N6-methyladenosine (m6A) as a regulator of carcinogenesis and drug resistance by targeting epithelial-mesenchymal transition and cancer stem cells.

Emergence of drug resistance to chemotherapeutic agents is the principal obstacle towards curative cancer treatment in human cancer patients. It is in an urgent to explore the underlying molecular mechanisms to overcome the drug resistance. N6-Methyladenosine (m6A) RNA modification is the most abundant reversible RNA modification and has emerged in recent years to regulate gene expression in eukaryotes. Recent evidence has identified m6A is associated with cancer pathogenesis and drug resistance, contributing to the self-renewal and differentiation of cancer stem cell, tumor epithelial-mesenchymal transition (EMT) and tumor metastasis. Here we reviewed up-to-date knowledge of the relationship between m6A modulation and drug resistance. Furthermore, we illustrated the underlying mechanisms of m6A modulation in drug resistance. Lastly, we discussed the regulation of m6A modulation in EMT and cancer stem cells. Hence, it will help to provide significant therapeutic strategies to overcome drug resistance for cancer patients by changing m6A-related proteins via targeting cancer stem cells and EMT-phenotypic cells.

Correlation between three-dimensional transperineal ultrasound and pelvic floor electromyography in women with stress urinary incontinence.

OBJECTIVES: To investigate the relationships among pelvic floor myoelectric level, ultrasound and stress urinary incontinence in women. MATERIAL AND METHODS: 218 women with SUI and 300 normal women were studied. The main outcomes were to determine the relationship between SUI and high-risk factors, PFM intensity, pelvic floor EMG value, and pelvic floor ultrasound data. RESULTS: In the pelvic floor EMG data, the abnormal rate of type I muscle fibre strength, type I muscle fibre fatigue, type II muscle fibre strength and type II muscle fibre endurance in the SUI group reached more than 50%. The abnormal rates of type I muscle fibre strength and type II muscle fibre strength in the severe SUI group were more significant than those in the mild and moderate SUI. The funnelization of the black neck urethra, bladder neck mobility, posterior angle of the black neck urethra, urinary increment angle and urinary rotation angle of the SUI group were significantly increased. The levator ani muscle in the SUI group was thinner, and the difference was statistically significant. The analysis of the variance results of the overall significance of the regression model were tested, and the final multiple linear regression model was statistically significant. CONCLUSIONS: With the help of a convenient and economic means of the early detection of SUI, the diagnosis rate can be improved so that SUI tendency can achieve a diagnosis and treatment through nonsurgical treatment with fewer complications and a low risk and improve the quality of life of middle-aged and elderly women.

Anlotinib inhibits the proliferation and induces apoptosis by inactivating the AKT pathway in androgen receptor-negative prostate cancer cells.

Prostate cancer is one of the most frequently diagnosed cancers in men. The medical treatment of metastatic prostate cancer relies heavily on androgen deprivation. The present study aimed to explore the inhibitory effect of anlotinib on androgen receptor (AR)-negative prostate cancer cell lines in vitro and investigate its mechanism of action. Two prostate cancer cell lines, DU145 and PC-3, were treated with different concentrations (0-80 µM) of anlotinib. Cell proliferation was accessed by CCK-8 assay and EdU staining. Cell nuclear morphology was observed after DAPI staining, cell apoptosis level was evaluated by Annexin-V-FITC/PI staining, and western blot was used to detect the proliferation- and apoptosis-related proteins. The potential interaction between anlotinib and AKT was revealed by molecular docking. After treatment with anlotinib, the cell proliferation rate was significantly inhibited in a dose-dependent manner. The DAPI staining showed that anlotinib could induce apoptosis. Further, Annexin V/PI double staining confirmed the occurrence of apoptosis, accompanied by the increase of cleaved caspase-3 and activated PARP. Moreover, anlotinib significantly decreased the phosphorylation of protein kinase B (AKT) and its downstream pathway proteins in prostate cells (p<0.05). Experiments further confirmed that the activation of the AKT pathway reversed the inhibitory effect of anlotinib on DU145 and PC-3 cell proliferation. In addition, molecular docking analysis revealed potential interactions between anlotinib and AKT1 at multiple sites. Overall, the present study suggested that anlotinib could inhibit the proliferation and induce apoptosis in the AR-negative prostate cancer cell lines, possibly via the inactivation of the AKT pathway.

