Expression and Significance of the Long Non-Coding RNA APTR in the Occurrence and Development of Lung Adenocarcinoma.

As one of the three major malignant tumors, lung adenocarcinoma (LUAD), with its rapid progression and high mortality rate, has become the most dangerous factor endangering human health. This study aims to explore new potential molecular targets, explore the regulatory role of lncRNA APTR in LUAD, and provide a more theoretical basis for the selection of LUAD therapeutic targets. The expression of APTR in LUAD was detected by PCR experiments, and the relationship between APTR and patients' clinical conditions and prognosis was analyzed by chi-square test, multifactor Cox regression, and Kaplan-Meier. The interaction between APTR and miR-298 and the regulation of LUAD cellular activities by APTR/miR-298 were explored by the luciferase reporter gene system. APTR expression was found to be upregulated in LUAD tissues and cells, and the expression of APTR was revealed to be substantially linked with lymph node metastases and TNM stage. High expression of LUAD also predicted a poor prognosis for patients. Downregulation of APTR expression significantly inhibited the activities of LUAD cells. In addition, APTR targeted miR-298 and negatively regulated miR-298 expression. The inhibitory effect of APTR knockdown on LUAD cell activity was also reversed after transfection with miR-298 inhibitor. Increasing expression of APTR is associated with patients' poor prognosis, APTR targets miR-298 and promotes LUAD cellular activity through negative regulation of miR-298.

Bone marrow mesenchymal stem cells-derived exosomal miR-381 alleviates lung ischemia-reperfusion injury by activating Treg differentiation through inhibiting YTHDF1 expression.

AIM: Our study aimed to investigate whether BMSCs-derived exosomal miR-381 promotes Treg cell differentiation in lung ischemia-reperfusion injury (LIRI), and the underlying mechanism. METHODS: The in vitro and in vivo models of LIRI were established by hypoxia/reoxygenation (H/R) treatment and lung ischemia/reperfusion (I/R) surgery, respectively. BMSCs-derived exosomes were isolated and identified by western blot, nanoparticle tracking analysis, and transmission electron microscopy. Cell viability, proliferation, and apoptosis were assessed by CCK-8, EdU, and flow cytometry assay, respectively. IL-18 secretion level in lung microvascular endothelial cells (LMECs) and lung tissue homogenate was examined by ELISA. Treg cell differentiation was determined using flow cytometry. The relationships between miR-381, YTHDF1, and IL-18 were investigated using dual-luciferase reporter gene, RIP, and/or RNA pull-down assays. MeRIP assay was employed to determine m6A modification of IL-18 mRNA in LMECs. The ubiquitination level of Foxp3 protein in CD4+ T cells was analyzed by Co-IP assay. RESULTS: BMSCs-derived exosomes reduced LMECs injury and increased Treg cell differentiation in LIRI, whereas miR-381 inhibition in BMSCs weakened these impacts. Mechanistically, miR-381 inhibited IL-18 translation in LMECs by inhibiting YTHDF1 expression via binding to its 3'-UTR. As expected, YTHDF1 overexpression in LMECs abolished the effects of miR-381-overexpressed exosomes on LMECs injury and Treg cell differentiation. Moreover, LMECs-secreted IL-18 inhibited Treg cell differentiation by promoting the ubiquitination degradation of Foxp3 protein. CONCLUSION: BMSCs-derived exosomal miR-381 suppressed IL-18 translation in LMECs through binding to YTHDF1 3'-UTR, thus suppressing the ubiquitination degradation of Foxp3 in CD4+ T cells, which promoted Treg cell differentiation and mitigated LIRI development.

Helicobacter pylori CagA mediated mitophagy to attenuate the NLRP3 inflammasome activation and enhance the survival of infected cells.

