CEUS-MFI had the highest consistency with pathological diagnosis (Kappa = 0.808). The ROC curve showed that the area under the curve (AUC) for CEUS-MFI in differentiating between benign and malignant lesions was 0.898, significantly outperforming other single diagnostic methods. With its capability to display microvascular information and assess overall pathological characteristics, MFI can accurately predict the nature of renal tumors and assist in surgical planning.

Case report: A novel PTCH1 frameshift mutation leading to nevoid basal cell carcinoma syndrome.

A patient presenting with several basal cell carcinomas, pigmented nevi, and developmental defects was diagnosed with nevoid basal cell carcinoma syndrome. Gene panel sequencing and Sanger sequencing were used to identify a novel heterozygous frameshift mutation, c.1312dupA:p.Ser438Lysfs, in exon 9 of PTCH1. I-Tasser and PyMol analyses indicated that the mutated protein patched homolog 1 (PTCH1) lacked 12 transmembrane domains and the intracellular and extracellular rings of ECD2 compared with the wild-type protein, resulting in a remarkably different structure from that of the wild-type protein. This case extends our knowledge of the mutation spectrum of NBCCS.

Enhancing Neuroprotection in Mouse Model of Parkinson's Disease through Protein Nanosystem Conjugation with ApoE Peptide for miR-124 Delivery.

Parkinson's disease (PD) affects millions of people's lives worldwide. The main pathogenesis of PD is dopaminergic neuron necrosis and neuroinflammation mediated by activated microglia cells. In recent years, the anti-inflammatory ability and neuroprotective effects of miR-124 in PD models were well proved, but the in vivo delivery of miR-124 remains challenging. Herein, we report a protein nanosystem modified with a brain-targeting peptide ApoE that could efficiently deliver miR-124 across the blood-brain barrier (BBB). This nanosystem showed good cell viability on brain endothelial cells and microglia cells, and administration of this nanosystem significantly decreased the neuroinflammation and dopaminergic neuron loss, as well as recovered parts of neurobehavioral deficits. This ApoE peptide-based protein nanosystem holds great promise for the delivery of RNA therapeutics to the brain and for realizing neuron protection in PD treatment.

Association and predictive value of contrast­enhanced ultrasound features with axillary lymph node metastasis in primary breast cancer.

Primary breast cancer is the most common malignant tumor in women worldwide, and axillary lymph node metastasis (ALNM) is an important marker of disease progression in patients with breast cancer. The objective of the present study was to analyze the association between contrast-enhanced ultrasound (CEUS) features and ALNM in primary breast cancer and its predictive value. A total of 120 patients with breast cancer were assigned to the non-metastatic group (n=70) and metastatic group (n=50). The factors influencing ALNM were explored by multivariate logistic regression analysis. The consistency of CEUS, ordinary ultrasonography and pathological examination in the diagnosis of the ALNM of breast cancer was evaluated by consistency testing. The sensitivity, specificity and consistency rate of CEUS features and ordinary ultrasonography were analyzed by receiver operating characteristic curve and four-fold table analyses. High enhancement amplitude, centripetal enhancement sequence, increased maximum cortical thickness, high peak intensity and a larger area under the curve of lymph nodes were more commonly found in the metastatic group than in the non-metastatic group. The lymph node aspect ratio and time to peak were lower in the metastatic group than the non-metastatic group. The time to peak was a protective factor for ALNM in patients with breast cancer. The sensitivity, specificity and coincidence rate with pathological examination of CEUS in the diagnosis of ALNM were 92.00, 90.00 and 90.83%, while these of ordinary ultrasonography were 76.00, 80.00 and 78.33%, respectively. The consistency test indicated that CEUS and pathological examination were consistent in the diagnosis of ALNM in patients with breast cancer, with a κ value of 0.816, indicating a good consistency. The κ value of ordinary ultrasonography and pathological examination was 0.763, also indicating a good consistency. However, these results indicate that CEUS is more valuable than ordinary ultrasonography in the diagnosis of ALNM in cases of breast cancer. In conclusion, the present study indicates that CEUS features were influencing factors associated with ALNM in patients with breast cancer and may serve as an important reference for the preoperative prediction of ALNM in breast cancer.

Different Valence States of Copper Ion Delivery against Triple-Negative Breast Cancer.

