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Background The study purpose was to make investigation into the influence of XIST on cervical cancer progression and what’s more its potential mechanism. Methods The cervical cancer data sets (lncRNA, miRNA, and mRNA) obtained from TCGA were analyzed with the “mixOmics” R package. Then, the expression of XIST, miR-140-5p, and ORC1 were detected using qRT-PCR and western blot in both tissues and cervical cancer cell lines (Hela and C33A) to verify the bioinformatics analyses results. CCK-8 assay, 5-ethynyl-2′-deoxyuridine (EdU) assays, cell cycle assay and cell apoptosis assay were practiced. Besides, immunohistochemistry staining was operated for the detection of the Ki-67, E-cadherin and vimentin expression in cervical cancer tissues and the apoptosis-related proteins expression (c-caspase3, Bcl-2, total PARP and cleaved PARP) was verified through western blot. And in vivo experiments were implemented. Results MiR-140-5p was down-regulated but XIST and ORC1 were up-regulated in cervical cancer tissues and cell lines. Knocking down of the XIST or ORC1 memorably suppressed cell proliferation, blocked cell cycle, decreased the expression of Bcl-2 while increased the apoptosis rate and the expression of c-caspase3 and cleaved PARP in HeLa and C33A cells. Besides, the results of immunohistochemistry staining showed knocking down the expression of XIST improved the expression levels of E-cadherin and decreased Ki-67 and vimentin expression. And overexpression of miR-140-5p also could inhibit the progression and reverse the influence of XIST and ORC1 in HeLa and C33A cells. Conclusion Our study indicated the effects of XIST/miR-140-5p/ ORC1 axis on the progression of cervical cancer which will shed new light on epigenetic diagnostics and therapeutics in cervical cancer.

Purpose Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. Methods In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. Results MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. Conclusion MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

Objective This study aimed to explore the effect of intraoperative blood salvage (autotransfusion) on coagulation function in the rescue of an obstetric hemorrhage. Methods A total of 65 pregnant women who were diagnosed with placenta previa in our Hospital and gave birth in the hospital were enrolled in the study. All the patients underwent thromboelastography, routine blood tests, and blood coagulation series + D-dimer before and within 30 min of the autologous blood transfusion. The differences in various indicators were evaluated. Results (1) After the autotransfusion, the hemoglobin and neutrophil counts were significantly higher than beforehand, and the platelet count was significantly reduced; the differences were statistically significant (p < .05). (2) There were no significant differences in prothrombin time (PT), fibrinogen, and D-dimer levels before and after the autotransfusion (p > .05). The activated partial thromboplastin time after autotransfusion was shorter than that beforehand, and the difference was statistically significant (p < .05). (3) There were no significant differences in the R value, K value, α value, and MA value of the thromboelastogram before and after the autotransfusion (p > .05). Conclusion After the recovery autotransfusion, the hemoglobin of patients with a massive obstetric hemorrhage increased significantly, while the platelet count decreased, but the coagulation function and thromboelastogram did not change significantly, indicating the autotransfusion did not affect the coagulation function of the obstetric hemorrhage rescue. Thus, it would appear that intraoperative blood salvage can be safely used in the clinical rescue of massive hemorrhaging during cesarean section.

