Real-world evidence of avatrombopag for the treatment of immune thrombocytopenia intolerant or ineffective to eltrombopag/hetrombopag.

Due to the limited real-world research on the application of avatrombopag (AVA) for immune thrombocytopenia (ITP) in China, we evaluated the effectiveness and safety of AVA in clinical practice. We included 121 adult ITP patients treated with AVA across three medical centres. Based on the reasons for choosing AVA, these patients were divided into eltrombopag (ELT)/hetrombopag (HET) intolerance group (IG), and ELT/HET unresponsive group (UG). Compared with UG, more patients in IG had a history of liver disease and received fewer treatments before AVA. Amongst all patients, 83% had platelet response (≥30 × 109/L) after AVA and 62% achieved complete response (≥100 × 109/L, CR). Sixty-two percent in IG and 56% in UG were able to discontinue more than one concomitant ITP medication. A total of 17 patients underwent multiple switches of thrombopoietin receptor agonists (TPO-RAs), resulting in an 88% platelet response rate. Sixty-three patients discontinued AVA, 27% were due to unaffordability. AVA was well tolerated in most patients. In the ITP population, AVA proved effective and safe, particularly in patients intolerant or unresponsive to ELT/HET. Patients benefited from TPO-RAs switches, particularly those undergoing multiple switches. However, many patients struggled with the long-term financial burden of AVA.

Discrimination between benign and malignant gallbladder lesions on enhanced CT imaging using radiomics.

BACKGROUND: Gallbladder cancer is a rare but aggressive malignancy that is often diagnosed at an advanced stage and is associated with poor outcomes. PURPOSE: To develop a radiomics model to discriminate between benign and malignant gallbladder lesions using enhanced computed tomography (CT) imaging. MATERIAL AND METHODS: All patients had a preoperative contrast-enhanced CT scan, which was independently analyzed by two radiologists. Regions of interest were manually delineated on portal venous phase images, and radiomics features were extracted. Feature selection was performed using mRMR and LASSO methods. The patients were randomly divided into training and test groups at a ratio of 7:3. Clinical and radiomics parameters were identified in the training group, three models were constructed, and the models' prediction accuracy and ability were evaluated using AUC and calibration curves. RESULTS: In the training group, the AUCs of the clinical model and radiomics model were 0.914 and 0.968, and that of the nomogram model was 0.980, respectively. There were statistically significant differences in diagnostic accuracy between nomograms and radiomics features (P <0.05). There was no significant difference in diagnostic accuracy between the nomograms and clinical features (P >0.05) or between the clinical features and radiomics features (P >0.05). In the testing group, the AUC of the clinical model and radiomics model were 0.904 and 0.941, and that of the nomogram model was 0.948, respectively. There was no significant difference in diagnostic accuracy between the three groups (P >0.05). CONCLUSION: It was suggested that radiomics analysis using enhanced CT imaging can effectively discriminate between benign and malignant gallbladder lesions.

A novel AGK splicing mutation in a patient with Sengers syndrome and left ventricular non-compaction cardiomyopathy.

BACKGROUND: Sengers syndrome characterized by hypertrophic cardiomyopathy is an extremely rare genetic disorder. Sengers syndrome associated with left ventricular non-compaction (LVNC) has not been described. METHODS: Genetic testing was used to identify candidate AGK variants in the proband. The predicted molecular structures were constructed by protein modeling. Exon skipping caused by the identified splicing mutations was verified by in silico analyses and in vitro assays. The genotypic and phenotypic features of patients with AGK splicing mutations were extracted by a systematic review. RESULTS: The proband was characterized by Sengers syndrome and LVNC and caused by a novel compound heterozygous AGK splicing mutation. This compound mutation simultaneously perturbed the protein sequences and spatial conformation of the acylglycerol kinase protein. In silico and in vitro analyses demonstrated skipping of exons 7 and 8 and premature truncation as a result of exon 8 skipping. The systematic review indicated that patients with an AGK splicing mutation may have milder phenotypes of Sengers syndrome. CONCLUSIONS: The genotypic and phenotypic spectrums of Sengers syndrome have been expanded, which will provide essential information for genetic counseling. The molecular mechanism in AGK mutations can offer insights into the potential targets for treatment. IMPACT: First description of a child with Sengers syndrome and left ventricular non-compaction cardiomyopathy. A novel pathogenic compound heterozygous splicing mutation in AGK for Sengers syndrome was identified. The identified mutations led to exons skipping by in silico analyses and in vitro assays.