Value of endorectal ultrasonography in the assessment of invasion staging of low rectal cancer with local progression after neoadjuvant radiochemotherapy / Valor de la ultrasonografía endorectal en la evaluación de la estadificación de la invasión del cáncer rectal bajo con progresión local, después de administrar radioquimioterapia neoadyuvante

Abstract Although stages T3 and T4 rectal cancer can be reduced to T1 or T2 after neoadjuvant radiochemotherapy, the accuracy of the endorectal ultrasonography (ERUS) for the post-radiochemotherapy evaluation of low rectal cancer has seldom been reported. We aimed to investigate the value of ERUS in the assessment of invasion staging in low rectal cancer with local progression, and the factors affecting its accuracy, after neoadjuvant radiochemotherapy. A total of 114 patients administered with neoadjuvant radiochemotherapy for stages II and III low rectal cancer (local stage T3/T4) from February 2018 to December 2020 were enrolled in the study. The changes in local lesions were evaluated using ERUS before and after radiochemotherapy, and compared with the pathological T staging. The accuracy of post-neoadjuvant radiochemotherapy re-staging examined with ERUS was evaluated, and univariate analysis was used to identify the factors affecting the accuracy. After neoadjuvant radiochemotherapy, the blood flow distribution within the lesion significantly declined (P<0.05), the max length and max thickness of the longitudinal axis of the lesion were reduced (P<0.05), and the uT staging was decreased (P<0.05), when compared with lesions before the treatment. Compared with postoperative pathological T staging, the accuracies of ERUS in T1, T2, T3 and T4 stages were 11.11%, 28.57%, 27.27% and 100%, respectively. Univariate analysis indicated that review time of ERUS, post-operative T staging and Wheeler rectal regression stage were factors affecting the accuracy of ERUS re-staging. ERUS is more accurate for T4 re-staging, follow-up reviewed six weeks after neoadjuvant radiochemotherapy and low regression tumors, with a high application value for the assessment of the efficacy of neoadjuvant radiochemotherapy for low rectal cancer.

Resumen Aunque el cáncer de recto en estadios T3 y T4 se puede reducir a T1 o T2 después de la radioquimioterapia neoadyuvante, rara vez se ha informado la precisión de la ecografía endorrectal (ERUS) para la evaluación posterior a la radioquimioterapia del cáncer de recto inferior. Nuestro objetivo fue investigar el valor de ERUS en la evaluación de la estadificación de la invasión en el cáncer de recto inferior con progresión local, después de la radioquimioterapia neoadyuvante y los factores que afectan su precisión. Se incluyeron en el estudio un total de 114 pacientes a los que se les administró radioquimioterapia neoadyuvante para el cáncer de recto inferior en estadios II y III (estadio local T3/T4), desde febrero de 2018 hasta diciembre de 2020. Los cambios en las lesiones locales se evaluaron mediante ERUS antes y después de la radioquimioterapia y se compararon con la estadificación patológica T. Se evaluó la precisión de la re-estadificación examinada con ERUS, después de la radioquimioterapia neoadyuvante y se utilizó un análisis univariado para identificar los factores que afectan su precisión. Después de la radioquimioterapia neoadyuvante, la distribución del flujo sanguíneo dentro de la lesión disminuyó significativamente (P<0,05), la longitud máxima y el espesor máximo del eje longitudinal de la lesión se redujeron (P<0,05) y la estadificación uT disminuyó (P<0,05), en comparación con las lesiones antes del tratamiento. En comparación con la estadificación T patológica posoperatoria, las precisiones de ERUS en las etapas T1, T2, T3 y T4 fueron del 11,11%, 28,57%, 27,27% y 100%, respectivamente. El análisis univariable indicó que el tiempo de revisión de ERUS, la estadificación T postoperatoria y la etapa de regresión rectal de Wheeler fueron factores que afectaron la precisión de la re-estadificación con ERUS. ERUS es más preciso para la re-estadificación de T4, el seguimiento seis semanas después de la radioquimioterapia neoadyuvante y en tumores de baja regresión, con un alto valor de aplicación para la evaluación de la eficacia de la radioquimioterapia neoadyuvante para el cáncer rectal bajo.