Background: Non-adherence to physician-prescribed medications, especially oral medications, is common in children with inflammatory bowel disease (IBD), and medication non-adherence is associated with poorer outcomes in IBD. Therefore, understanding and improving medication adherence in children with IBD is critical for optimizing treatment and improving treatment outcomes. Despite the relatively high prevalence of IBD in children in China, to date, very little is known about medication adherence in these patients. Objective: The aim of this study was to investigate the prevalence of medication non-adherence and its risk factors in children with IBD in China to provide a basis for developing adherence improvement strategies. Methods: A cross-sectional design was employed. Children (aged <18 years) with IBD who visited the Children’s Hospital, Zhejiang University School of Medicine, from September 2020 to December 2021 were included. Data were collected by a general information questionnaire, the 4-item Medication Adherence Report Scale (MARS-4) and Crohn’s and Colitis Knowledge (CCKNOW) questionnaire. Subsequently, forward stepwise binary logistic regression analysis was performed to determine independent predictors of medication non-adherence. Results: A total of 119children were included in this study. The results showed that 33 (27.73%) and 86 (72.27%) children had poor and good medication adherence, respectively. Of these, 83 (69.75%) had forgotten to take their medications sometimes, often, or always. On binary logistic regression, we found that the incidence of medication non-adherence in children with IBD course of 3 years and above [ OR 4.82 (95% CI : 1.47-15.88); p = 0.01] was significantly higher than that in children with course of 3 months to 1 year, whereas children with higher parental CCKNOW scores [ OR 0.77 (95% CI : 0.67-0.88); p = 0.00] had significantly lower incidence of medication non-adherence than those with lower parental CCKNOW scores, and the results of the correlation between parental knowledge scores of the four categories and children’s medication adherence showed that drug knowledge scores ( r = 0.36, p < 0.00) and complication knowledge scores ( r = 0.24, p = 0.01) were positively correlated with medication adherence. Conclusion: Poor medication adherence in children with IBD in China was common, and forgetting to take medication was the main barrier. Longer disease duration (3 years and above) in children could act as a risk factor for medication adherence, whereas higher level of parental knowledge about IBD could act as a protective factor, and one interesting novel finding was that the level of parental knowledge about drug and complication were significantly correlated with medication adherence in children with IBD. Our results may inform on the design and implementation of medication adherence interventions for children with IBD.

ObjectivesCetuximab plus leucovorin, fluorouracil and oxaliplatin (FOLFOX-4) is superior to FOLFOX-4 alone as a first-line treatment for patients with metastatic colorectal cancer with RAS wild-type (RAS wt mCRC), with significantly improved survival benefit by TAILOR, an open-label, randomised, multicentre, phase III trial. Nevertheless, the cost-effectiveness of these two regimens remains uncertain. The following study aims to determine whether cetuximab combined with FOLFOX-4 is a cost-effective regimen for patients with specific RAS wt mCRC in China.DesignA cost-effectiveness model combined decision tree and Markov model was built to simulate pateints with RAS wt mCRC based on health states of dead, progressive and stable. The health outcomes from the TAILOR trial and utilities from published data were used respectively. Costs were calculated with reference to the Chinese societal perspective. The robustness of the results was evaluated by univariate and probabilistic sensitivity analyses.ParticipantsThe included patients were newly diagnosed Chinese patients with fully RAS wt mCRC.InterventionsFirst-line treatment with either cetuximab plus FOLFOX-4 or FOLFOX-4.Main outcome measuresThe primary outcomes are costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs).ResultsBaseline analysis disclosed that the QALYs was increased by 0.383 caused by additional cetuximab, while an increase of US$62 947 was observed in relation to FOLFOX-4 chemotherapy. The ICER was US$164 044 per QALY, which exceeded the willingness-to-pay threshold of US$28 106 per QALY.ConclusionsDespite the survival benefit, cetuximab combined with FOLFOX-4 is not a cost-effective treatment for the first-line regime of patients with RAS wt mCRC in China.Trial registration numberTAILOR trial (NCT01228734); Post-results.

Background: Tacrolimus (TAC) is an important immunosuppressant for children with primary nephrotic syndrome (PNS). The relationship between sampling time variability in TAC therapeutic drug monitoring and dosage regimen in such children is unknown. Methods: In this single-center, prospective, observational study, we evaluated the sampling time variability, concentration error (CE), relative CE (RCE), and the impact of the sampling time on TAC dosage regimens in 112 PNS children with 188 blood samples. Nominal concentration (C nom ) at 12-h after last TAC dose was simulated based on observed concentration (C obs ) via previously published pharmacokinetic models, then CE and RCE were calculated. Inappropriate dosing adjustments resulting from deviated sampling time were evaluated based on a target C nom of 5–10 ng/ml. Results: We found that 32 and 68% of samples were respectively collected early (2–180 min) and delayed (4–315 min). Furthermore, 24, 22, 22, and 32% of blood samples were drawn within deviations of ≤0.5, 0.5–1, 1–2, and >2 h, respectively, and 0.3 ng/ml of CE and 6% RCE per hour of deviation occurred. Within a deviation of >2 h, 25% of C obs might result in inappropriate dosing adjustments. Early and delayed sampling might result in inappropriate dose holding or unnecessary dose increments, respectively, in patients with C obs ∼ 5 ng/ml. Conclusions: Variable sampling time might lead to inappropriate dosing adjustment in a minority of children with PNS, particularly those with TAC C obs ∼ 5 ng/ml collected with a deviation of >2 h.