Effect of different application duration of a venous foot pump on prevention of venous thromboembolism after hip and knee arthroplasty: a multicenter prospective clinical trial.

OBJECTIVE: To investigate the optimal duration of applying a venous foot pump (VFP) in the prevention of venous thromboembolism (VTE) following hip and knee arthroplasty. METHODS: A total of 230 patients undergoing hip and knee arthroplasty between March 2021 and March 2022 in orthopaedic departments of four major teaching hospitals were prospectively enrolled. Patients were randomly divided into five groups based on the duration of the VFP application. Postoperative deep vein thromboses (DVT), including proximal, distal, and intermuscular DVT, were recorded for analysis. Postoperative blood coagulation examinations, such as D-dimer and active partial thromboplastin time (APTT), pain outcome, and degree of comfort were also collected. RESULTS: Two of the 230 patients withdrew due to early discharge from the hospital, and 228 patients were included in the final analysis. The mean age was 60.38 ± 13.33 years. The baseline characteristics were comparable among the five groups. Compared with the other groups, patients treated with 6-hour VFP had the lowest incidence of DVT (8.7%, 4/46), followed by those treated with 1-hour VFP (15.2%, 7/46), 12-hour VFP (15.6%, 7/45), 18-hour VFP(17.8%, 8/45) and 20-hour VFP(21.7%, 10/46), but with no significant difference (P = 0.539). Regarding postoperative blood coagulation examinations, patients treated with 6-hour VFP had the lowest D-dimer (P = 0.658) and the highest APTT (P = 0.262) compared with the other four groups. 6-hour VFP also had the lowest pain score (P = 0.206) and the highest comfort score (P = 0.288) compared with the other four groups. CONCLUSIONS: Six hours may be the optimal duration of applying VFP for the prevention of VTE in patients undergoing hip and knee arthroplasty in terms of VTE incidence, postoperative blood coagulation examinations, pain outcomes, and comfort scores.

Swamp eel aldehyde reductase is involved in response to nitrosative stress via regulating NO/GSH levels.

Aldehyde reductase (ALR) plays key roles in the detoxification of toxic aldehyde. In this study, the authors cloned the swamp eel ALR gene using rapid amplification of cDNA ends-PCR (RACE-PCR). The recombinant protein (rALR) was expressed in Escherichia coli and purified using a Ni2+ -NTA chelating column. The rALR protein exhibited efficient reductive activity towards several aldehydes, ketones and S-nitrosoglutathione (GSNO). A spot assay suggested that the recombinant E. coli strain expressing rALR showed better resistance to formaldehyde, sodium nitrite and GSNO stress, suggesting that swamp eel ALR is crucial for redox homeostasis in vivo. Consequently, the authors investigated the effect of rALR on the oxidative parameters of the liver in swamp eels challenged with Aeromonas hydrophila. The hepatic glutathione (GSH) content significantly increased, and the hepatic NO content and levels of reactive oxygen species and reactive nitrogen species significantly decreased when rALR was administered. In addition, the mRNA expression of hepatic Alr, HO1 and Nrf2 was significantly upregulated, whereas the expression levels of NF-κB, IL-1ß and NOS1 were significantly downregulated in the rALR-administered group. Collectively, these results suggest that ALR is involved in the response to nitrosative stress by regulating GSH/NO levels in the swamp eel.

Evaluation of Radiomics Models Based on Computed Tomography for Distinguishing Between Benign and Malignant Thyroid Nodules.

