Preoperative prediction of macrotrabecular-massive hepatocellular carcinoma through dynamic contrast-enhanced magnetic resonance imaging-based radiomics.

BACKGROUND: Macrotrabecular-massive hepatocellular carcinoma (MTM-HCC) is closely related to aggressive phenotype, gene mutation, carcinogenic pathway, and immunohistochemical markers and is a strong independent predictor of early recurrence and poor prognosis. With the development of imaging technology, successful applications of contrast-enhanced magnetic resonance imaging (MRI) have been reported in identifying the MTM-HCC subtype. Radiomics, as an objective and beneficial method for tumour evaluation, is used to convert medical images into high-throughput quantification features that greatly push the development of precision medicine. AIM: To establish and verify a nomogram for preoperatively identifying MTM-HCC by comparing different machine learning algorithms. METHODS: This retrospective study enrolled 232 (training set, 162; test set, 70) hepatocellular carcinoma patients from April 2018 to September 2021. A total of 3111 radiomics features were extracted from dynamic contrast-enhanced MRI, followed by dimension reduction of these features. Logistic regression (LR), K-nearest neighbour (KNN), Bayes, Tree, and support vector machine (SVM) algorithms were used to select the best radiomics signature. We used the relative standard deviation (RSD) and bootstrap methods to quantify the stability of these five algorithms. The algorithm with the lowest RSD represented the best stability, and it was used to construct the best radiomics model. Multivariable logistic analysis was used to select the useful clinical and radiological features, and different predictive models were established. Finally, the predictive performances of the different models were assessed by evaluating the area under the curve (AUC). RESULTS: The RSD values based on LR, KNN, Bayes, Tree, and SVM were 3.8%, 8.6%, 4.3%, 17.7%, and 17.4%, respectively. Therefore, the LR machine learning algorithm was selected to construct the best radiomics signature, which performed well with AUCs of 0.766 and 0.739 in the training and test sets, respectively. In the multivariable analysis, age [odds ratio (OR) = 0.956, P = 0.034], alpha-fetoprotein (OR = 10.066, P < 0.001), tumour size (OR = 3.316, P = 0.002), tumour-to-liver apparent diffusion coefficient (ADC) ratio (OR = 0.156, P = 0.037), and radiomics score (OR = 2.923, P < 0.001) were independent predictors of MTM-HCC. Among the different models, the predictive performances of the clinical-radiomics model and radiological-radiomics model were significantly improved compared to those of the clinical model (AUCs: 0.888 vs 0.836, P = 0.046) and radiological model (AUCs: 0.796 vs 0.688, P = 0.012), respectively, in the training set, highlighting the improved predictive performance of radiomics. The nomogram performed best, with AUCs of 0.896 and 0.805 in the training and test sets, respectively. CONCLUSION: The nomogram containing radiomics, age, alpha-fetoprotein, tumour size, and tumour-to-liver ADC ratio revealed excellent predictive ability in preoperatively identifying the MTM-HCC subtype.

A new sesquiterpene synthase catalyzing the formation of (R)-ß-bisabolene from medicinal plant Colquhounia coccinea var. mollis and its anti-adipogenic and antibacterial activities.

The sesquiterpene ß-bisabolene possessing R and S configurations is commonly found in plant essential oils with antimicrobial and antioxidant activities. Here, we report the cloning and functional characterization of a (R)-ß-bisabolene synthase gene (CcTPS2) from a Lamiaceae medicinal plant Colquhounia coccinea var. mollis. The biochemical function of CcTPS2 catalyzing the cyclization of farnesyl diphosphate to form a single product (R)-ß-bisabolene was characterized through an engineered Escherichia coli producing diverse polyprenyl diphosphate precursors and in vitro enzyme assay, indicating that CcTPS2 was a high-fidelity (R)-ß-bisabolene synthase. The production of (R)-ß-bisabolene in an engineered E. coli strain harboring the exogenous mevalonate pathway, farnesyl diphosphate synthase and CcTPS1 genes was 17 mg/L under shaking flask conditions. Ultimately, 120 mg of purified (R)-ß-bisabolene was obtained from the engineered E. coli, and its structure was elucidated by detailed spectroscopic analyses (including 1D and 2D NMR, and specific rotation). Four chimeric enzymes were constructed through domain swapping, which altered the product outcome, indicating the region important for substrate and product specificity. In addition, (R)-ß-bisabolene exhibited anti-adipogenic activity in the model organism Caenorhabditis elegans and antibacterial activity selectively against Gram-positive bacteria.