Different valence states of copper (Cu) ions are involved in complicated redox reactions in vivo, which are closely related to tumor proliferation and death pathways, such as cuproptosis and chemodynamic therapy (CDT). Cu ion mediated Fenton-like reagents induced tumor cell death which presents compelling attention for the CDT of tumors. However, the superiority of different valence states of Cu ions in the antitumor effect is unknown. In this study, we investigated different valence states of Cu ions in modulating tumor cell death by Cu-chelated cyanine dye against triple-negative breast cancer. The cuprous ion (Cu+) and copper ion (Cu2+) were chelated with four nitrogen atoms of dipicolylethylenediamine-modified cyanine for the construction of Cu+ and Cu2+ chelated cyanine dyes (denoted as CC1 and CC2, respectively). Upon 660 nm laser irradiation, the CC1 or CC2 can generate reactive oxygen species, which could disrupt the cyanine structure, achieving the rapid release of Cu ions and initiating the Fenton-like reaction for CDT. Compared with Cu2+-based Fenton-like reagent, the CC1 with Cu+ exhibited a better therapeutic outcome for the tumor due to there being no need for a reduction by glutathione and a shorter route to generate more hydroxyl radicals. Our findings suggest the precision delivery of Cu+ could achieve highly efficient antitumor therapy.

Oligo/polysaccharides from Cyathula officinalis and Achyranthes bidentata: a review of structures and bioactivities.

OBJECTIVES: Oligo-/polysaccharides from Cyathula officinalis Kuan (COPs) and Achyranthes bidentata Blume (ABPs) have attracted researchers' attention in the fields of healthy food supplements and traditional Chinese medicine (Niúxi) due to their multiple bioactivities combined with their nontoxic and highly biocompatible nature. The purpose of this paper was to provide a systematic and comprehensive overview of the extraction, purification, and structural analysis methods, chemical characteristics, biological activities, and structure bioactivity relationship. Furthermore, the possible development trends and perspectives for future research, and traditional uses of Niúxi are also summarized. METHODS: All the information was gathered from a library search and scientific databases. KEY FINDINGS: Although COPs and ABPs are derived from different plants, they have similar structural features in type, structure, and glycosidic linkage patterns and biological activities in vivo and in vitro. However, there are differences in monosaccharide compositions, which can be used as an identification mark. CONCLUSIONS: As traditional Chinese herbal medicine, C. officinalis and A. bidentata have similar pharmacological activities. The COPs and ABP possess wide pharmacological effects such as antitumor, antioxidant, anti-osteoporosis, and anti-inflammatory. Meanwhile, the biological activity and structure-activity relationship of purified COPs and ABPs are less studied, future research should focus on them.

Unveiling Gambogenic Acid as a Promising Antitumor Compound: A Review.

Gambogenic acid is a derivative of gambogic acid, a polyprenylated xanthone isolated from Garcinia hanburyi. Compared with the more widely studied gambogic acid, gambogenic acid has demonstrated advantages such as a more potent antitumor effect and less systemic toxicity than gambogic acid according to early investigations. Therefore, the present review summarizes the effectiveness and mechanisms of gambogenic acid in different cancers and highlights the mechanisms of action. In addition, drug delivery systems to improve the bioavailability of gambogenic acid and its pharmacokinetic profile are included. Gambogenic acid has been applied to treat a wide range of cancers, such as lung, liver, colorectal, breast, gastric, bladder, and prostate cancers. Gambogenic acid exerts its antitumor effects as a novel class of enhancer of zeste homolog 2 inhibitors. It prevents cancer cell proliferation by inducing apoptosis, ferroptosis, and necroptosis and controlling the cell cycle as well as autophagy. Gambogenic acid also hinders tumor cell invasion and metastasis by downregulating metastasis-related proteins. Moreover, gambogenic acid increases the sensitivity of cancer cells to chemotherapy and has shown effects on multidrug resistance in malignancy. This review adds insights for the prevention and treatment of cancers using gambogenic acid.

Gallic acid forms V-amylose complex structure with starch through hydrophobic interaction.

This study aimed to investigate the role of amylose and amylopectin in the formation of starch-polyphenol complex and elucidate the interaction mechanisms. Gallic acid (GA) was used to complex with maize starch with various amylose contents. Results showed GA formed V-type crystals with normal maize starch (NMS) and high amylose maize starch (HAMS), while higher relative crystallinity was exhibited in HAMS-GA complexes than NMS counterparts. Molecular structure analysis revealed more amylose in GA-starch complexes than in treated starch counterparts without GA, and this was more apparent in HAMS than NMS, implying amylose is preferred to complex with GA than amylopectin. FTIR detected higher R1047/1022 value in starch-GA complexes than their starch counterparts without GA, suggesting increased short-range ordered structrure of complexes. Typical signatures of hydrophobic interactions were further revealed by isothermal titration calorimetry, indicating the complexation of GA to starch is mainly through hydrophobic bonds. More binding sites were observed for HAMS (72.50) than NMS (11.33), which proves the preferences of amylose to bind with GA. Molecular dynamics simulated the complexation of GA to amylose, and confirmed hydrophobic bond is the main interaction force. These findings would provide guidance for precise design and utilization of starch-polyphenol complexes in functional foods.