AIM: The aim of the study was to investigate the diagnostic value of radiomics models based on computed tomography (CT) in distinguishing between benign and malignant thyroid nodules. MATERIALS AND METHODS: We conducted a retrospective analysis of the clinical and imaging data of 172 patients with pathology-confirmed thyroid nodules (83 benign nodules and 89 malignant nodules). All patients underwent a plain CT scan + arterial and venous contrast enhancement before the operation. Using the stratified random sampling method, patients were divided into a training group (121 cases) and a test group (51 cases) at a ratio of 7:3. A.K. software was used to extract radiomics features from the preoperative CT images, and minimum redundancy maximum relevance and least absolute shrinkage and selection operator regression analyses were then used for feature screening and model construction. Receiver operating characteristic (ROC) curves were constructed for the training and test groups to verify model performance and evaluate the efficacy of the radiomics features in identifying benign and malignant thyroid nodules. We then used the most efficient models to construct a nomogram. For the training group, 1-way analysis of variance and multivariate logistic regression analysis were used to screen statistically significant clinical features, and the radiomics scores were combined to construct a radiomics nomogram. We used ROC curve analysis to evaluate the predictive performance of the model. RESULTS: Screening yielded 21 radiomics features that were used to construct a model for differentiating between benign and malignant thyroid nodules. For the training group, the area under the ROC curve of the prediction models for the noncontrast, arterial phase, and venous phase scans were 0.86 (95% confidence interval [CI], 0.79-0.92), 0.89 (95% CI, 0.83-0.95), and 0.88 (95% CI, 0.82-0.94), respectively, and the corresponding diagnostic accuracy was 0.78, 0.84, and 0.83. For the test group, the corresponding 3-phase under the ROC curves for the test group were 0.76 (95% CI, 0.63-0.90), 0.78 (95% CI, 0.65-0.91), and 0.76 (95% CI, 0.62-0.90), and the corresponding accuracy was 0.63, 0.77, and 0.75. Thus, the arterial phase model exhibited the best diagnostic performance. The multivariate logistic regression results showed that morphology regularity and the cystic degeneration ratio were independent clinical risk factors for predicting benign and malignant thyroid nodules. The arterial phase radiomics score and clinically independent factors were then used to construct a nomogram. The nomogram had good discriminability for the training group (0.93; 95% CI, 0.88-0.98) and the test group (0.84; 95% CI, 0.73-0.95), achieving significantly higher accuracies than the radiomics score and clinical characteristics alone. CONCLUSIONS: The radiomics nomogram constructed by combining radiomics characteristics and clinical risk factors was efficacious for distinguishing benign and malignant thyroid nodules.

The effect of talus osteochondral defects of different area size on ankle joint stability: a finite element analysis.

BACKGROUND: Osteochondral lesion of the talus (OLT) is one of the most common ankle injuries, which will lead to biomechanical changes in the ankle joint and ultimately affect ankle function. Finite element analysis (FEA) is used to clarify the effect of talus osteochondral defects on the stability of the ankle joint at different depths. However, no research has been conducted on talus osteochondral defect areas that require prompt intervention. In this research, FEA was used to simulate the effect of the area size of talus osteochondral defect on the stress and stability of the ankle joint under a specific depth defect. METHODS: Different area sizes (normal, 2 mm* 2 mm, 4 mm* 4 mm, 6 mm* 6 mm, 8 mm* 8 mm, 10 mm* 10 mm, and 12 mm* 12 mm) of the three-dimensional finite element model of osteochondral defects were established. The model was used to simulate and calculate joint stress and displacement of the articular surface of the distal tibia and the proximal talus when the ankle joint was in the heel-strike, midstance, and push-off phases. RESULTS: When OLT occurred, the contact pressure of the articular surface, the equivalent stress of the proximal talus, the tibial cartilage, and the talus cartilage did not change significantly with an increase in the size of the osteochondral defect area when the heel-strike phase was below 6 mm * 6 mm. Gradual increases started at 6 mm * 6 mm in the midstance and push-off phases. Maximum changes were reached when the defect area size was 12 mm * 12 mm. The same patterns were observed in the talus displacement. CONCLUSIONS: The effect of the defect area of the ankle talus cartilage on the ankle biomechanics is evident in the midstance and push-off phases. When the size of the defect reaches 6 mm * 6 mm, the most apparent change in the stability of the ankle joint occurs, and the effect does not increase linearly with the increase in the size of the defect.

