MEF2C-AS1 regulates its nearby gene MEF2C to mediate cervical cancer cell malignant phenotypes in vitro.

Cervical cancer (CC) is the second most common malignancy among women. GEPIA demonstrated that MEF2C-AS1 and its nearby gene MEF2C present downregulation in CC tissues. We attempted to clarify molecular mechanism between MEF2C-AS1 and MEF2C underlying CC progression. RT-qPCR was used to measure expression levels and subcellular distribution of MEF2C-AS1 and MEF2C in CC cell lines. Gain-of-function assays were conducted to reveal roles of MEF2C-AS1 and MEF2C in CC cell behaviors. Bioinformatics, RNA pull down, and RIP assays were performed to assess association of MEF2C-AS1 or MEF2C with miR-20 b-5p in CC cells. Rescue assays were done to assess regulatory function of the MEF2C-AS1-miR-20 b-5p-MEF2C axis in CC cellular processes. MEF2C-AS1 and its nearby gene MEF2C showed downregulation and had a positive expression correlation in CC tissues. MEF2C-AS1 and MEF2C presented downregulation in CC cells, and they majorly distributed in CC cell cytoplasm. MEF2C-AS1 and MEF2C upregulation repressed CC cell proliferative, migratory, and angiogenic abilities. MEF2C-AS1 competitively bound with miR-20 b-5p to upregulate MEF2C in CC cells. The impacts of MEF2C-AS1 elevation on CC cell proliferative, migratory, and angiogenic capabilities were countervailed by miR-20 b-5p overexpression. The impacts of miR-20 b-5p inhibitor on CC cell proliferative, migratory and angiogenic capabilities were countervailed by MEF2C depletion. To sum up, MEF2C-AS1 and its nearby gene MEF2C present downregulation and serve as tumor suppressors in CC cells. MEF2C-AS1 suppresses CC cell malignancy in vitro through sponging miR-20 b-5p to upregulate MEF2C, which may provide a potential new direction for seeking therapeutic plans of CC.

Phthalates in skin wipes: Distribution, sources, and exposure via dermal absorption.

Phthalates, which are widely used in industrial products, can be dermally absorbed into the human body and harm human health. In this study, we measured the levels of phthalates in skin wipes collected from 30 undergraduate volunteers. The body surfaces wiped include the forehead, forearms, hands, back, calves, and insteps. We analyzed the characteristics and possible sources of phthalates on the skin surface and used Monte Carlo simulations to estimate dermal exposure. The mean total dermal exposure was in the range of 0.129-8.25 µg/(kg·day). Seven phthalates were detected, with a detection frequency of 57-100%. Phthalate levels were not significantly different between symmetrical locations, but differed significantly at the same sampling location. The mean dinonyl phthalate (DNP) contribution was the highest on the forehead, back, and forearm. The mean DNP and di (2-n-butoxyethyl) phthalate (DBEP) contributions on hands were the highest and second-highest, respectively. The mean DBEP contribution was the highest on calf and instep. Phthalates level was the maximum on the forehead and instep. Habit and activities can lead to significant differences in phthalate concentrations on the skin surfaces of male and female students. The sum of dermal exposure on the torso, head, and feet perhaps best approximates the total body exposure. To date, information on the dermal exposure and related species of phthalates are limited; therefore, further study is needed.

External treatment of traditional Chinese medicine for cancer pain: A systematic review and network meta-analysis.