Helicobacter pylori (H. pylori) is one of the most common bacterial infections in the world, and its key virulence component CagA is the leading cause of gastric cancer. Mitophagy is a form of selective autophagy that eliminates damaged mitochondria and is essential for some viruses and bacteria to evade the immune system. However, the mechanisms by which CagA mediates H. pylori-induced mitophagy and NLRP3 inflammasome activation remain elusive. In this study, we reported that H. pylori primarily uses its CagA to induce mitochondrial oxidative damage, mitochondrial dysfunction, dynamic imbalance, and to block autophagic flux. Inhibition of mitophagy led to an increase in NLRP3 inflammasome activation and apoptosis and a decrease in the viability of H. pylori-infected cells. Our findings suggested that H. pylori induces mitochondrial dysfunction and mitophagy primarily via CagA. It reduces NLRP3 inflammasome activation to evade host immune surveillance and increases the survival and viability of infected cells, potentially leading to gastric cancer initiation and development. Our findings provide new insights into the pathogenesis of H. pylori-induced gastric cancer, and inhibition of mitophagy may be one of the novel techniques for the prevention and treatment of this disease.

The overall and smoking-attributable burden of multiple sclerosis among older adults aged 65-89 years from 1990 to 2019 and predictions to 2040.

Background: The global prevalence of aging individuals with multiple sclerosis (MS) is increasing. This study aimed to assess the burden and trends of overall and smoking-attributable MS in older adults aged 65-89 years at the global, regional, and national levels. Methods: The number and rates of years of life lived with disability (YLD) and years of life lost (YLL) due to MS for older adults in 204 countries and territories from 1990 to 2019 were retrieved from the Global Burden of Disease (GBD) Study 2019. Estimated annual percentage change (EAPC) in the age-standardized YLD and YLL rates were calculated to quantify the temporal trends. The Bayesian age-period-cohort model was used to predict the trends from 2020 to 2040. Results: In 2019, there were an estimated 80,040 (95% uncertainty interval 57,534 to 103,608) YLD and 139,132 (107,632 to 161,172) YLL caused by MS among older adults globally. The age-standardized YLD and YLL rates decreased by an average of -0.21% (95% CI -0.26 to -0.16) and - 0.2% (95% CI -0.26 to -0.14) per year for overall MS from 1990 to 2019, respectively. The number of YLL globally in 2019 was 7,891 (5,003 to 10,991) and 15,667 (10,833 to 20,076) due to smoking-attributable MS. The age-standardized YLD and YLL rates decreased by an annual average of -1.14% (95% CI -1.25 to -1.04) and - 1.15% (95% CI -1.27 to -1.03) for MS attributable to smoking. Although the global age-standardized rates of YLD and YLL for MS among older adults declined from 1990 to 2019, many regions showed increases. The largest increase in age-standardized YLD rate of MS was observed in East Asia (average annual change 1.62% [95% CI: 1.56 to 1.68]), while the largest increase in the age-standardized YLL rate occurred in High-income North America (1.74% [1.53 to 1.96]). Nationally, the age-standardized YLD and YLL rates for overall and smoking-attributable MS increased exponentially with increases in SDI level (all model p < 0.001). Furthermore, projections have also indicated an expected decrease in the age-standardized rates of YLD and YLL of MS in the elderly population from 2020 to 2040. Conclusion: Tracking trends in MS burden among older adults provides insights into the potential shifts in disease patterns over time. The findings lay the groundwork for informed decision-making in public health and healthcare delivery, aiming to ensure that older adults with MS receive appropriate care and support.

Leveraging cfDNA fragmentomic features in a stacked ensemble model for early detection of esophageal squamous cell carcinoma.

In this study, we develop a stacked ensemble model that utilizes cell-free DNA (cfDNA) fragmentomics for the early detection of esophageal squamous cell carcinoma (ESCC). This model incorporates four distinct fragmentomics features derived from whole-genome sequencing (WGS) and advanced machine learning algorithms for robust analysis. It is validated across both an independent validation cohort and an external cohort to ensure its generalizability and effectiveness. Notably, the model maintains its robustness in low-coverage sequencing environments, demonstrating its potentials in clinical settings with limited sequencing resources. With its remarkable sensitivity and specificity, this approach promises to significantly improve the early diagnosis and management of ESCC. This study represents a substantial step forward in the application of cfDNA fragmentomics in cancer diagnostics, emphasizing the need for further research to fully establish its clinical efficacy.

Unusual cadinane-involved sesquiterpenoid dimers from Artemisia annua and their antihepatoma effect.

Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 µg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 â†’ 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values ranging from 30.5 to 57.2 µM.

Diverse functions of Tribbles homolog 3 in cancers and its potential as a therapeutic target.