An fgf21-like gene from swamp eel (Monopterus albus): Recombinant expression and its potential roles in glucose and lipid homeostasis.

Fibroblast growth factor 21 (FGF21) plays important roles in the regulation of glucose and lipid metabolism and energy balance in mammals. In this study, the full-length cDNA of swamp eel fgf21 was cloned. Sequence analysis showed that swamp eel FGF21 displayed high similarity with FGF21 of other vertebrates. Subsequently, a prokaryotic expression vector for swamp eel fgf21 was constructed, and recombinant FGF21 (rFGF21) was successfully induced and purified. To investigate the potential roles of swamp eel FGF21 in glucose and lipid metabolism, we examined the effects of rFGF21 on regulation of glucose and lipid homeostasis in type 1 diabetes mellitus (T1DM) mice as well as swamp eels under glucose stress. In T1DM mice, the levels of blood glucose, serum triglyceride (TG), liver TG, serum total cholesterol (TC), and liver TC were significantly downregulated after repeated daily injection of rFGF21 for 15 days. In addition, liver pathological section analysis indicated that rFGF21 alleviated the degree of damage to liver cells in T1DM mice. Furthermore, rFGF21 significantly upregulated the mRNA expression levels of peroxisome proliferators-activated receptor alpha (Pparα), ß-Klotho, fibroblast growth factor receptor 1 (Fgfr1), phosphoenolpyruvate carboxykinase (Pepck), glucose transporter 1 (Glut1), and glucose transporter 4 (Glut4) in T1DM mouse livers. Moreover, in swamp eels, rFGF21 significantly decreased blood glucose and liver TC levels under glucose stress and upregulated the mRNA expression levels of fgf21, pparα, ß-klotho, and fgfr1 in liver tissue. These results suggested that FGF21 plays important roles in the regulation of glucose and lipid homeostasis in swamp eel.

Characterization, expression, and function analysis of AKR1A1 gene from yellow catfish (Tachysurus fulvidraco).

Aldehyde reductase (AKR1A1) is a carbonyl detoxification protein in toxic aldehyde removal. In the present study, the full-length cDNA of yellow catfish AKR1A1 (TfAKR1A1) was cloned. As expected, yellow catfish AKR1A1 showed similarities with that of other species. Subsequently, prokaryotic expression vector was constructed and recombinant TfAKR1A1 (rTfAKR1A1) was successfully induced and purified. rTfAKR1A1 exhibited reductive activity to many aldehydes and ketones. To determine whether TfAKR1A1 could confer stress tolerance in vitro, the viability of control and TfAKR1A1 expression E. coli under abiotic stress was compared by spot assay. Results showed that the recombinant strain had better stress resistance under cadmium, hydrogen peroxide, and DL-glyceraldehyde stress. Then, effects of an intraperitoneal injection of rTfAKR1A1 protein on cadmium-induced oxidative stress were evaluated. Results displayed that TfAKR1A1 and Nrf2 expression levels were significantly decreased, CAT and SOD expression levels were significantly increased, BCL-2 and IL-10 expression levels were significantly increased, and caspase3a, NF-κB, and IL-1ß expression levels were significantly decreased in protein-injection group. Furthermore, oxidative stress indexes in livers under different protein injection doses were examined by ELISA. Results showed that CAT, SOD, and GSH-Px activities were upregulated, ROS and T-AOC contents were also improved, while MDA content was significantly decreased both in lower and middle dose injection groups. Finally, liver pathological section analysis was performed. Results displayed that liver injury degree in protein-injected groups was lower than that of PBS group under cadmium stress. These results suggested that TfAKR1A1 played important roles in response to cadmium stress in yellow catfish.

