Muscle reconstruction using a five-flap method with a short straight-line incision in unilateral incomplete cleft lip repair.

When performing a unilateral incomplete cleft lip repair, it is essential to create a good sub-structure of the upper lip contour, reconstruct the orbicularis oris muscle, and prevent an unwanted scar. The aim of this study was to investigate the clinical effect of muscle reconstruction using a five-flap method with a short straight-line incision in unilateral incomplete cleft lip repair. Thirty-two infants with unilateral incomplete cleft lip were treated with this method between April 2020 and February 2023. A short straight-line incision was designed along the philtral column. The orbicularis oris muscle was reconstructed with a five-flap method in three areas: nasal base area, white lip area, and red lip area. Patient outcomes were assessed through subjective evaluation and anthropometric measurements. No patient experienced any postoperative complications. The philtral column and Cupid's bow were well reconstructed. Deviation of nasal columella was corrected and the nasal floor was elevated. Functionally and aesthetically satisfactory outcomes were obtained in all patients over long-term follow-up. In conclusion, this technique was able to create a good sub-structure of the nasolabial contour and bring a significant improvement in bilateral symmetry, showing it to be an effective method for incomplete unilateral cleft lip repair with minimal scarring.

[Clinical effects of flaps or myocutaneous flaps transplantation after titanium mesh-retaining debridement in repairing the wounds with exposed titanium mesh after cranioplasty].

Objective: To explore the clinical effects of flaps or myocutaneous flaps transplantation after debridement to repair the wounds with exposed titanium mesh after cranioplasty on the premise of retaining the titanium mesh. Methods: This study was a retrospective observational study. From February 2017 to October 2022, 22 patients with titanium mesh exposure after cranioplasty who met the inclusion criteria were admitted to the Department of Plastic, Aesthetic & Maxillofacial Surgery of the First Affiliated Hospital of Xi'an Jiaotong University, including 15 males and 7 females, aged from 19 to 68 years. After admission, treatments such as bacterial culture of wound exudate sample, anti-infection, and dressing change were carried out. Thorough surgical debridement was performed when the wound improved, and the wound area was 3.0 cm×2.0 cm to 11.0 cm×8.0 cm after debridement. The wound was repaired with local flaps, expanded flaps, or free latissimus dorsi myocutaneous flaps according to the size, location, severity of infection, and surrounding tissue condition of the wounds, and the areas of flaps or myocutaneous flaps were 5.5 cm×4.0 cm to 18.0 cm×15.0 cm. The donor areas of flaps were sutured directly or repaired by split-thickness skin grafts from head. The wound repair method was recorded. The survivals of flaps or myocutaneous flaps after surgery and wound healing in 2 weeks after surgery were recorded. During postoperative follow-up, recurrence of infection or titanium mesh exposure in the implanted area of titanium mesh was observed; the head shapes of patients, scar formation of the operative incision, and baldness were observed. At the last follow-up, the satisfaction of patients with the treatment effect (dividing into three levels: satisfied, basically satisfied, and dissatisfied) was evaluated. The total treatment costs of patients during their hospitalization were calculated. Results: The wounds in 11 cases were repaired with local flaps, the wounds in 5 cases were repaired with expanded flaps, and the wounds in 6 cases were repaired with free latissimus dorsi myocutaneous flaps. All flaps or myocutaneous flaps survived completely after surgery, and all wounds healed well in 2 weeks after surgery. Follow up for 6 to 48 months after operation, only one patient with local flap grafting experienced a recurrence of infection in the titanium mesh implanted area at more than one month after surgery, and the titanium mesh was removed because of ineffective treatment. Except for one patient who had a local depression in the head after removing the titanium mesh, the rest of the patients had a full head shape. Except for myocutaneous flap grafting areas in 6 cases and skin grafting area in 1 case with local flaps grafting had no hair growth, the other patients had no baldness. All the scars in surgical incision were concealed. At the last follow-up, 19 cases were satisfied with the treatment effects, 2 cases were basically satisfied, and 1 case was dissatisfied. The total treatment cost for patients in this group during hospitalization was 11 764-36 452 (22 304±6 955) yuan. Conclusions: For patients with titanium mesh exposure after cranioplasty, on the premise of adequate preoperative preparation and thorough debridement, the wound can be repaired with appropriate flaps or myocutaneous flaps according to the wound condition. The surgery can preserve all or part of the titanium mesh. The postoperative wound healing is good and the recurrence of infection or titanium mesh exposure in the titanium mesh implanted area is reduced, leading to good head shape, reduced surgical frequency, and decreased treatment costs.

