Transarterial chemoembolization (TACE) plus tyrosine kinase inhibitors versus TACE in patients with hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC. METHODS: We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs). RESULTS: The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42). CONCLUSIONS: Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings. TRIAL REGISTRATION: PROSPERO registration number: CRD42022298003.

Invasive ductal breast cancer molecular subtype prediction by MRI radiomic and clinical features based on machine learning.

Background: Most studies of molecular subtype prediction in breast cancer were mainly based on two-dimensional MRI images, the predictive value of three-dimensional volumetric features from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for predicting breast cancer molecular subtypes has not been thoroughly investigated. This study aimed to look into the role of features derived from DCE-MRI and how they could be combined with clinical data to predict invasive ductal breast cancer molecular subtypes. Methods: From January 2019 to December 2021, 190 Chinese women with invasive ductal breast cancer were studied (32 triple-negative, 59 HER2-enriched, and 99 luminal lesions) in this institutional review board-approved retrospective cohort study. The image processing software extracted 1130 quantitative radiomic features from the segmented lesion area, including shape-based, first-order statistical, texture, and wavelet features. Three binary classifications of the subtypes were performed: triple-negative vs. non-triple-negative, HER2-overexpressed vs. non-HER2-overexpressed, and luminal (A + B) vs. non-luminal. For the classification, five machine learning methods (random forest, logistic regression, support vector machine, naïve Bayes, and eXtreme Gradient Boosting) were employed. The classifiers were chosen using the least absolute shrinkage and selection operator method. The area evaluated classification performance under the receiver operating characteristic curve, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean. Results: EXtreme Gradient Boosting model showed the best performance in luminal and non-luminal groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.8282, 0.7524, 0.6542, 0.6964, 0.6086, 0.3458, 0.8524 and 0.7016, respectively. Meanwhile, the random forest model showed the best performance in HER2-overexpressed and non-HER2-overexpressed groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.8054, 0.2941, 0.9744, 0.7679, 0.4348, 0.0256, 0.8333 and 0.5353, respectively. Furthermore, eXtreme Gradient Boosting model showed the best performance in the triple-negative and non-triple-negative groups, with AUC, sensitivity, specificity, accuracy, F1-Score, false positive rate, precision, and geometric mean of 0.9031, 0.9362, 0.4444, 0.8571, 0.9167, 0.5556, 0.8980 and 0.6450. Conclusion: Clinical data and three-dimension imaging features from DCE-MRI were identified as potential biomarkers for distinguishing between three molecular subtypes of invasive ductal carcinomas breast cancer. In the future, more extensive studies will be required to evaluate the findings.

Characteristics and quality of clinical practice guidelines addressing acupuncture interventions: a systematic survey of 133 guidelines and 433 acupuncture recommendations.

OBJECTIVE: To systematically summarise acupuncture-related Clinical Practice Guidelines (CPGs)'s clinical and methodological characteristics and critically appraise their methodology quality. DESIGN: We summarised the characteristics of the guidelines and recommendations and evaluated their methodological quality using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument. DATA SOURCES: Nine databases were searched from 1 January 2010 to 20 September 2020. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included the latest version of acupuncture CPGs, which must have used at least one systematic review addressing the benefits and harms of alternative care options to inform acupuncture recommendations. DATA EXTRACTION AND SYNTHESIS: Reviewers, working in pairs, independently screened and extracted data. When there are statistical differences among types of CPGs, we reported the data by type in the text, but when not, we reported the overall data. RESULTS: Of the 133 eligible guidelines, musculoskeletal and connective tissue diseases proved the most commonly addressed therapeutic areas. According to the AGREE II instrument, the CPG was moderate quality in the domain of clarity of scope and purpose, clarity of presentation, the rigour of development, stakeholder involvement and low quality in editorial independence, and applicability. The study identified 433 acupuncture-related recommendations; 380 recommended the use of acupuncture, 28 recommended against the use of acupuncture and 25 considered acupuncture but did not make recommendations. Of the 303 recommendations that used Grading of Recommendations Assessment, Development and Evaluation to determine the strength of recommendations, 152 were weak recommendations, 131 were strong recommendations, of which 104 were supported by low or very low certainty evidence (discordant recommendations). CONCLUSION: In the past 10 years, a large number of CPGs addressing acupuncture interventions exist. Although these guidelines may be as or more rigorous than many others, considerable room for improvement remains.