Latent tuberculosis infection in myasthenia gravis patients on immunosuppressive therapy: high incidence yet moderate reactivation rate.

BACKGROUND: Immunosuppressive therapies (ISTs) are mainstays for management of myasthenia gravis (MG). Meanwhile, latent tuberculosis infection (LTBI) is common in the setting of high-burden countries. However, the prevalence of LTBI among MG patients and whether receiving ISTs for MG would aggravate LTBI reactivation remain unknown. METHODS: We retrospectively analyzed the frequency of LTBI via interferon-gamma release assay (IGRA) positivity among hospitalized MG patients from both rural and urban areas in a tertiary hospital, and those receiving ISTs were followed up to investigate the reactivation risk of LTBI. RESULTS: A total of 300 MG patients with determinate IGRA results were enrolled, where the frequency of LTBI was 35.0%. Male (OR = 1.910, 95% CI: 1.181-3.089, p = .008) and elderly (OR = 1.044, 95% CI: 1.027-1.061, p < .001) patients were prone to LTBI. Of those with LTBI, 78 individuals on ISTs were successfully followed up for a median duration of 18.3 (8.5-24.0) months, of which 25 (32.1%) received anti-tuberculosis (TB) treatments. The rate of various degrees of adverse events was 82.1% over the course of the follow-up, but was not different between individuals with and without therapies against TB (χ2 < 0.001, p > .999). Only 1 patient eventually reported lymph node and intestinal TB, with the incidence rate of LTBI reactivation preliminarily estimated to be 0.81 per 100 person years. CONCLUSION: The frequency of LTBI is high in our MG cohort, especially among those with advanced age and males. However, receiving immunosuppressives seems not to increase the risk of LTBI reactivation. LTBI screening is strongly recommended for all MG patients ready to receive ISTs, while preventive anti-TB chemotherapy should be prescribed after weighing potential benefits against the risk of side effects in those with LTBI. In-depth investigation is still entailed to further verify these findings due to the limitation of the retrospective single-center design of our study.

Comparison of gefitinib plus chemotherapy versus gefitinib alone for advanced non-small-cell lung cancer: A meta analysis

Abstract This study aimed to perform a meta-analysis comparing the efficacy and safety of gefitinib in combination with chemotherapy versus gefitinib alone in patients with advanced Non-Small Cell Lung Cancer (NSCLC). We searched databases for clinical studies that reported the efficacy or safety of gefitinib plus chemotherapy in comparison with gefitinib alone. Raw data from included studies were extracted and pooled to calculate the Odds Ratio (OR) for Objective Response Rate (ORR) and Disease Control Rate (DCR), the Hazard Ratio (HR) for Progression-Free Survival (PFS) and Overall Survival (OS), and OR for complication ≥ Grade 3. A total of 10 studies containing 1,528 patients with NSCLC were identified and included in the analysis. Gefitinib plus chemotherapy showed significantly better efficacy in improving ORR (OR = 1.54; 95% CI [Confidence Interval], 1.13‒2.1; p = 0.006), DCR (OR = 1.62; 95% CI 1.14‒2.29; p = 0.007), PFS (HR=1.67; 95% CI 1.45‒1.94; p < 0.001) and OS (HR = 1.49; 95% CI 1.2‒1.87; p < 0.001) as compared with gefitinib alone. Consistent results were observed in the sub-population with positive EGFR mutation. The combination of gefitinib with chemotherapy had a significantly higher risk of complication (≥ Grade 3) with an OR of 3.29 (95% CI 2.57‒4.21; p < 0.001). The findings in the present study suggest that the combination of gefitinib with chemotherapy can provide better disease response and survival outcomes for patients with advanced NSCLC.

Diagnostic models of the pre-test probability of stable coronary artery disease: A systematic review

A comprehensive search of PubMed and Embase was performed in January 2015 to examine the available literature on validated diagnostic models of the pre-test probability of stable coronary artery disease and to describe the characteristics of the models. Studies that were designed to develop and validate diagnostic models of pre-test probability for stable coronary artery disease were included. Data regarding baseline patient characteristics, procedural characteristics, modeling methods, metrics of model performance, risk of bias, and clinical usefulness were extracted. Ten studies involving the development of 12 models and two studies focusing on external validation were identified. Seven models were validated internally, and seven models were validated externally. Discrimination varied between studies that were validated internally (C statistic 0.66-0.81) and externally (0.49-0.87). Only one study presented reclassification indices. The majority of better performing models included sex, age, symptoms, diabetes, smoking, and hyperlipidemia as variables. Only two diagnostic models evaluated the effects on clinical decision making processes or patient outcomes. Most diagnostic models of the pre-test probability of stable coronary artery disease have had modest success, and very few present data regarding the effects of these models on clinical decision making processes or patient outcomes.