A comparison of trans-fistula contrast-enhanced endoanal ultrasound and MRI in the diagnosis of anal fistula.

BACKGROUND: Many hospitals favor magnetic resonance imaging (MRI) as the preferred diagnostic method to detect anal fistula, trans-fistula contrast-enhanced ultrasound (CEUS) for the diagnosis of anal fistula have attracted the attention of investigators worldwide. This study aimed to investigate the efficacy of trans-fistula contrast-enhanced endoanal ultrasound (CEUS) and magnetic resonance imaging (MRI) in the diagnosis of anal fistula. METHODS: Ninety-eight patients undergoing trans-fistula CEUS and MRI were retrospectively analyzed. The fistulous trend and positional relation between the fistula, levator ani muscle, and sphincter (Parks classification), as well as the numbers of fistulous branches, number and position of the fistula, and distance between internal opening and anal edge were recorded. These parameters were compared with the postoperative results. RESULTS: There were no significant statistical differences (P>0.05) in the accuracy rates of trans-fistula CEUS and MRI, respectively, in terms of Parks classification (90.82%, 92.86%), branches (89.19%, 81.08%), internal openings (92.68%, 89.43%), and internal openings ≥3 cm from the anal edge (85.71%, 92.86%). However, we observed a significant difference in terms of internal openings <3 cm from the anal edge (96.30%, 87.65%) (P=0.043). CONCLUSIONS: Although both methods exhibited a perfect accuracy rate in diagnosing anal fistula, trans-fistula CEUS displayed superior diagnostic value for internal openings <3 cm from the anal edge, and could provide reliable pre-operative evidence.

Application value of conventional ultrasound combined with shear wave elastography in diagnosing triple negative breast cancer.

BACKGROUND: At present, most ultrasound (US) studies on triple negative breast cancer (TNBC) are limited to conventional US features, so it is necessary to develop new joint diagnostic methods. The study aims to explore the values of conventional US and shear wave elastography (SWE) in differential diagnoses of TNBC and non-TNBC. METHODS: A total of 120 breast cancer (BC) patients involving 120 lesions that were pathologically verified were retrospectively analyzed in this study. All participants had received both conventional US and SWE before surgery. Meanwhile, the participants were divided into a TNBC group or a non-TNBC group according to their immunohistochemical (IHC) results. The differences between the conventional US features (including lesion shape, growth location, margin, boundary, internal echo, micro-calcification, posterior echo, and internal blood supply) and the SWE image features [including mean lesion hardness (Emean), maximum (Emax), minimum (Emin), standard deviation (SD), and ratio to normal gland (Eratio)] of 2 groups were compared. The receiver operating characteristic (ROC) curve of the diagnosed lesion was calculated by the area under the curve (AUC). RESULTS: According to the findings of conventional US, the TNBC group mostly manifested as a micro-lobulated margin, with a clear boundary and no internal micro-calcification; the non-TNBC group mainly manifested as marginal angulation or burr, and hyper-echo halo in the boundary, accompanied with internal micro-calcification, and the difference was statistically significant (P<0.05); the internal thrombolysis in myocardial infarction (TIMI) and resistance index between the TNBC group and non-TNBC group were similar, and the differences were not statistically significant (P>0.05). The findings of SWE were as follows: differences in Emax, Emean, and Eratio values between 2 groups were statistically significant (P<0.05); and the areas under the ROC curve (AUC) of these three in diagnosing the lesions were 0.811, 0.781 and 0.770, respectively. CONCLUSIONS: Conventional US combined with SWE can comprehensively analyze the morphological, blood supply, and hardness features of breast lesions, and provide more reliable information for the differential diagnosis between TNBC and non-TNBC.

Serum long non­coding RNA NNT­AS1 protected by exosome is a potential biomarker and functions as an oncogene via the miR­496/RAP2C axis in colorectal cancer.