AtCPS V326M significantly affect the biosynthesis of gibberellins.

Gibberellins are a class of typical phytohormones, which regulate plant growth and development. The contents of gibberellins dramatically affect the morphology and biomass of plant. The encoding protein of copalyl diphosphate synthase gene (CPS) catalyzes the first-step in the biosynthetic pathway of gibberellins. The mutation in this gene may significantly affect the contents of gibberellins in plants. In this study, we found an EMS-triggered mutant, ga1-168, showing short roots, short hypocotyls, late flowering and dwarf. Map-based cloning revealed that the causal gene of ga1-168 was AtCPS-168, an allele of AtCPS gene. The encoding protein of AtCPS-168 was AtCPS V326M which was resulted from a single-point mutation (guanine to adenine at nucleotide 2768) of AtCPS gene. Protein domain analysis showed that V326 was located in the Terpene_synth domain. The allelism test demonstrated that AtCPS-168 was an allele of AtCPS gene. The transgenic complementation of ga1-168 indicated that AtCPS V326M led to the dwarf and bushy phenotype of ga1-168. The endogenous gibberellins contents analysis suggested that the gibberellins contents of ga1-168 were much lower than that of wild-type. The exogenous GA3 application assay uncovered that application of GA3 can complement the dwarf and bushy phenotype of ga1-168 caused by low endogenous gibberellins contents. Therefore, this study suggested that it is an elegant way to create the ideal plant architecture and height by site-directed mutating the gibberellin biosynthetic genes.

[Health risk assessment of exogenous harmful pollutants in Chinese medicine: a review].

In recent years, the quality and safety problems have been limiting the internationalization of Chinese medicine. The pollutants in Chinese medicine, particularly the exogenous harmful pollutants mainly including mycotoxins, pesticide residues, heavy metals, harmful elements, and sulfur dioxide, are of high risks for people. Therefore, the World Health Organization(WHO) and relevant national organizations have clearly defined the maximum residue limits(MRLs) of such pollutants. Chinese Pharmacopoeia(2020 edition, volume Ⅳ) also demonstrates the detection methods, MRLs and preliminary risk assessment methods for four typical exogenous harmful pollutants in Chinese medicine. Therefore, continuous optimization of the health risk assessment system can further help further raise the quality and safety of Chinese medicine. This paper reviews the research on the health risk assessment of four typical exogenous harmful pollutants in Chinese medicine and discusses the problems of and challenges for the assessment system, which is expected to lay a scientific basis for the establishment of the risk warning mode and response measures suitable for specific types of Chinese medicine.

[Domestic and international research progress of edible and medicinal Arecae Semen].

Arecae Semen, as the first place among "Four South Medicines" in China, has great dual-use value of medicine and food. The research of Arecae Semen was mainly focused on the active ingredients and efficacy value, and its potential safety hazards were also concerned. Until now, there is still a lack of clear boundaries between medicine and food, resulting in its safety cannot be guaranteed. Therefore, it is of great significance to establish clear boundaries of medicine and food use and health risk assessment. In this paper, the differences of pretreatment and application methods of Arecae Semen were analyzed, and the research progress of Arecae Semen in chemical composition identification and toxicology research and safety evaluation were reviewed emphatically. Finally, the differences of quality control and safety evaluation of Arecae Semen in pharmacopoeias or standards were analyzed at home and abroad. It was expected to provide reference value for quality control, safety evaluation and international standardization research of Arecae Semen.

Integrated analysis of immune-related genes in endometrial carcinoma.

BACKGROUND: Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis. METHODS: Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results. RESULTS: A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan-Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells. CONCLUSIONS: Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.

Mimicking Natural Photosynthesis: Solar to Renewable H2 Fuel Synthesis by Z-Scheme Water Splitting Systems.