Currently, cancer is the second leading cause of death worldwide, and potential targeted drugs and molecular pathways for cancer development and progression have been a hot research topic worldwide. In recent years, the importance of the kinase superfamily in diseases has been well demonstrated by studies on various molecular mechanisms of kinases and the successful application of their inhibitors in diseases. Pseudokinases are members of the kinase superfamily, which have been increasingly documented to play a crucial role in cancers year after year. As a member of pseudokinases, tribbles homolog 3 (TRIB3) also exerts diverse functions in different cancers through different interacting proteins and molecular pathways, especially in tumor immunity, stemness, drug resistance, metabolism, and autophagy. In addition, peptide drugs targeting TRIB3 have high specificity in preclinical studies, which shows great promise for TRIB3 application in diseases including cancers. In this review, we dissect diverse functions played by TRIB3 in different cancers, describing the underlying mechanisms in detail. Notably, inhibitors and agonists currently available for TRIB3 are discussed, indicating the potential for TRIB3 as a therapeutic target.

The global burden and trends analysis of early-onset colorectal cancer attributable to dietary risk factors in 204 countries and territories, 1990-2019: a secondary analysis for the global burden of disease study 2019.

Background: Rising trends in early-onset colorectal cancer (CRC) burden have been observed, but the distribution and temporal patterns of early-onset CRC attributable to dietary risks remain unclear. Objectives: This study aimed to estimate the burden of early-onset CRC attributable to dietary risk factors globally, regionally, and nationally, by age and sex, from 1990 to 2019. Methods: The absolute number and age-specific rates (ASR) of diet-related early-onset CRC burden, as well as summary exposure value (SEV) of attributable dietary risk factors, were extracted from the Global Burden of Disease (GBD) Study 2019. The temporal changes in the burden between 1990 and 2019 were analyzed by calculating the percentage change in the absolute number of burden and the estimated annual percentage change (EAPC) in ASR of burden. The annualized rates of change (ARC) were calculated to evaluate the variation trend of SEV. Results: In 2019, diet-related early-onset CRC caused 30,096 (95% UI: 23,148 to 36,091) death cases and 1,465,755 (95% UI: 1,126,489 to 1,761,661) DALYs worldwide, accounting for 34.8% deaths and 34.4% DALYs of overall early-onset CRC, respectively. Moreover, a diet low in milk (responsible for 16.5% [95% UI: 11.1 to 21.9%] of DALYs in 2019), low in whole grains (15.2% [95% UI: 5.9 to 19.9%]), low in calcium (14.3% [95% UI: 10.7 to 18.9%]), high in red meat (5.3% [95% UI: 1.7 to 9.5%]), high in processed meat (2.5% [95% UI: 0.9 to 4.0%]), and low in fiber (2.3% [95% UI: 0.9 to 4.2%]) were early-onset CRC attributable dietary risk factors. The age-specific DALYs rate of early-onset CRC attributable to each dietary risk factor generally showed an increasing trend globally between 1990 and 2019, except for low intake of fiber (EAPC = -0.57, 95% CI: -0.76 to -0.38). In addition, from 1990 to 2019, males have a higher burden than females and this gap may continue to widen due to the increasing difference between the sexes in most dietary risk factors. Furthermore, dietary risks-attributable early-onset CRC burden has shifted from regions with high socio-demographic index (SDI) to high-middle and middle SDI quintiles with uncontrolled dietary risks. Conclusion: Early-onset CRC remains a concerning issue globally, and effective prevention and modification of dietary risk factors holds great promise to reduce early-onset CRC-related burden. Prioritizing diet improvement for males is critical and urgent for CRC control efforts, particularly for those living in developing countries with ongoing dietary pattern transition.

A prominent role of LncRNA H19 in H. pylori CagA induced DNA damage response and cell malignancy.