Increasing evidence has indicated that long non­coding RNAs (lncRNAs) serve an essential role in carcinogenesis and cancer development. It has been reported that lncRNA nicotinamide nucleotide transhydrogenase antisense RNA 1 (NNT­AS1) serves a crucial role in several types of cancer. However, the clinical significance of circulating NNT­AS1 expression in colorectal cancer (CRC) remains to be elucidated. The current study aimed to investigate the potential role of NNT­AS1 and the clinical significance of its serum expression levels in patients with CRC. The expression of NNT­AS1 was measured in 40 pairs of tumor and adjacent normal tissues from patients with CRC via reverse transcription­quantitative PCR. The serum expression levels of NNT­AS1 were assayed in an independent cohort of healthy controls and patients with CRC. The levels of NNT­AS1 were also compared between paired preoperative and postoperative serum samples. In addition, the presence of exosomal NNT­AS1 in serum was explored. Furthermore, the biological roles of NNT­AS1 were investigated in CRC cells in vitro. The expression of NNT­AS1 was significantly upregulated in tumor tissues compared with adjacent normal tissues (P<0.05). A higher level of NNT­AS1 was associated with an advanced CRC stage. The serum levels of NNT­AS1 were significantly upregulated in patients with CRC compared with healthy subjects (P<0.05). Furthermore, the NNT­AS1 levels were significantly decreased in postoperative samples compared with preoperative samples (P<0.01). In addition, it was also identified that NNT­AS1 was upregulated in CRC exosomes (P<0.01), whereas no significant difference was observed in NNT­AS1 levels between serum and exosomes. Silencing of NNT­AS1 inhibited the proliferation, migration and invasion of CRC cells. It was also identified that NNT­AS1 exerted its effects via regulation of the microRNA­496/Ras­related protein Rap­2c axis. The present study demonstrated that circulating NNT­AS1, which may be protected by exosomes, could be a novel potential biomarker and therapeutic target in CRC.

Transition-Metal-Free One-Step Synthesis of Ynamides.

A robust transition-metal-free one-step strategy for the synthesis of ynamides from sulfonamides and ( Z)-1,2-dichloroalkenes or alkynyl chlorides is presented. This method is not only effective for internal ynamides but also amenable for terminal ynamides. Various functional groups, even the vinyl moiety, are compatible, and thus, this strategy offers the opportunity for further functionalization.

Determinants of sleep quality among pregnant women in China: a cross-sectional survey.

PURPOSE: Sleep disturbances are common during pregnancy, yet few studies are currently available regarding the determinants of sleep quality among pregnant women in China. This study aimed to: (a) calculate the prevalence of sleep disorder during pregnancy, (b) examine the difference in sleep quality among three trimesters, and (c) identify determinants of sleep quality in pregnant women. MATERIALS AND METHODS: This study was designed as a cross-sectional survey. Five hundred pregnant women were recruited at the outpatient department of obstetrics and gynecology of two teaching hospitals in central China. Five selfreport questionnaires were used for gathering data, including information of sample characteristics, sleep quality (Pittsburgh Sleep Quality Index (PSQI)), prenatal depression (the Edinburgh Postnatal Depression Scale (EPDS)), perceived stress (Perceived Stress Scale (PSS)), and perceived social support (Multidimensional Scale of Perceived Social Support (MSPSS)). RESULTS: A total of 454 pregnant women participated in the study between September 2016 and April 2017. Eighty-seven percent pregnant women experienced sleep disorder (PSQI score >5). Poorer global sleep quality, subjective sleep quality, lower sleep efficiency and sleep disturbances were most prevalent during third trimester. The significant contributors to sleep quality for pregnant women were prenatal depression, maternal age, and gestational age. CONCLUSIONS: Sleep disorder is very common in pregnant women from China. Depressive symptoms, increased maternal age, and gestational age are determinants of sleep quality. These determinants can assist healthcare professionals in preventative intervention.

Risk factors of chronic obstructive pulmonary disease among adults in Chinese mainland: A systematic review and meta-analysis.