Visible light-driven water splitting using cheap and robust photocatalysts is one of the most exciting ways to produce clean and renewable energy for future generations. Cutting edge research within the field focuses on so-called "Z-scheme" systems, which are inspired by the photosystem II-photosystem I (PSII/PSI) coupling from natural photosynthesis. A Z-scheme system comprises two photocatalysts and generates two sets of charge carriers, splitting water into its constituent parts, hydrogen and oxygen, at separate locations. This is not only more efficient than using a single photocatalyst, but practically it could also be safer. Researchers within the field are constantly aiming to bring systems toward industrial level efficiencies by maximizing light absorption of the materials, engineering more stable redox couples, and also searching for new hydrogen and oxygen evolution cocatalysts. This review provides an in-depth survey of relevant Z-schemes from past to present, with particular focus on mechanistic breakthroughs, and highlights current state of the art systems which are at the forefront of the field.

Heme oxygenase 1 plays a crucial role in swamp eel response to oxidative stress induced by cadmium exposure or Aeromonas hydrophila infection.

Oxidative stress contributes a lot to initiation and progression of pathological conditions. Heme oxygenase 1 (HO1), a cytoprotective enzyme, is usually upregulated to alleviate oxidative stress in vivo. The function of teleost HO1 in the response to oxidative stress induced by heavy metal exposure and in pathogenic bacterial infection remains uncertain. In the present study, both complementary DNA and genomic sequence of a HO1-like gene cloned from the liver of swamp eel (Monopterus albus) are reported. Sequence analysis showed that the putative amino acid sequence contained a conserved heme oxygenase signature and displayed higher similarity to HO1 genes of other teleosts. Expression profile of swamp eel HO1 was investigated in healthy tissues and in tissues following stimulation with pathogenic bacteria (Aeromonas hydrophila) or cadmium chloride (CdCl2) exposure. Results demonstrated that HO1 messenger RNA (mRNA) was highly expressed in the liver and relatively less in other tissues. Bacterial infection with A. hydrophila significantly changed HO1 mRNA expression in the liver, spleen, and kidney, and the mRNA expression of HO1 and Nrf2 in the liver was elevated after the fish were exposed to CdCl2. Subsequently, the swamp eel HO1 was subcloned into a pET28a expression vector and transformed into Escherichia coli BL21 (DE3). Recombinant HO1 (rHO1) was successfully induced by 0.1 mmol/l IPTG and purified by Ni-NTA His Bind Resin purification system. To determine whether the rHO1 could confer stress tolerance in vitro, the viability of control and HO1-expressing E. coli under CdCl2 stress was compared by spot assay. The rHO1 protein significantly increased survival rates of the bacterial hosts. To evaluate whether intraperitoneal injection with rHO1 protected the liver of swamp eel against A. hydrophila-induced oxidative stress, mRNA expression of HO1, Nrf2, hepcidin, and IL-1ß as well as the oxidative stress-related parameters (ROS and total antioxidant capacity (T-AOC)) in the liver were examined. The results showed that exogenous rHO1 could significantly upgrade the mRNA expression of HO1 and hepcidin, coupled with increased ROS and T-AOC levels. However, Nrf2 and IL-1ß expression levels were significantly downregulated and upregulated, respectively. These results suggested that HO1 should not only play a protective role in oxidative stress response and its adverse effects deserved further investigation.

Long noncoding RNA CASC9 promotes LIN7A expression via miR-758-3p to facilitate the malignancy of ovarian cancer.

The long noncoding RNA cancer susceptibility 9 (CASC9) has been reported to be a pivot modulator in growth and metastasis of breast cancer, liver cancer, esophageal squamous cell carcinoma, lung adenocarcinoma, gastric cancer, and nasopharyngeal cancer. However, its potential roles in ovarian cancer remain unclear. In this study, we aimed at its functions and molecular mechanism in ovarian cancer progression. We showed that CASC9 was highly expressed in ovarian cancer tissues and cell lines. An elevated level of CASC9 predicts an unfavorable prognosis in patients with ovarian cancer. Loss-of-function and gain-of-function assays illustrated that CASC9 promotes ovarian cancer cell proliferation, migration, and invasion in vitro, and accelerates tumor growth in vivo. We showed that CASC9 works as a competing endogenous RNA (ceRNA) for miR-758-3p which targets LIN7A. CASC9 inhibits the level of miR-758-3p, and in turn stimulates LIN7A expression in ovarian cancer. Overexpression of LIN7A reverses the suppressive roles of CASC9 depletion on ovarian cancer. In sum, our findings reveal a novel undefined regulatory signaling pathway, namely CASC9/miR-758-3p/LIN7A axis, involved in ovarian cancer progression.