Helicobacter pylori (H. pylori), together with its CagA, has been implicated in causing DNA damage, cell cycle arrest, apoptosis, and the development of gastric cancer. Although lncRNA H19 is abundantly expressed in gastric cancer and functions as a pro-oncogene, it remains unclear whether lncRNA H19 contributes to the oncogenic process of H. pylori CagA. This study investigates the role of H19 in the DNA damage response and malignancy induced by H. pylori. It was observed that cells infected with CagA+ H. pylori strain (GZ7/cagA) showed significantly higher H19 expression, resulting in increased γH2A.X and p-ATM expression and decreased p53 and Rad51 expression. Faster cell migration and invasion was also observed, which was reversed by H19 knockdown in H. pylori. YWHAZ was identified as an H19 target protein, and its expression was increased in H19 knockdown cells. GZ7/cagA infection responded to the increased YWHAZ expression induced by H19 knockdown. In addition, H19 knockdown stimulated cells to enter the G2-phase and attenuated the effect of GZ7/cagA infection on the cellular S-phase barrier. The results suggest that H. pylori CagA can upregulate H19 expression, participate in the DNA damage response and promote cell migration and invasion, and possibly affect cell cycle arrest via regulation of YWHAZ.

Syringic Acid Attenuates the IL-1ß-Induced Akt Pathway in Chondrocyte ATDC5 Cells.

BACKGROUND: Osteoarthritis (OA) is a chronic progressive joint ailment that is largely predominant worldwide. However, it typically gets worse over time, occurs more frequently, and becomes more crippling. OBJECTIVES: Syringic acid (SA) is a well-known phenolic compound reported to suppress inflammation, cell proliferation, and apoptosis of various cancer cells. Since the role of SA in OA remains unknown, there is a need to hypothesize the anti-inflammatory activities of SA on IL- 1ß-induced ATDC5 chondrocyte­like cells and to elucidate its protective action against OA. METHODS: The cytotoxicity, inflammatory mediators, mRNA expression of MMPs, ADAMTS, COX-2, and Akt/NF-κB protein expression of SA activity on ATDC5 cells were examined through CCK-8 assay, ELISA, RT-qPCR, and western blot. It was found that SA (10, 20, and 30 µM) did not show any inhibitory effects on the viability of the ATDC5 cells in a concentrationdependent manner. RESULTS: SA markedly reduced the inflammatory mediators, cytokines, PGE2, MMPs, COX-2, and ADAMTS in a concentration-dependent manner. Likewise, SA expressively attenuated IL- 1ß-stimulated Akt phosphorylation and NF-κB activation as well as IL-1ß- induced ATDC5 chondrocytes. CONCLUSION: This study revealed that SA is a novel candidate applicable for the treatment of OA.

Global, regional, and national burden and trends analysis of gallbladder and biliary tract cancer from 1990 to 2019 and predictions to 2030: a systematic analysis for the Global Burden of Disease Study 2019.

Objectives: Our aim was to explore the disease burden caused by gallbladder and biliary tract cancer globally, regionally, and nationally, by age and sex. Methods: The absolute number of cases and age-standardized rates (ASR) of incidence, prevalence, mortality, and disability-adjusted life years (DALYs) due to gallbladder and biliary tract cancer were extracted from the Global Burden of Disease (GBD) Study 2019. We estimated the trends in disease burden by calculating the percentage change in the absolute number of cases and the estimated annual percentage change (EAPC) in ASR, by social development index (SDI), region, nation, sex, and age. Results: From 1990 to 2019, the number of incident cases, prevalent cases, deaths, and DALYs worldwide significantly increased by 1.85-fold, 1.92-fold, 1.82-fold, and 1.68-fold, respectively. However, the age-standardized rates of incidence, prevalence, mortality, and DALYs tend to decrease globally over time. Nevertheless, heterogeneous disease burden patterns exist between geographic regions due to different geographical risk factors, distinct epidemiologically predominant gallbladder and biliary tract cancer subtypes, and potential genetic predispositions or ethnicity. Additionally, socioeconomic status mediates the regional variation in disease burden, with increasing SDI or HDI scores associated with downward trends in the age-standardized rates of incidence, prevalence, mortality, and DALYs. Older individuals and females are at higher risk of gallbladder and biliary tract cancer, but the increasing burden of early-onset gallbladder and biliary tract cancer is a cause for concern, especially for those living in lower SDI areas and males. High BMI is the primary risk factors underlying gallbladder and biliary tract cancer, accounted for 15.2% of deaths and 15.7% DALYs globally in 2019. Conclusion: Our study comprehensively elucidated the distribution and dynamic trends of gallbladder and biliary tract cancer burden over the past three decades, from multiple dimensions. These findings emphasize the importance of promoting a healthy lifestyle as a population-level cancer prevention strategy and tailoring cancer control actions based on localized risk factors and the epidemic profiles of gallbladder and biliary tract cancer by anatomical subtype.