Performance of contrast-enhanced ultrasound for lymph node metastasis in papillary thyroid carcinoma: a meta-analysis.

Background: Papillary thyroid carcinoma is the most common thyroid carcinoma worldwide. Papillary thyroid carcinoma metastasis to the cervical region increases the probability of local or regional recurrence and the requirement for further surgery. Contrast-enhanced ultrasound has been suggested as a possible adjunct diagnostic technique for evaluating papillary thyroid carcinoma metastatic lymph nodes in several studies. This meta-analysis aims to evaluate the diagnostic accuracy of contrast-enhanced ultrasound for cervical lymph nodes metastatic in papillary thyroid carcinoma patients. Methods: A search for studies evaluating the role of contrast-enhanced ultrasound for assessing cervical lymph nodes metastatic in papillary thyroid carcinoma patients from January 2000 to May 2022 was performed in PubMed, Embase, OVID, and Web of Science databases. The Quality Assessment of Diagnostic Accuracy Studies 2 evaluated the quality of the studies. All analyses were performed using Review Manager 5.3 and Stata 17.0. Results: A total of seven articles were finally included in this study. Perfusion type, enhancement homogeneous, hilum absent, and perfusion defect were involved in the meta-analysis as the standard of contrast-enhanced ultrasound, among which, perfusion type showed the best diagnostic performance. The pooled estimated sensitivity, specificity, positive likelihood, negative likelihood ratio, and diagnostic odds ratio of perfusion type in contrast-enhanced ultrasound for detecting lymph node metastasis were 0.95 (0.91, 0.97), 0.87 (0.69, 0.96), 7.51 (2.80, 20.14), 0.06 (0.03, 0.10), and 124.17 (42.78, 360.46), respectively. Heterogeneity was moderate. Conclusion: The perfusion type in contrast-enhanced ultrasound has good diagnostic performance for cervical lymph nodes metastasis in papillary thyroid carcinoma patients.

Characterization of myogenic regulatory factors, myod and myf5 from Megalobrama amblycephala and the effect of lipopolysaccharide on satellite cells in skeletal muscle.

Myod and Myf5 are muscle-specific basic helix-loop-helix (bHLH) transcription factors that play essential roles in regulating skeletal muscle development and growth. In order to investigate potential function of myod and myf5 of Megalobrama amblycephala, an economically important freshwater fish species, in the present study, we characterized the sequences and expression profiles of M. amblycephala myod and myf5. The open reading frame (ORF) sequences of myod and myf5 encoded 275 and 240 amino acids, respectively, possessing analogous structure with the highly conserved domains, bHLH and C-terminal helix III domains. Spatio-temporal expression patterns revealed that myod and myf5 were predominant in skeletal muscle with the highest expression in white muscle, and the highest at 10 days post-hatching (dph) and the segmentation period, respectively. Furthermore, we evaluated the effects of lipopolysaccharide (LPS) on the expression of muscle-related genes in white and red muscle, and proliferation and differentiation of satellite cells. The myod, myf5 and pax-7 expression generally increased and then decreased with increase of LPS concentration and treatment time in red muscle, while these genes showed inconsistent expression patterns in white muscle. In addition, LPS administration caused the frequency increase of satellite cells in red and white muscle especially at 3 and 7 days after LPS-injection.

The Novel Function of Unsymmetrical Chiral CCN Pincer Nickel Complexes as Chemotherapeutic Agents Targeting Prostate Cancer Cells.

We report that the pincer nickel complexes display prostate cancer antitumor properties through inhibition of cell proliferation. Notably, they display better antitumor properties than cisplatin. Mechanistic studies reveal that these pincer nickel complexes trigger cell apoptosis, most likely due to cell cycle arrest. Interestingly, these complexes also inhibit androgen receptor (AR) and prostate-specific antigen (PSA) signaling, which are critical for prostate cancer survival and progression. Our study reveals a novel function of pincer nickel complexes as potential therapeutic drugs in prostate cancer.

Comparison of effects of dsRNA and siRNA RNA interference on insulin-like androgenic gland gene (IAG) in red swamp crayfish Procambarus clarkii.