Inhibition LC3B can increase chemosensitivity of ovarian cancer cells.

BACKGROUND: Ovarian cancer is often accompanied by the production of ascites, and patients with repeated ascites are associated with chemotherapy resistance. The previous study confirmed that the ovarian cancer patients who developed ascites after chemotherapy had elevated autophagy levels in the ascites and precipitated cells, which was positively correlated with MDR1 expression in the blood of patients. METHODS: In order to explore the correlation between autophagy and chemoresistant, we searched TCGA and GEO database to analyze the correlation between LC3B and MDR1, and identified the targeting miRNA of LC3B. It was verified by dual luciferase that miR-204 can target LC3B. The ovarian cancer cell line and the BALB/c nude mice tumor-bearing model were selected for in vitro and in vivo verification. In vitro studies confirmed that ovarian cancer cells were more sensitive to cisplatin by inhibiting LC3B. RESULTS: Overexpression of miR-204 reduced the expression of LC3B, Atg7, and MDR1, and promoted apoptosis. In vivo studies have also confirmed that reducing the level of autophagy in ovarian cancer cells increases the sensitivity to cisplatin. CONCLUSIONS: It suggests that miR-204 can be used as a tumor suppressor gene and LC3B expression level can be used as a potential molecular marker to guide the diagnosis and treatment of patients with ovarian cancer.

[Establishment of health risk assessment model for assessing medicinal and edible plants contaminated by heavy metals--take Astragali Radix,Codonopsis Radix and Laminariae Thallus as examples].

With the improvement of living standard,the theory of " medicine and food homology" has developed rapidly in the field of diet,medicine and health preservation. In recent years,many literatures have been reported on the active ingredients and pharmacological effects of medicinal and edible plants,but relatively few reports have been reported on their safety investigation. Therefore,to further evaluate the quality and safety of medicinal and edible plants,Astragali Radix,Codonopsis Radix and Laminariae Thallus were selected as our research objects in this study. Moreover,the pollution level and the potential health risk of heavy metals were deeply assessed in different types of medicinal and edible plants. Especially,the contents of chromium,copper,arsenic,cadmium,mercury and lead in these three herbs were determined by inductively coupled plasma mass spectrometry( ICP-MS),and their health risk level was evaluated by target hazard coefficient method. The results showed that under the international heavy metal limit standard( ISO 18664-2015,GB 2762-2017),the over-standard rates were 25%,77% and 100% in 16 batches of Astragali Radix,26 batches of Codonopsis Radix and 9 batches of Laminariae Thallus,respectively. Besides,the values of target hazard quotients( THQ) for adults and children are 0. 028 244,0. 063 505 and 0. 014 485,0. 032 568 in Astragalus membranaceus and Codonopsis pilosula,respectively,which were higher than the standard values of 0. 02 and 0. 011 25. While,the total heavy metals THQ values for adults and children are 0. 023 734 and 0. 020 287 in Laminariae Thallus,which were much higher than the standard values of 0. 008 0 and 0. 007 5. However,the CR values of As,Cd and Pb in the three herbs were lower than 1×10~(-6). Above results indicated that those six harmful elements have certain health hazards to the exposed population,but there is no potential carcinogenic effect. It can be seen that,there were still presence of the pollution of harmful elements,and it is necessary to establish the reasonable limit standards and quality control methods of medicinal and edible plants in time.

[Pollution level and health risk assessment of heavy metals and hazardous elements in Bombyx Batryticatus].