Accuracy of serological tests for COVID-19: A systematic review and meta-analysis.

Objective: To determine the diagnostic accuracy of serological tests for coronavirus disease-2019 (COVID-19). Methods: PubMed, Embase and the Cochrane Library were searched from January 1 2020 to September 2 2022. We included studies that measured the sensitivity, specificity or both qualities of a COVID-19 serological test and a reference standard of a viral culture or reverse transcriptase polymerase chain reaction (RT-PCR). The risk of bias was assessed by using quality assessment of diagnostic accuracy studies 2 (QUADAS-2). The primary outcomes included overall sensitivity and specificity, as stratified by the methods of serological testing [enzyme-linked immunosorbent assays (ELISAs), lateral flow immunoassays (LFIAs) or chemiluminescent immunoassays (CLIAs)] and immunoglobulin classes (IgG, IgM, or both). Secondary outcomes were stratum-specific sensitivity and specificity within the subgroups, as defined by study or participant characteristics, which included the time from the onset of symptoms, testing via commercial kits or an in-house assay, antigen target, clinical setting, serological kit as the index test and the type of specimen for the RT-PCR reference test. Results: Eight thousand seven hundred and eighty-five references were identified and 169 studies included. Overall, we judged the risk of bias to be high in 47.9 % (81/169) of the studies, and a low risk of applicability concerns was found in 100% (169/169) of the studies. For each method of testing, the pooled sensitivity of the ELISAs ranged from 81 to 82%, with sensitivities ranging from 69 to 70% for the LFIAs and 77% to 79% for the CLIAs. Among the evaluated tests, IgG (80-81%)-based tests exhibited better sensitivities than IgM-based tests (66-68%). IgG/IgM-based CLIA had the highest sensitivity [87% (86-88%)]. All of the tests displayed high specificity (97-98%). Heterogeneity was observed in all of the analyses. The detection of nucleocapsid protein (77-80%) as the antigen target was found to offer higher sensitivity results than surface protein detection (66-68%). Sensitivity was higher in the in-house assays (78-79%) than in the commercial kits (47-48%). Conclusion: Among the evaluated tests, ELISA and CLIA tests performed better in terms of sensitivity than did the LFIA. IgG-based tests had higher sensitivity than IgM-based tests, and combined IgG/IgM test-based CLIA tests had the best overall diagnostic test accuracy. The type of sample, serological kit and timing of use of the specific tests were associated with the diagnostic accuracy. Due to the limitations of the serological tests, other techniques should be quickly approved to provide guidance for the correct diagnosis of COVID-19.

Promoting effect of the Maillard reaction products produced during the stir-frying process of Hordei Fructus Germinatus on the intestinal absorption of active ingredients in Hordei Fructus Germinatus.

This study was designed to evaluate the absorption promoting capacity of Maillard Reaction Products (MRPs) produced during the stir-frying process of Hordei Fructus Germinatus on catechin, ferulic acid, quercetin and kaempferol by the ex vivo rat everted gut sac model, in situ single-pass intestinal perfusion model and the whole animal model. Moreover, verapamil, EDTA and mannitol were used for determining the transport mechanism of catechin, ferulic acid, quercetin and kaempferol. The tight junction (TJ) proteins including zonula occudens-1(ZO-1) and claudin-1 were chosen to investigate the promoting mechanism of MRPs by quantitative real-time PCR (qRT-PCR) and western blot analyses. The results showed that the MRPs produced during the stir-frying process of Hordei Fructus Germinatus could improve the intestinal absorption of catechin, ferulic acid, quercetin and kaempferol. And the absorption-promoting effect of MRPs was related to chelating effect and the reduced expression of claudin-1 and ZO-1. Our results suggested that MRPs could be promising oral absorption promoters, which might be another processing mechanism of Hordei Fructus Germinatus.