RNA interference (RNAi), which employs double-strand RNA (dsRNA) or small interference RNA (siRNA), is a popular reverse genetic manipulation tool to study gene function. Presently, there is few reports on the implementation of RNAi on the insulin-like androgenic gland gene (IAG) in red swamp crayfish Procambarus clarkii. In this study, the effective sequence of siRNA and optimal injection dose were determined, and the effects of RNAi using dsRNA, siRNA, and long-term RNAi were investigated. The results showed that the doses of 0.5 and 1 µg/g of body weight of IAG-siRNA3 produced significantly better inhibition than 0.1 µg/g. qPCR assays showed that both dsRNA and siRNA silenced the IAG expression in five tissues (brain, ventral nerve cord, androgenic gland, testis, and vas deferens) in adult P. clarkii, with the effectiveness decreasing over time, inhibiting the production of spermatid. dsRNA exhibited a longer interference effect than siRNA in adults. For long-term interference (P. clarkii juveniles were injected 7 times with 1 µg/g of body weight of IAG-dsRNA), and found that the secondary sexual characteristics of juveniles were affected, while the control group developed normally. The results of this study could lay the foundation for crayfish sex reversal with IAG RNAi, and provide the reference for those studies in which the technique of RNAi was used.

Bioinformatic identification of key candidate genes and pathways in axon regeneration after spinal cord injury in zebrafish.

Zebrafish and human genomes are highly homologous; however, despite this genomic similarity, adult zebrafish can achieve neuronal proliferation, regeneration and functional restoration within 6-8 weeks after spinal cord injury, whereas humans cannot. To analyze differentially expressed zebrafish genes between axon-regenerated neurons and axon-non-regenerated neurons after spinal cord injury, and to explore the key genes and pathways of axonal regeneration after spinal cord injury, microarray GSE56842 was analyzed using the online tool, GEO2R, in the Gene Expression Omnibus database. Gene ontology and protein-protein interaction networks were used to analyze the identified differentially expressed genes. Finally, we screened for genes and pathways that may play a role in spinal cord injury repair in zebrafish and mammals. A total of 636 differentially expressed genes were obtained, including 255 up-regulated and 381 down-regulated differentially expressed genes in axon-regenerated neurons. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were also obtained. A protein-protein interaction network contained 480 node genes and 1976 node connections. We also obtained the 10 hub genes with the highest correlation and the two modules with the highest score. The results showed that spectrin may promote axonal regeneration after spinal cord injury in zebrafish. Transforming growth factor beta signaling may inhibit repair after spinal cord injury in zebrafish. Focal adhesion or tight junctions may play an important role in the migration and proliferation of some cells, such as Schwann cells or neural progenitor cells, after spinal cord injury in zebrafish. Bioinformatic analysis identified key candidate genes and pathways in axonal regeneration after spinal cord injury in zebrafish, providing targets for treatment of spinal cord injury in mammals.

[Protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride-induced liver fibrosis in rats].

This experiment was aimed to discuss the protective effect and mechanism of total lignans from Tibetan medicinal Herpetospermum seeds on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. Forty-eight male Sprague-Dawley rats were randomly divided into the blank control group (G1), model group (G2), total lignans high, middle and low dose groups (400,200, and 100 mg•kg⁻¹â€¢d⁻¹)(G3/4/5) and the glycyrrhizin positive control group (25 mg•kg⁻¹â€¢d⁻¹)(G6), n=8 in each group. The rats in blank group received normal feeding; the rats in model group, total lignans low, middle and high dose groups and glycyrrhizic group were subcutaneously in jected with 3 mL•kg⁻¹ olive oilsolution containing 40%CCl4 every two or three days for Eight weeks. During the course, the rats inblank group and model group were orally administered with 2 mL normal saline, and the rats in total lignans groups and the glycyrrhizin positive control group received corresponding doses of drugs by intragastric administration. Eight weeks later, after the the last time modeling, the rats were sacrificed. Then the biochemical analysis was used to determine alanine aminotransferase(ALT), aspartate aminotransferase(AST), and alkaline phosphatase (ALP) levels in serum while enzyme-linked immuno sorbent assay(ELISA) was applied for detecting transforming growth factor ß1(TGF-ß1), hyaluronic acid(HA), hydroxy-proline(HYP) and superoxide dismutase(SOD) levels in serum. HE and Masson's trichrome stainings were conducted in liver tissues to observe the pathological variations and grades of hepatic fibrosis. The results showed that as compared with the model group, the levels of ALT, AST, ALP, TGF-ß1, HA, HYP and SOD in serum of total lignans groups were significantly decreased (P<0.05, P<0.01); levels of SOD in the liver tissue homogenate were increased(P<0.05, P<0.01); the pathological damage of the liver tissues were relieved (P<0.05, P<0.01), and liver fibrosis scores were decreased(P<0.05, P<0.01). The above experimentsindicated that total lignans from Tibetan medicinal Herpetospermum seeds can effectively reduce carbon tetrachloride-induced hepatic injury of rat liver fibrosis, reduce the degree of liver fibrosis, and its mechanism maybe associated with down-regulating TGF-ß1 expression.