BACKGROUND: Identifying risk factors is a key point for preventive strategies to reduce the incidence of COPD. The aim of this systematic review and meta-analysis was to determine the most important risk factors for COPD among adults in Chinese Mainland, so as to provide some precautions and interventions on this disease and preventing further recurrences. METHODS: A comprehensive literature review relating to risk factors for COPD through PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang database and VIP database was conducted before March 31, 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated after data combination to assess the associations between risk factors and COPD. Heterogeneity between the studies was assessed by I2 and Cochran's Q test. Egger's test was used to assess publication bias. RESULTS: A total of 13893 participants (6383 cases and 7510 controls) from 19 case-controls studies were included. 12 risk factors with significant differences found between COPD and control groups were listed as follows: male sex (OR = 1.467; 95%CI: 1.097-1.962), smoking (OR = 2.092; 95%CI: 1.707-2.565), low educational level (OR = 1.609; 95%CI: 1.206-2.147), low BMI (OR = 3.831; 95%CI: 2.223-6.603), family history of respiratory disease (OR = 2.068; 95%CI: 1.466-2.918), allergy history (OR = 2.381; 95%CI: 1.385-4.093), respiratory infection during childhood (OR = 2.695; 95%CI: 1.504-4.828), recurrent respiratory infection (OR = 15.015; 95%CI: 4.538-49.684), occupational dust exposure (OR = 1.791; 95%CI: 1.151-2.788), biomass burning (OR = 2.218; 95%CI: 1.308-3.762), poor housing ventilation (OR = 3.993; 95%CI: 1.244-12.820), and living around polluted area (OR = 1.631; 95%CI: 1.202-2.214). CONCLUSION: Twelve risk factors are associated with the occurrence of COPD in Chinese Mainland, which can be used to distinguish high-risk population. Health education and promotion campaigns should be designed in order to minimize or prevent the occurrence of COPD in Chinese Mainland.

[Impacts on the life quality of the patients with allergic rhinitis treated with warming acupuncture in winter and summer].

OBJECTIVE: To explore the impacts on the life quality and the effect mechanism in the patients of allergic rhinitis (AR) treated with warm acupuncture in winter and summer. METHODS: Two hundred and forty patients of AR were randomized into a summer and winter acupuncture group, a non-summer and winter acupuncture group and a western medication group, 80 cases in each one. In the two acupuncture groups, Dazhui (GV 14), Fengmen (BL 12), Feishu (BL 13), Pishu (BL 20) and Shenshu (BL 23) were selected. In the summer and winter acupuncture group, the warm acupuncture started at the first day of the three periods of hot season and the first day of the third nine-day period after the winter solstice. The treatment was given once every two days, continuously for 15 times. Totally, 30 treatments were required a year. In the non-summer and winter acupuncture group, the warm acupuncture was applied out of the three periods of the hot season and the third nine-day period after the winter solstice. The treatment was given once every two days and 30 treatments for a year. In the western medication group, cetirizine was taken orally, continuously for 30 days as one session. In the three groups, the treatment for 1 year was taken as one session. The second session started in the next year. Totally, 2 sessions were required. The score of rhinoconjunctivitis quality of life questionnaire (RQLQ) and the level of serum immunoglobulin E (IgE) were compared in the patients' of each group before treatment and in 1 and 2 sessions of treatment. RESULTS: After treatment, the scores of 7 domains, named activities, common complaints, practical problems, sleep, ocular symptoms, nasal symptoms and emotions were all improved as compared with those before treatment, in the patients of the three groups (all P < 0.05). After 2 sessions treatment, the results in the summer and winter acupuncture group were better than those in the other two groups (all P < 0.05), and the results in the non-summer and winter acupuncture group were better than those in the western medication group (all P < 0.05). After treatment, serum IgE level was lower averagely than that before treatment in the three groups (all P < 0.05). After 2 sessions treatment, the result in the summer and winter acupuncture group was lower than that in the other two groups (both P < 0.05), and the result in the non-summer and winter acupuncture group was lower than that in the western medication group (P < 0.05). After treatment, the total effective rate was 92.3% (72/78) in the summer and winter acupuncture group, better than 80.5% (62/77) in the non-summer and winter acupuncture group and 69.7% (53/76) in the western medication group (both P < 0.05). CONCLUSION: The warm acupuncture in both summer and winter achieves the definite efficacy on AR and the effect mechanism is relevant with reducing serum IgE level.