BACKGROUND: Cancer pain is one of the most intolerable and frightening symptoms of cancer patients. However, the clinical effect of the three-step analgesic ladder method (TSAL) is not satisfactory. The combination of external treatment of traditional Chinese medicine (TCM) can improve the clinical effect. OBJECTIVE: This study used network meta-analysis to compare the effects of different external treatment methods of TCM combined with TSAL on cancer pain. METHODS: Databases searched by our team included Google Scholar, Web of Science, Scopus, Embase, PubMed, and Cochrane Library. Randomized controlled trials related to the external treatment of TCM combined with TSAL for cancer pain were screened from the establishment of the database till now. The above literature extracted clinical efficacy, NRS score, KPS score, analgesic onset time, and duration as the main results after the screening. The 95% confidence interval (95% CI) of OR value and SMD value was used as the effect index to compare the difference in efficacy of different interventions, and the ranking was conducted. STATA 17.0 software was used for the statistical analysis of the above data. RESULTS: A total of 78 studies were included, including 8 interventions and 5742 participants. Based on ranking probability, the clinical effective rate of manual acupuncture combined with TSAL was the best when the intervention time was set at 4 weeks [OR = 5.42, 95% CI (1.99,14.81)], and the improvement effect on KPS score was also the best [SMD = 0.97, 95% CI (0.61, 1.33)]. Acupoint external application was the best intervention in reducing NRS score [SMD = -1.14, 95% CI (-1.90, -0.93)]. Acupoint moxibustion combined with TSAL was considered to be the most effective intervention to prolong the duration of analgesia [SMD = 1.69, 95% CI (0.84, 2.54)] and shortening the onset time of analgesia [SMD = -3.00, 95% CI (-4.54, -1.47)]. CONCLUSIONS: TSAL combined with manual acupuncture is the best in terms of clinical efficacy and improvement of patients' functional activity status. With the extension of treatment time, the intervention of this kind of treatment on the clinical effect is more pronounced. Acupoint external application also has a unique advantage in reducing the pain level of patients. From the point of view of analgesic duration and duration of analgesia, combined acupoint moxibustion has the best effect.

A generalization performance study on the boosting radiotherapy dose calculation engine based on super-resolution.

PURPOSE: During the radiation treatment planning process, one of the time-consuming procedures is the final high-resolution dose calculation, which obstacles the wide application of the emerging online adaptive radiotherapy techniques (OLART). There is an urgent desire for highly accurate and efficient dose calculation methods. This study aims to develop a dose super resolution-based deep learning model for fast and accurate dose prediction in clinical practice. METHOD: A Multi-stage Dose Super-Resolution Network (MDSR Net) architecture with sparse masks module and multi-stage progressive dose distribution restoration method were developed to predict high-resolution dose distribution using low-resolution data. A total of 340 VMAT plans from different disease sites were used, among which 240 randomly selected nasopharyngeal, lung, and cervix cases were used for model training, and the remaining 60 cases from the same sites for model benchmark testing, and additional 40 cases from the unseen site (breast and rectum) was used for model generalizability evaluation. The clinical calculated dose with a grid size of 2 mm was used as baseline dose distribution. The input included the dose distribution with 4 mm grid size and CT images. The model performance was compared with HD U-Net and cubic interpolation methods using Dose-volume histograms (DVH) metrics and global gamma analysis with 1%/1 mm and 10% low dose threshold. The correlation between the prediction error and the dose, dose gradient, and CT values was also evaluated. RESULTS: The prediction errors of MDSR were 0.06-0.84% of Dmean indices, and the gamma passing rate was 83.1-91.0% on the benchmark testing dataset, and 0.02-1.03% and 71.3-90.3% for the generalization dataset respectively. The model performance was significantly higher than the HD U-Net and interpolation methods (p < 0.05). The mean errors of the MDSR model decreased (monotonously by 0.03-0.004%) with dose and increased (by 0.01-0.73%) with the dose gradient. There was no correlation between prediction errors and the CT values. CONCLUSION: The proposed MDSR model achieved good agreement with the baseline high-resolution dose distribution, with small prediction errors for DVH indices and high gamma passing rate for both seen and unseen sites, indicating a robust and generalizable dose prediction model. The model can provide fast and accurate high-resolution dose distribution for clinical dose calculation, particularly for the routine practice of OLART.

Mobile health-based remote interaction management intervention for patients with low anterior resection syndrome: study protocol for a randomised controlled trial.

INTRODUCTION: Low anterior resection syndrome (LARS) involves bowel dysfunction after sphincter-preserving surgery for rectal resection that significantly impacts patients' quality of life (QoL). The improvement of LARS largely depends on patient self-management behaviour; however, insufficient information about supportive care and weak awareness of self-management lead to poor self-management behaviour. Motivational interviewing (MIs) explore and change patients' ambivalence during the conversation, thereby changing and maintaining healthy behaviours to enhance effective participation. In recent years, mobile health has been widely used in clinical practice, providing continuous information support and remote interaction. However, current online information on LARS is suboptimal, websites are highly variable, important content is often lacking and the material is too complex for patients. Therefore, this study will evaluate the impacts of a remote LARS interaction management intervention based on a WeChat applet ('e-bowel safety') and MIs on patients with LARS. METHODS AND ANALYSIS: This study will be a single-blind, two-arm randomised controlled trial involving patients with LARS in three tertiary grade A general hospitals who will be randomised into two groups. The intervention group will use the 'e-bowel safety' applet and the intervention team will conduct a monthly MI about syndrome management. The control group will receive an information booklet that contains the same information as that provided in the 'e-bowel safety' informational module. The intervention will last for 3 months, followed by 3 months of follow-up. The primary outcome will be global QoL; the secondary outcomes will include bowel function, social support, self-management measured at the baseline, 3 months and 6 months for three times and patients' thinkings at the end of the intervention (at 3 months). ETHICS AND DISSEMINATION: Ethics approval was granted by the Clinical Medical Research Ethics Committee of the First Affiliated Hospital of Anhui Medical University (PJ2022-07-53). TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry (ChiCTR2200061317).