Transarterial Chemoembolization with Epirubicin-Loaded Microspheres for Hepatocellular Carcinoma: A Prospective, Single-Arm, Multicenter, Phase 2 Study (STOPPER Trial).

PURPOSE: While the role of drug-eluting beads transarterial chemoembolization (DEB-TACE) for hepatocellular carcinoma (HCC) is established, questions regarding appropriate bead size for use in patients remain. This trial evaluated the effectiveness and safety of DEB-TACE using small-size (≤ 100 µm) microspheres loaded with epirubicin. MATERIALS AND METHODS: This prospective, single-arm, multicenter study enrolled patients diagnosed with HCC who underwent DEB-TACE using 40 (range, 30-50), 75 (range, 60-90), or 100 (range, 75-125) µm epirubicin-loaded microspheres (TANDEM microspheres, Varian Medical). Bead size was at the discretion of treating physicians and based on tumor size and/or vascular structure. The primary outcome measure was 6-month objective response rate (ORR). Secondary outcome measures were 30-day and 3-month ORR, time to tumor progression and extrahepatic spread, proportion of progression-free survival and overall survival (OS) at one year, and incidence of treatment-associated adverse events. RESULTS: Data from 108 patients from ten centers was analyzed. Six-month ORR was 73.3 and 71.3% based on European association for the study of the liver (EASL) and modified response evaluation criteria in solid tumors (mRECIST) criteria, respectively. Thirty-day ORR was 79.6% for both EASL and mRECIST criteria with 3-month ORR being 80.0 and 81.0%, respectively, for each criteria. One-year PPF and OS rate were 60.3 and 94.3%. There was a total of 30 SAEs reported to be likely to definitely associated with microsphere (n = 9), epirubicin (n = 9), or procedure (n = 12) with none resulting in death. CONCLUSION: DEB-TACE using epirubicin-loaded small-sized (≤ 100 µm) microspheres demonstrates promising local tumor control and acceptable safety in patients with HCC. TRIAL REGISTRATION: Clinicaltrials.gov NCT03113955; registered April 14, 2017. Trial Registration Clinicaltrials.gov NCT03113955; registered April 14, 2017. LEVEL OF EVIDENCE: 2, Prospective, Non-randomized, Single-arm, study.

Clinical application of optical and electromagnetic navigation system in CT-guided radiofrequency ablation of lung metastases.

PURPOSE: To evaluate the clinical value of CT-guided radiofrequency ablation (RFA) in the diagnosis and treatment of pulmonary metastases under optical and electromagnetic navigation. METHODS: Data on CT-guided radiofrequency ablation treatment of 93 metastatic lung lesions in 70 patients were retrospectively analyzed. There were 46 males and 24 females with a median age of 60.0 years (16-85 years). All lesions were ≤3cm in diameter. 57 patients were treated with 17 G radiofrequency ablation needle puncture directly ablated the lesion without biopsy, and 13 patients were treated with 16 G coaxial needle biopsy followed by radiofrequency ablation. There were 25 cases in the optical navigation group, 25 in the electromagnetic navigation group, and 20 in the non-navigation group. The navigation group was performed by primary interventionalists with less than 5 years of experience, and the non-navigation group was performed by interventionalists with more than 5 years of experience. RESULT: All operations were successfully performed. There was no statistically significant difference in the overall distribution of follow-up results among the optical, electromagnetic, and no navigation groups. Complete ablation was achieved in 84 lesions (90.3%). 7 lesions showed incomplete ablation and were completely inactivated after repeat ablation. 2 lesions progressed locally, and one of them still had an increasing trend after repeat ablation. No serious complications occurred after the operation. CONCLUSIONS: Treatment with optical and electromagnetic navigation systems by less experienced operators has similar outcomes to traditional treatments without navigational systems performed by more experienced operators.

Highly oxygenated guaiane-type sesquiterpene lactones from Artemisia sacrorum and their antihepatoma activity.