IDH2 protects against nonalcoholic steatohepatitis by alleviating dyslipidemia regulated by oxidative stress.

Nonalcoholic fatty liver disease (NAFLD) has become an epidemic across the world. A large and growing unmet therapeutic requirement has inspired plenty exploration in the field. Isocitrate dehydrogenase 2 (IDH2), localized in mitochondria, decreases NADP+ to NADPH during the decarboxylation of isocitrate to α-ketoglutarate. Although the NADPH producing system is closely related to oxidative stress and lipid accumulation, the effects of IDH2 on hepatic steatosis and the associated metabolic disorders remain elusive. In our study, we found that IDH2 expression was markedly reduced by palmitate stimulation in primary hepatocytes, accompanied with increased lipid accumulation. In response to high fat diet (HFD) administration, IDH2 knockout (KO) further contributed to the pathological progression of insulin resistance and hepatic steatosis. In addition, HFD treatment-induced mitochondrial oxidative injury and dyslipidemia were markedly elevated in liver of mice with IDH2 knockout. The expression of mitochondrial fission and fusion mediators, including dynamin-related protein 1 (DRP1), mitofusin 1 (MFN1) and fission protein 1 (FIS1), induced by HFD was further exacerbated in liver of IDH2 knockout mice. Furthermore, the over-expression of IDH2 in hepatocytes led to the suppression of ROS production and DRP1 expression, but the alleviation of dyslipidemia. Taken together, these results established IDH2 as a critical suppressor of steatohepatitis, which might be a promising therapeutic target for developing effective treatment to prevent nonalcoholic steatohepatitis progression.

Up regulated Tmbim1 activation promotes high fat diet (HFD)-induced cardiomyopathy by enhancement of inflammation and oxidative stress.

The prevalence of cardiomyopathy due to metabolic stress has up-regulated dramatically; nevertheless, its molecular mechanisms remain unclear. Here we suggested that transmembrane BAX inhibitor motif-containing 1 (Tmbim1) is down-regulated in the hearts of mice fed with high fat diet (HFD). We provided evidence that Tmbim1 knockout (KO) accelerated HFD-induced metabolic disorders in mice, as supported by the remarkable increase of fasting serum glucose and insulin levels. HFD-induced cardiac dysfunctions were greatly intensified by the loss of Tmbim1, along with higher levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in serum. In addition, Tmbim1 deletion significantly enhanced lipid accumulation in heart of mice administrated with HFD. Furthermore, Tmbim1 knockout reinforced myocardial inflammation, evidenced by increasing the expression of pro-inflammatory cytokines (interleukin 1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α)), and the activation of nuclear factor-κB (NF-κB) signaling pathway. Tmbim1 deficiency strengthened oxidative damage in hearts of HFD-fed mice, accompanied with a significant reduction of nuclear factor-erythroid 2 related factor 2 (Nrf-2) pathway. In palmitate (PA)-treated primary cardiomyocytes, Tmbim1 ablation markedly enhanced cell inflammation and oxidative stress, which were abolished by the suppression of ROS generation and NF-κB activation. Taken together, these findings suggested that Tmbim1 might be a key suppressor of metabolic stress-induced cardiomyopathy, which could be a promising target for the treatment of metabolic syndrome-triggered myocardial damage and heart failure.

Therapeutic Effect of External Application of Ligustrazine Combined with Holistic Nursing on Pressure Sores.