[Analysis of Atmospheric Particulate Matter Pollution Characteristics by LIDAR in Beijing During Spring Festival, 2016].

Real-time aerosol extinction retrieved by Micro-pulse LIDAR and concentrations of PM2.5 and PM10 in Beijing were analyzed to investigate the air quality during the Spring Festival. The results showed that fireworks on the New Year's Eve resulted in a sharp increase in particulate matter concentrations in a short time. The maximum concentration of PM2.5 at Guanyuan station was 639.3 µg·m-3, which increased by nearly 30 times in 9 h. The maximum hourly concentration of particulate matter at Dingling and Liulihe suburban stations were significantly higher than that in Guanyuan station, the maximum values were more than 1000 µg·m-3. The particulate matter levels were continuously high on February 10-12 and the concentration of particulate matter at Dingling and Liulihe suburban stations were higher than that at Guanyuan. LIDAR results showed no obvious changes in the extinction coefficient at Dingling on the New Year's Eve. The extinction coefficient at Liulihe was greater than 1 km-1, but the particulate matter pollution was concentrated at altitudes less than 400 m. The extinction coefficient at Chegongzhuang was still higher than 0.4 km-1 at 500 m; however, the duration of pollution was shorter than that of Liulihe. The extinction coefficients at 105 m at all three stations during the New Year's Eve were significantly higher than those at 405 m. There were significant differences in the vertical extinction characteristics of the three sites. The background maximum values of Dingling, Chegongzhuang, and Liulihe were 0.09 km-1, 0.20 km-1, and 0.19 km-1 under 1.0 km, respectively. The maximum extinction coefficients at 00:00 (midnight) were 0.23 km-1, 1.36 km-1, and 1.19 km-1, which were 2.6 times, 6.8 times, and 6.0 times higher than the background value at the same time, respectively. In summary, discharge of fireworks led to a dramatic increase in the extinction coefficient of particulate matter. Temperature inversion and lower wind speeds were the main meteorological factors that contributed to this pollution event.

Protective Effects of MDG-1, a Polysaccharide from Ophiopogon japonicus on Diabetic Nephropathy in Diabetic KKAy Mice.

Ophiopogon japonicus is a traditional Chinese medicine that might be effective for treating type 2 diabetes. Recent research confirmed that MDG-1, a polysaccharide from O. japonicas, activates the PI3K/Akt signaling pathway and improves insulin sensitivity in a diabetic KKAy mouse model, but little is known about its effects on diabetic nephropathy. In this study, KKAy mice were orally administered distilled water (control group), MDG-1, or rosiglitazone for 12 weeks. Blood glucose levels were tested every two weeks for the fed mice. At 6 and 12 weeks, blood samples were collected for biochemical examination. At the end of the experiment, all kidney tissues were collected for histological examination and western blot analysis. Results show that MDG-1 (300 mg/kg) significantly decreased the levels of blood glucose, triglycerides, blood urine nitrogen and albumin, and significantly inhibited the expression of transforming growth factor-beta 1 and connective tissue growth factor. Moreover, MDG-1 could alleviate glomerular mesangial expansion and tubulointerstitial fibrosis in the diabetic mice, as confirmed by histopathological examination. These data indicated that MDG-1 ameliorates renal disease in diabetic mice by reducing hyperglycemia, hyperinsulinemia, and hyperlipidemia, and by inhibiting intracellular signaling pathways.

MDG-1, an Ophiopogon polysaccharide, regulate gut microbiota in high-fat diet-induced obese C57BL/6 mice.