The ethanol and EtOAc extracts of Artemisia sacrorum exhibited inhibitory effect against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 65.5%, 28.1%, 84.6%, and 93.5%, 82.0%, 89.0% at 200 µg/mL. Twenty-three undescribed guaiane-type sesquiterpene lactones, artemisacrolides A‒W, were isolated from A. sacrorum under the guidance of antihepatoma activity. Their structures were elucidated by spectral data (HRESIMS, IR, UV, 1D and 2D NMR), ECD calculations, and a single-crystal X-ray diffraction. Artemisacrolides A‒U were guaiane-type sesquiterpene lactones possessing α-methylene-γ-lactone and containing acetoxyl groups at C-8, and artemisacrolides V and W represented the first report from the genus Artemisia with a 1,10-rearranged guaiane-type sesquiterpene lactone. Antihepatoma assay suggested that artemisacrolides A‒U demonstrated better inhibitory activity in Huh7 and SK-Hep-1 cells than those of HepG2 cells. Among them, nine compounds exhibited significant inhibitory activity against Huh7 cells with IC50 values of 8.2-14.3 µM, superior or equal to that of sorafenib; seven compounds demonstrated obvious activity against SK-Hep-1 cells with IC50 values of 13.5-19.2 µM, which were equivalent to that of sorafenib. Artemisacrolides B and E were the most active ones in three human hepatoma cell lines with IC50 values of 21.9, 8.2, 16.9 and 22.6, 9.0, 17.3 µM.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Model containing sarcopenia and visceral adiposity can better predict the prognosis of hepatocellular carcinoma: a multicenter study.

AIM: This study aimed to explore whether the addition of sarcopenia and visceral adiposity could improve the accuracy of model predicting progression-free survival (PFS) in hepatocellular carcinoma (HCC). METHODS: In total, 394 patients with HCC from five hospitals were divided into the training and external validation datasets. Patients were initially treated by liver resection or transarterial chemoembolization. We evaluated adipose and skeletal muscle using preoperative computed tomography imaging and then constructed three predictive models, including metabolic (ModelMA), clinical-imaging (ModelCI), and combined (ModelMA-CI) models. Their discrimination, calibration, and decision curves were compared, to identify the best model. Nomogram and subgroup analysis was performed for the best model. RESULTS: ModelMA-CI containing sarcopenia and visceral adiposity had good discrimination and calibrations (integrate area under the curve for PFS was 0.708 in the training dataset and 0.706 in the validation dataset). ModelMA-CI had better accuracy than ModelCI and ModelMA. The performance of ModelMA-CI was not affected by treatments or disease stages. The high-risk subgroup (scored > 198) had a significantly shorter PFS (p < 0.001) and poorer OS (p < 0.001). CONCLUSIONS: The addition of sarcopenia and visceral adiposity improved accuracy in predicting PFS in HCC, which may provide additional insights in prognosis for HCC in subsequent studies.

Association between the ESR1 and ESR2 polymorphisms and osteoporosis risk: An updated meta-analysis.

BACKGROUND: Gene polymorphisms of estrogen receptor (ESR) 1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), and RsaI (rs1256049) had been reported to be associated with the risk of osteoporosis. However, these conclusions were inconsistent, therefore, an updated meta-analysis was conducted to further explore these issues. OBJECTIVE: To evaluate the association between gene polymorphisms of ESR1 PvuII (rs2234693), XbaI (rs9340799), G2014A (rs2228480), ESR2 AluI (rs4986938), RsaI (rs1256049), and osteoporosis risk. MATERIALS AND METHODS: PubMed, Medline, Ovid, Embase, CNKI, and China Wanfang databases were searched. Association was assessed using odds ratio with 95% confidence interval. Moreover, the false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria were used to assess the credibility of statistically significant associations. RESULTS: Overall, ESR1 PvuII (rs2234693) and XbaI (rs9340799) were associated with the risk of osteoporosis in Indians. Moreover, ESR1 G2014A (rs2228480) was associated with the decreased risk of osteoporosis in East Asians. Moreover, ESR2 Alul (rs4986938) was associated with the increased risk of osteoporosis in East Asians and Caucasians. There was a significant association between ESR2 Rsal (rs1256049) and osteoporosis risk in overall population. When only high-quality and Hardy-Weinberg equilibrium studies were included in the sensitivity analysis, all results did not change in the present study. When the credibility was evaluated applying false-positive reporting probability, Bayesian false-finding probability, and Venetian criteria, all significant associations were considered as false positive results. CONCLUSIONS: In summary, this study shows that all substantial associations between gene polymorphisms of ESR1 (PvuII, XbaI, and G2014A) and ESR 2 (AluI and RsaI) and osteoporosis risk are possibly false positive results instead of real associations or biological variables.