BACKGROUND This study aimed to explore the therapeutic effect of external application of ligustrazine combined with holistic nursing on pressure sores, as well as the underlying mechanism. MATERIAL AND METHODS From February 2014 to March 2015, a total of 32 patients with Phase II and Phase III pressure sores were enrolled and randomly assigned to an experimental group or a control group. The clinical data were comparable between the 2 groups. In addition to holistic nursing, the patients in the experimental group received 4 weeks of continuous external application of ligustrazine, whereas patients in the control group received compound clotrimazole cream. Therapeutic effect and healing time were recorded. HaCaT cells were used as an in vitro model for mechanism analysis of the effect of ligustrazine in treating pressure sores. After culturing with different concentrations of ligustrazine or the inhibitor of AKT (LY294002) for 72 h, cell viability, clone formation numbers, and levels of phosphatidyl inositol 3-kinase (PI3K), p-AKT, and p-mammalian target of rapamycin (mTOR) were determined. RESULTS Compared to the control group, the total effective rate in the experimental group was significantly higher, and the healing time was significantly reduced. Cell viability and clone formation numbers were significantly upregulated by ligustrazine in a dose-dependent manner. Both the cell viability and clone formation numbers were significantly inhibited by application of LY294002. CONCLUSIONS Our results suggest that ligustrazine combined with holistic nursing is an effective treatment of pressure sores. The protective effect may be associated with the promotion of cell growth by activation of the PI3K/AKT pathway.

Clinical effects of Angelica dahurica dressing on patients with I-II phase pressure sores.

OBJECTIVE: Angelica dahurica is a well-known traditional Chinese Medicine (TCM), while little information is available about its effects on pressure sores. We aimed to investigate the clinical effect of Angelica dahurica on patients with I-II phase pressure sores, as well as the underlying mechanism. METHODS: Patients (n = 98) with phase I and phase II pressure sores were enrolled and randomly assigned to control and treated groups. In addition to holistic nursing, patients in the control group received compound clotrimazole cream, while patients in the treated group received continuous 4 weeks of external application of Angelica dahurica dressing. Therapeutic effect was recorded, along with the levels of interleukin-8 (IL-8), epidermal growth factor (EGF), transforming growth factor (TGF)-ß, and vascular endothelial growth factor (VEGF). Besides, HaCaT cells were cultured with different concentrations of Angelica dahurica, and then cell viability, clone formation numbers, cell cycle, and levels of cyclin D1 and cyclin-dependent kinase (CDK) 2 were determined. RESULTS: The total effective rate in the treated group was significantly higher than in the control group. Levels of IL-8, EGF, TGF-ß, and VEGF were statistically increased by Angelica dahurica. In addition, the cell viability and clone formation numbers were significantly upregulated by Angelica dahurica in a dose-dependent manner. Also, the percentage of cells in G0/G1 phase, and levels of cyclin D1 and CDK2 were significantly elevated. CONCLUSION: Our results suggest that Angelica dahurica may provide an effective clinical treatment for I-II phase pressure sores.

Nocardioides soli sp. nov., a carbendazim-degrading bacterium isolated from soil under the long-term application of carbendazim.

The taxonomic status of a carbendazim-degrading strain, mbc-2(T), isolated from soil under the long-term application of carbendazim in China was determined by means of a polyphasic study. The cells were Gram-stain-positive, motile and rod-shaped. Strain mbc-2(T) grew optimally at pH 7.0, 30-35 °C and in the presence of 1% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain mbc-2(T) fell within the genus Nocardioides, forming a coherent cluster with the type strain of Nocardioides hankookensis, with which it exhibited 16S rRNA gene sequence similarity values of 97.9%. The chemotaxonomic properties of strain mbc-2(T) were consistent with those of the genus Nocardioides: the cell-wall peptidoglycan type was based on ll-2,6-diaminopimelic acid, the predominant menaquinone was MK-8 (H4) and the major fatty acid was iso-C(16 : 0). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, unknown phospholipids and an unknown aminolipid. The DNA G+C content was 72 mol%. Strain mbc-2(T) exhibited DNA-DNA relatedness values of 12.5±1.5%, 23.7±2.7% and 26.3±3.2% with respect to Nocardioides hankookensis DS-30(T), Nocardioides aquiterrae GW-9(T) and Nocardioides pyridinolyticus OS4(T). On the basis of the data obtained, strain mbc-2(T) represents a novel species of the genus Nocardioides, for which the name Nocardioides soli sp. nov. is proposed. The type strain is mbc-2(T) ( = KACC 17152(T) = CCTCC AB 2012934(T)).