[Application of two kinds of electrophysiological monitoring techniques for the prediction of facial nerve outcomes after vestibular Schwannoma surgery].

Objective: To investigate the application of transcranial facial nerve motor evoked potential (FNMEP) and direct nerve electrical stimulation (DNES) for the prediction of facial nerve function after vestibular schwannoma surgery. Methods: The clinical data of 106 patients who underwent vestibular schwannoma surgery under electrophysiological monitoring of facial nerve between 2017 and 2021 were retrospectively examined, and there were 57 males and 49 females, with a mean age of (51±11) years. Neuroelectrophysiological monitoring was performed in all patients during the operation. After the tumor was removed, FNMEP and DNES were used for electrophysiological evaluation of facial nerve function. The amplitude ratios of FNMEP to baseline (M1) and the brainstem segment to the internal auditory canal segment of DNES (M2) were recorded after the tumor was removed, respectively. The correlation between these two ratios and facial nerve function at 1 day, 1 month and 3 months after the operation were compared. According to the House-Brackmann (HB) scale, Grade Ⅰ-Ⅱ refers to good facial nerve function, and grade Ⅲ-Ⅵ refers to moderate and severe facial nerve dysfunction. Non-parameter Spearman correlation coefficient was used to evaluate the correlation between M1 and M2 and facial nerve function at 1 day, 1 month and 3 months after operation, and the receiver operating characteristic (ROC) curves were plotted to verify the diagnostic efficacy of M1 and M2 for predicting the prognosis of postoperative facial nerve function. Results: Among 106 patients, 102 cases (96.3%) underwent total tumor resection, 4 patients (3.7%) underwent subtotal resection, 104 patients (98.1%) had anatomical preservation of facial nerves, and there were no deaths reported. All patients could evoke reliable FNMEP and 2 patients could not evoke DNES in the brainstem segment of the facial nerve. There were 81 (76.4%), 99 (93.4%) and 103 patients (97.2%) with satisfactory function of facial nerve at 1 day, 1 month and 3 months after surgery, respectively. M1 had large absolute values of Spearman correlation coefficient at 1 day (ρ=|-0.648|) and 1 month (ρ=|-0.552|) after surgery (both P<0.001), while M2 showed a greater absolute value of Spearman correlation coefficient at 3 months (ρ=|-0.395|) than that of M1 (ρ=|-0.378|) (P<0.001). Cut-off value of M1 was 0.58 (sensitivity=0.92, specificity=0.64), and that of M2 was 0.36 (sensitivity=0.64, specificity=1.00). Meanwhile, M1<0.58 or M2<0.36 suggested moderate and severe impairment of facial nerve function. Conclusions: Both FNMEP and DNES during vestibular schwannoma surgery can effectively evaluate the postoperative facial nerve function. FNMEP is better than DNES in predicting the early postoperative facial nerve function, but DNES is better for predicting the long-term postoperative facial nerve function.

Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9.

The article "Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9, by Z.-H. Liu, W.-J. Liu, X.-Y. Yu, X.-L. Qi, C.-C. Sunu, published in Eur Rev Med Pharmacol Sci 2020; 24 (20): 10375-10382-DOI: 10.26355/eurrev_202010_23387-PMID: 33155193" has been retracted by the authors due to inaccuracies related to the misuse of Table I. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/23387.

circRNA CRIM1 regulates the migration and invasion of bladder cancer by targeting miR182/Foxo3a axis.