[This corrects the article DOI: 10.3389/fphar.2021.726667.].[This corrects the article DOI: 10.3389/fphar.2021.726667.].

Graphene possesses unique physical and chemical properties, which have inspired a wide range of potential biomedical applications. However, little is known about the adverse effects of graphene on the human body and ecological environment. The purpose of our work is to make assessment on the toxicity of graphene oxide （GO） against human cell line （human bone marrow neuroblastoma cell line and human epithelial carcinoma cell line） and zebrafish （Danio rerio） by comparing the toxic effects of GO with its sister, multi-walled carbon nanotubes （MWNTs）. The results show that GO has a moderate toxicity to organisms since it can induce minor （about 20%） cell growth inhibition and slight hatching delay of zebrafish embryos at a dosage of 50 mg/L, but did not result in significant increase of apoptosis in embryo, while MWNTs exhibit acute toxicity leading to a strong inhibition of cell proliferation and serious morphological defects in developing embryos even at relatively low concentration of 25 mg/L. The distinctive toxicity of GO and MWNTs should be ascribed to the different models of interaction between nanomaterials and organisms, which arises from the different geometric structures of nanomaterials. Collectively, our work suggests that GO does actual toxicity to organisms posing potential environmental risks and the result is also shedding light on the geometrical structure-dependent toxicity of graphitic nanomaterials.

Background Although the clinical efficacy and safety of repetitive transcranial magnetic stimulation (rTMS) in the treatment of chronic tinnitus have been frequently examined, the results remain contradictory. Therefore, we performed a systematic review and meta-analysed clinical trials examining the effects of rTMS to evaluate its clinical efficacy and safety. Methods Studies of rTMS for chronic tinnitus were retrieved from PubMed, Embase, and Cochrane Library through April 2020. Review Manager 5.3 software was employed for data synthesis, and Stata 13.0 software was used for analyses of publication bias and sensitivity. Results Twenty-nine randomized studies involving 1228 chronic tinnitus patients were included. Compared with sham-rTMS, rTMS exhibited significant improvements in the tinnitus handicap inventory (THI) scores at 1 week (mean difference [MD]: − 7.92, 95% confidence interval [CI]: − 14.18, − 1.66), 1 month (MD: -8.52, 95% CI: − 12.49, − 4.55), and 6 months (MD: -6.53, 95% CI: − 11.406, − 1.66) post intervention; there were significant mean changes in THI scores at 1 month (MD: -14.86, 95% CI: − 21.42, − 8.29) and 6 months (MD: -16.37, 95% CI: − 20.64, − 12.11) post intervention, and the tinnitus questionnaire (TQ) score at 1 week post intervention (MD: -8.54, 95% CI: − 15.56, − 1.52). Nonsignificant efficacy of rTMS was found regarding the THI score 2 weeks post intervention (MD: -1.51, 95% CI: − 13.42, − 10.40); the mean change in TQ scores 1 month post intervention (MD: -3.67, 95% CI: − 8.56, 1.22); TQ scores 1 (MD: -8.97, 95% CI: − 20.41, 2.48) and 6 months (MD: -7.02, 95% CI: − 18.18, 4.13) post intervention; and adverse events (odds ratios [OR]: 1.11, 95% CI: 0.51, 2.42). Egger’s and Begg’s tests indicated no publication bias ( P  = 0.925). Conclusion This meta-analysis demonstrated that rTMS is effective for chronic tinnitus; however, its safety needs more validation. Restrained by the insufficient number of included studies and the small sample size, more large randomized double-blind multi-centre trials are needed for further verification.

Chronic hepatitis B (CHB) is an infectious viral disease that is prevalent worldwide. Traditional nucleoside analogues, as well as the novel drug targets against hepatitis B virus (HBV), are associated with certain critical factors that influence the curative effect, such as biological stability and safety, effective drug delivery, and controlled release. Nanoparticle drug delivery systems have significant advantages and have provided a basis for the development of anti-HBV strategies. In this review, we aim to review the advances in nanoparticle drug delivery systems for anti-hepatitis B virus therapy by summarizing the relevant literature. First, we focus on the characteristics of nanoparticle drug delivery systems for anti-HBV therapy. Second, we discuss the nanoparticle delivery systems for anti-HBV nucleoside drugs, gene-based drugs, and vaccines. Lastly, we provide an overview of the prospects for nanoparticle-based anti-HBV agents.