miR-26a-5p Inhibit Gastric Cancer Cell Proliferation and Invasion Through Mediated Wnt5a.

PURPOSE: Gastric cancer (GC) is a malignant disease of digestive tract. Clinically, radiation therapy is widely applied in treating GC, while with undesirable outcome due to tumor re-proliferation and recurrence and metastasis after radiation. Therefore, it is crucial to explore potential molecular mechanisms to develop therapeutic strategies. The present study found that miR-26a-5p has low expression in GC patients and could regulate Wnt5a to inhibit tumor growth, which was a potential therapeutic target for GC. To explore the expression and related mechanism of miR-26a-5p and Wnt5a in GC. PATIENTS AND METHODS: MiR-26a-5p and Wnt5a were extracted from the transcriptome data of GC downloaded from TCGA database for analysis. The expression levels of miR-26a-5p and Wnt5a in patients' tissues and serum were detected by qRT-PCR, and their correlation with patients' pathological data and survival was analyzed. In addition, miR-26a-5p and Wnt5a overexpression and inhibition vectors were transfected into cells to observe the effects on the proliferation, invasion and apoptosis of GC cells. The relationship between miR-26a-5p and Wnt5a was analyzed by dual luciferase report. RESULTS: The database and clinical samples showed that miR-26a-5p level was low while Wnt5a was high in GC. MiR-26a-5p level decreased in patients with stage III+IV, lymphatic metastasis and tumor ≥3cm, and Wnt5a was contrary to that of the miR-26a-5p, with diagnostic value. Overexpressed miR-26a-5p and inhibited Wnt5a enhanced apoptosis, decreased proliferation and invasion, reduced Bcl-2 and ß-catenin proteins, and elevated Caspase 3, E-cadherin and Bax proteins, while inhibited miR-26a-5p and over-expressed Wnt5a showed the opposite results. Dual luciferase report confirmed that miR-26a-5p targeted to regulate Wnt5a, and rescue experiments found that these effects could be counteracted by reducing miR-26a-5p level. CONCLUSION: Overexpressed miR-26a-5p can inhibit Wnt5a expression, promote cell apoptosis, and suppress cell proliferation and invasion in GC.

Correlation between gamma passing rate and complexity of IMRT plan due to MLC position errors.

PURPOSE: This study evaluates the correlation between the susceptibility of the γ passing rate of IMRT plans to the multi-leaf collimator (MLC) position errors and a quantitative plan complexity metric. METHODS: Twenty patients were selected for this study. For each patient, two IMRT plans were generated using sliding window and step-&-shoot techniques, respectively. Modulation complexity score (MCS) was calculated for all IMRT plans, and symmetric MLC leaf bank errors, ranging from 0.3 mm to 1 mm, were introduced. Original and modified plans were delivered using Varian's Clinac iX. The obtained dose distribution using ArcCHECK was then compared with the TPS calculated dose distribution of the original plans. 3D gamma analysis was performed for each verification with passing criteria of 2%/2 mm. The γ passing rate decreasing gradient were calculated to evaluate relationship between variation of γ passing rate due to MLC errors and complexity. RESULTS: A linear regression analysis was applied between γ gradient and complexity, and the results showed a linear correlation (R2 = 0.81 and 0.82 for open and closed MLC error types, respectively) indicating the more complex plans are more susceptible to MLC leaf bank errors. Meanwhile, correlation of re-normalized γ passing rate and complexity for all errors scenarios also presented a strong correlation (r > 0.75). CONCLUSION: The statistics results revealed variation relationship of dosimetry robust of plans with various complexities to MLC errors. Our results also suggested that the observed susceptibility is independent of the delivery techniques.