Internet-Based Self-Help Mindful Self-Compassion Intervention for Parents of Children With Cancer: A Pilot Study.

BACKGROUND: Parents of children with cancer may experience persistent psychological distress and impaired physical health throughout their children's diagnosis and treatment. OBJECTIVE: This study aimed to develop a mindful self-compassion program for parents of children with cancer and explore its effect. METHODS: This pre-post-test study without a control group was conducted with 34 Chinese parents of children with cancer, using mixed methods. Participants received a 6-week internet-based self-help mindful self-compassion intervention. Self-compassion, post-traumatic stress symptoms, depression, and sleep quality were measured at baseline and at 10 weeks post-baseline. Semi-structured interviews were conducted with 9 completers within 10 days after the intervention was completed. RESULTS: Significant differences were observed in self-compassion, re-experiencing, physical depressive symptoms, and sleep quality. Two participants reported feeling miserable or recalling distressing experiences, of which one withdrew from the study while the other completed the intervention. CONCLUSION: The program could improve self-compassion, re-experiencing, physical depressive symptoms, and sleep quality in parents of children with cancer, which demonstrated the feasibility of delivering a self-help mindful self-compassion intervention through the internet. Increasing retention rates in future studies merits further discussion.

Mapping research trends of transarterial chemoembolization for hepatocellular carcinoma from 2012 to 2021: A bibliometric analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the second leading cause of cancer-related deaths. Transcatheter arterial chemoembolization (TACE) is a therapy where drugs aimed to slow or halt tumor development are injected into the artery supplying for HCC tissues. A comprehensive analysis of all the articles on TACE for HCC can give us a general understanding of the progress in this field and provide guidance for future research. AIM: To analyze and visualize scientific results and research trends in TACE treatment for HCC. METHODS: The "Web of Science" database was used to identify articles regarding TACE for the treatment of HCC from 2012 to 2021. VOSviewer and CiteSpace were used to analyze the publications trends, collaboration between countries/insti-tutions/authors, and the co-occurrence of keywords, keyword bursts, and references. RESULTS: A total of 5728 original articles on TACE for HCC were retrieved. Regarding the volume of publications, the total number of yearly publications showed a generally increasing trend. China had the highest number of articles, while the United States achieved the highest Hirsch index and highest number of citations. The Sun Yat-sen University in China was most prolific institution. The most active author was Park, J.W from South Korea. The Journal of Vascular and Interventional Radiology (234 articles) was the most productive journal. There is a growing trend toward international collaboration in TACE for HCC. Cluster networks of co-cited references suggested that practice guidelines and targeted therapies are an essential theme in this field. In addition, cluster analysis based on keyword co-occurrence identified the research topic "prediction of TACE treatment" as a hotspot, and propensity score matching can be used to help investigators conduct innovative studies in the future. CONCLUSION: The results of our bibliometric analysis provide the latest trends and hot topics in TACE therapy for HCC.

Artemongolins A-K, undescribed germacrane-guaiane sesquiterpenoid dimers from Artemisia mongolica and their antihepatoma activities.

Artemongolins A-K (1-11), which are undescribed sesquiterpenoid dimers, were obtained from Artemisia mongolica and characterized through comprehensive spectral data, including HRESIMS, IR, 1D and 2D NMR, and ECD calculations. The absolute configurations of compounds 1, 4, and 7 were undoubtedly determined by a single-crystal X-ray crystallography. Artemongolins A-K (1-11) featured a rare 5/7/5/5/5/10 hexacyclic system composed of a germacrene and a guaianolide by a fused 2-oxaspiro[4,4]nonane-1-one ring system. Antihepatoma evaluation against three human hepatoma cell lines demonstrated that the most active compounds 5 and 6 displayed inhibitory activity with IC50 values of 88.6 and 57.0 (HepG2), 59.1 and 26.4 (Huh7), and 67.5 and 32.5 (SK-Hep-1) µM, respectively.