Most plant polysaccharides cannot be digested and utilized by host enzymes, and must be subjected to microbial fermentation before being assimilated by the host. MDG-1, a water-soluble ß-d-fructan extracted from the roots of Ophiopogon japonicus, has potent anti-obesity and hypoglycemic effects. Interestingly, we found that MDG-1 is hardly absorbed into the blood. We presumed that MDG-1 might exhibit its potent efficacy via regulating the gut microbiota of the host. However, the overall microbiota structure variation of obese mice treated with MDG-1 and the direct metabolic consequences of MDG-1 on specific microbiota phyla remain poorly understood. Here, obese male C57BL/6 mice induced by a high-fat diet were given either vehicle or MDG-1 at a dose of 300mg/kg for 12 weeks and the overall fecal gut microbiota structure change was analyzed via pyrosequencing. On this basis, we further separated and identified the dominant bacteria of the feces from the MDG-1 treated mice. These bacteria were then cultured with MDG-1 in vitro and their metabolic profiles were analyzed via a metabonomic approach. The results showed that MDG-1 could decrease the ratio of Firmicutes/Bacteroidetes, adjust the abnormal gut microbiota to the normal state and alter their metabolic profiles. In addition, we identified that the indigestible MDG-1 could be degraded and utilized by gut microbiota that could, in turn, be assimilated and used by the host, where it exerted weight loss effects, energy metabolism promotion and boosted the immune system effectiveness.

[Effect of MDG-1, a polysaccharide from Ophiopogon japonicas, on diversity of lactobacillus in diet-induced obese mice].

For understanding the effect of MDG-1, a water-soluble ß-D-fructan polysaccharide from Ophiopogon japonicas, on intestinal microecological balance, especially on the changes of lactobacillus, sixty 8-week-old male C57BL/6J mice were given a high-fat diet for six weeks and were also gavaged with saline once a day simultaneously. Then the mice which is below 30 grams or dropped more than 10% through lavage were eliminated and the rest were randomly divided into four groups: diet-induced obese (DIO) model group (n = 12, gavaged with saline), low-dose MDG-1 group (n = 12, gavaged with MDG-1, 75 mg · kg(-1)) , medial-dose MDG- 1 group (n = 12, gavaged with 150 mg · kg(-1)), and high-dose MDG-1 group (n = 12, gavaged with 300 mg · kg(-1)) according to the weight and blood glucose; the model group and MDG-1 group were placed on a high-fat diet while the normal control group (n = 12, gavaged with saline) were kept on a low-fat diet through the experiment. After 12-weeks of treatment, feces samples were collected and cultured for intestinal microecological balance analysis. Then the intestinal probiotics were cultured through traditional methods combined with modified gradient gel electrophoresis (DGGE) method. The changes of lactobacillus in each treatment group were also detected by a statistical analysis of the total number of the intestinal flora. We have established the phylogenetic tree by 16S rDNA sequencing and use some molecular identification methods such as PCR-DGGE to analyse the changes of the dominant bacteria floras, and also get the pure culture. In conclusion, different concentrations of MDG-1 can increase the number of the intestinal probiotics, especially Taiwan lactobacillus and Lactobacillus murinus, and improve their diversity and promote proliferation in a dose-dependent way.

[Observation on therapeutic effect of blood-letting puncture combined with red-hot needle therapy on knee osteoarthritis].

OBJECTIVE: To observe the therapeutic effect of blood-letting puncture combined with red-hot needle therapy on knee osteoarthritis. METHODS: One hundred and twenty-nine cases were randomly divided into a bloodletting puncture plus red-hot needle therapy group (n=73) and a routine acupuncture group (n=56). The blood letting puncture plus red-hot needle therapy group were treated by blood-letting puncture at Weizhong (BL 40), and red-hot needle pricking Heding (EX-LE 2), Dubi (ST 35), Xiyan (EX-LE 5), Yinlingquan (SP 9), Yanglingquan (GB 34), Xuanzhong (GB 39) and Ashi points, twice each week, 4 times constituting one course. The routine acupuncture group were treated by routine acupuncture at the same points as those for red-hot needle pricking, once each day, two weeks constituting one course. RESULTS: After treatment for 2 courses, the joint pain score and the illness serious index were 2.68+/-0.88 and 4.25+/-1.02, and 4.68+/-1.89 and 7.46+/-2. 13 in the two groups, respectively, with very significant differences before and after treatment in the two groups (P<0.01), the former being better than the later (P<0.05). The clinical cured rate and the total effective rate were 37.0% and 94.5% in the blood-letting puncture plus red-hot needle therapy group and 19.6% and 89.3% in the routine acupuncture group, with a very significant difference between the two groups(P<0. 01). CONCLUSION: Blood-letting puncture combined with red-hot needle therapy has obvious therapeutic effect on knee osteoarthritis.