PURPOSE: To explore the molecular mechanism of circRNA CRIM1 in the regulation of bladder cancer by targeting the miR182/Foxo3a axis. METHODS: 50 pairs of cancer tissues and para-cancerous tissues of patients with bladder cancer were collected. RT-PCR method was used to detect the expression of CRIM1 and miR-182. The association between circRNA CRIM1 and clinical data was analyzed. qPCR was used to measure the expression of circRNA CRIM1 and miR-182 in bladder cancer cell UMUC3 and endothelial cell line HUVEC. CRIM1 genes and miR-182 in UMUC3 cell lines were overexpressed and silenced, respectively, to investigate their effects on invasion and migration of bladder cancer, and to detect the changes of miR182/Foxo3a expression. The association between circRNA CRIM1 and miR182/Foxo3a was determined by bioinformatics analysis. RESULTS: The results showed that there was a significant association between the expression of circRNA CRIM1 and distal migration. The expression of CRIM1 in adjacent tissues was significantly down-regulated and negatively correlated with distal migration. The overexpression of circRNA CRIM1 reduced migration and invasion processes in bladder cancer cells. After circRNA CRIM1 was overexpressed, the miR-182 was significantly down-regulated. The expression levels of Foxo3a mRNA and proteins were up-regulated after miR-182 silencing of bladder cancer cell line UMUC3. miR-182 silencing inhibited invasion and migration of cancer cells to some extent. In bladder cancer cells and tissues, CRIM1 and Foxo3a were significantly down-regulated, miR-182 was significantly up-regulated. CONCLUSION: circRNA CRIM1 regulated the migration and invasion of bladder cancer by targeting the miR182/Foxo3a axis.

[Analysis of low-dose computed tomography compliance and related factors among high-risk population of lung cancer in three provinces participating in the cancer screening program in urban China].

Objective: To analyze the compliance and related factors of low-dose computed tomography (LDCT) screening among the high-risk population of lung cancer in three provinces participating in the cancer early diagnosis and early treatment program in urban areas of China. Methods: From October 2017 to October 2018, 17 983 people aged between 40 and 74 years old at high risk of lung cancer were recruited from Zhejiang, Anhui and Liaoning provinces. The basic demographic characteristics, living habits, history of the disease and family history of cancer were collected by using a cancer risk assessment questionnaire, and the data of participants examined by LDCT were obtained from the hospitals participating in the program. The screening compliance was quantified by the screening participation rate, and it was calculated as the proportion of participants completing LDCT scan among high-risk population. The related factors of LDCT screening compliance were analyzed by using a multivariate logistic regression model. Results: The age of 17 983 participants was (56.52±8.22) years old. Males accounted for 51.9% (N=9 332), and 69.5% (N=12 495) had ever smoked, including former smokers and current smokers. A total of 6 269 participants were screened by LDCT, and the screening participation rate was 34.86%. The results of multivariate logistic regression analysis showed that the age group of 50 to 69 years old, female, passive smokers, alcohol consumption, family history of lung cancer and history of chronic respiratory diseases were more likely to be screened by LDCT, while the compliance of LDCT screening in current smokers was low. Conclusions: The LDCT screening compliance of the high-risk population of lung cancer in urban areas of China still needs to be improved. Age, sex, smoking, drinking, family history of lung cancer and history of chronic respiratory disease are associated with screening compliance.

Long non-coding RNA OR3A4 facilitates cell proliferation and migration in colorectal cancer through the Wnt/ß-catenin signaling pathway.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long non-coding RNA OR3A4 facilitates cell proliferation and migration in colorectal cancer through the Wnt/ß-catenin signaling pathway, by W. Sun, G.-R. Chen, J. Wang, X.-Y. Yu, X.-F. Hao, M.-Y. Hu, published in Eur Rev Med Pharmacol Sci 2020; 24 (10): 5360-5366-DOI: 10.26355/eurrev_202005_21319-PMID: 32495870" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21319.