In order to comprehensively analyze the pollution level and bioaccessibility of different types of heavy metals and hazardous elements in animal medicine,this paper selected Bombyx Batryticatus as the research object,and used inductively coupled plasma mass spectrometry( ICP-MS) to detect As,Cu,Hg,Pb,Ni,Cr,Zn and Cd. Based on the artificial gastrointestinal digestion model and the health risk assessment model of Chinese medicinal materials,the pollution level,in vivo and in vitro transfer rate and health risk grade of eight harmful elements in the above-mentioned medicinal materials of Bombyx Batryticatus were obtained respectively. The test result was found that under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 50% for Bombyx Batryticatus,which including 2 batches of As and 4 batches of Cr exceeded the MRL. In artificial gastrointestinal digestion solution,the transfer rates of heavy metals As,Cu,Hg,Pb,Ni,Cr,Zn and Cd were 36. 849%,72. 372%,41. 152%,75. 354%,46. 603%,27. 981%,19. 707% and 76. 282%,respectively. The data of risk assessment model showed that the total THQ values of the most polluted batches for adults and children was 0. 021 548 and 0. 018 418,respectively. After digestion,the THQ values decreased to 0. 012 599 for adults and 0. 010 769 for children,which were still higher than the THQ standard values of animal medicine Bombyx Batryticatus. However,the CR value of carcinogenic risk is less than 1×10-6,so the potential non-carcinogenic risk caused by taking this batch of Bombyx Batryticatus medicines is higher and the carcinogenic risk can be ignored. To sum up,heavy metals and hazardous elements in Bombyx Batryticatus still exceed the standard,but the health risk level caused by heavy metals still needs to be investigated according to different medicinal materials,in order to provide data support for further improving the quality and safety of animal medicine.

[Safety evaluation of heavy metals contaminated Astragalus membranaceus using health risk assessment model].

To evaluate the safety of heavy metals contaminated Astragalus membranaceus,an appropriate protocol was established to study the heavy metals pollution level by health risk assessment. This study provided a detailed procedure to assess the medicinal herbs in quality control and safety evaluation,and expected to create awareness among the public on the safety of consuming of A. membranaceus or any other kinds of medicinal herbs. The heavy metals content of Cu,As,Cd,Pb and Hg in a total of 45 batches of A. membranaceus were carefully analyzed with a developed inductively coupled plasma mass spectrometry( ICP-MS). Besides,the heavy metal contamination level was further evaluated through 4 main assessment parameters,including maximum residue limit( MRL) set by International Standard Organization,estimated daily intake( EDI) set by IUPAC,target hazard quotients( THQ) and Total THQ set by USEPA and total THQs in raw herbs of A. membranaceus. In addition,the recommended MRLs of 5 main heavy metals aimed to A. membranaceus were calculated based on the regulated consumption quantity. The result showed that,under the ISO international standard of Chinese medicine-Chinese herbal medicine heavy metals,the unqualified rate was 8. 89% for A. membranaceus,which including 4 batches of A. membranaceus exceeded the MRL of As. Here,the standard THQ value of A. membranaceus was firstly proposed as 0. 02 and 0. 011 25 for adults and children,respectively,which were calculated with the recommended consumption quantity of 30 g and 9 g for adults and children. Furthermore,the values of THQ for As and total THQs in adults and children were exceeded the standard THQ in A. membranaceus,and the recommended MRLs of Pb,Cd,Hg and Cu in above medicinal materials that calculated based on health risk assessment model were higher than the regulated MRLs that set by ISO and Chinese Pharmacopeia. The research showed that the contents of heavy metals in A. membranaceus were not in the safe range and the certain non-carcinogenic risks to human body cannot be neglected. Based on above investigation result,it is easily known that the common evaluation method for raw herbs based on the comparison of MRL of heavy metals was not precise enough,and the international model of health risk assessment should be built for each medicinal herb. Above all,this study provided a more realistic research approach for safety evaluation of any other kinds of heavy metals contaminated medicinal herbs,including the establishment of heavy metals standard limit in a specified medicinal herb under recommended consumption quantity,and it is expected to create awareness among the public on the safety of consuming any other medicinal herbs.