[Research advances in the relationship of dietary factors and prostate cancer risk].

Prostate cancer is the second most common malignancy in men worldwide. An increasing trend for prostate cancer incidence was observed in China. Enormous studies have been conducted to investigate the association between dietary factors and prostate cancer, however conflicted results were obtained. Red meat, processed meat, and dairy products consumption were reported to be associated with the increased prostate cancer risk, while tomatoes, soybeans and green tea might reduce the risk of prostate cancer occurance. However, no consensus could be reached without strong evidence. Furthermore, further studies are needed to investigate the association between vitamin and mineral supplements and prostate cancer risk. Some studies reported that men with higher dietary inflammatory index scores increased prostate cancer risk. There may be a long susceptible period when dietary factors affect prostate cancer risk, which poses challenges for collecting exposure and the follow-up. Measure bias and detection bias are the main reasons which impair the authenticity of studies on the relationship of dietary factors and prostate cancer risk. Researchers should apply various methods to measure participants' dietary consumption levels and ascertain essential outcomes, such as prostate cancer death. This article reviews updated epidemiological evidences on the association of dietary factors and prostate cancer, aims to benefit future nutritional epidemiology studies focus on the prostate cancer prevention.

[Metabolic syndrome components and breast cancer risk in Chinese females: a population based prospective study].

Objective: To investigate the relationship between metabolic syndrome (MS) and the risk of breast cancer in Chinese females. Methods: From May 2006 to December 2015, based on the Kailuan Women's Dynamic Cohort,a total of 25 618 female employees and retirees of the Kailuan Group were included and followed. Questionnaire surveys, physical measurements and laboratory tests were used to collect baseline sociodemographic characteristics, height, weight, blood glucose, blood lipids, blood pressure, tumor incidence and outcome information. Cox proportional hazards regression models were used to analyze the relationship between MS and its components (body mass index, blood pressure, blood glucose and blood lipid) and the risk of breast cancer in females. Results: The age of 25 618 women was (47.65±12.02) years old and median follow-up time was 8.78 years; 235 new cases of breast cancer were detected, and the incidence density was 113.19/100 000 person-years. After adjusting for age, education, income, smoking status, drinking status and other factors, people who were overweight or obese had a higher risk of breast cancer, with HR (95%CI) about 1.47 (1.12-1.93), than those with normal body mass index. Compared with those without MS abnormal components, women with two MS abnormal components had an increased risk of breast cancer (HR=1.70, 95%CI: 1.16-2.50). With the increase of the number of MS abnormal components, the risk of breast cancer increased gradually (Ptrend value<0.05). Conclusion: Overweight/obesity and the number of abnormal components of MS can increase the risk of breast cancer in women.

Circ_0005276 aggravates the development of epithelial ovarian cancer by targeting ADAM9.

OBJECTIVE: Our purpose was to assess the relationship between circ_0005276 and clinical features of epithelial ovarian cancer (EOC), and to illustrate the regulatory effect of circ_0005276 on migratory potential in EOC cells. PATIENTS AND METHODS: EOC tissues and adjacent normal ones were collected from 49 EOC patients. Relative levels of circ_0005276 and ADAM9 in EOC tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between circ_0005276 and clinical features of EOC patients was analyzed. Moreover, migratory potentials of CAOV3 and SKOV3 cells affected by circ_0005276 were examined by transwell and wound healing assay. Regulatory effects of circ_0005276/ADAM9 feedback loop on the development of EOC were finally detected by Luciferase assay and rescue experiments. RESULTS: It was found that circ_0005276 was upregulated in EOC tissues and its level was positively linked to rates of lymphatic metastasis and distant metastasis in EOC patients. Survival analysis showed worse OS and DFS in EOC patients expressing a high level of circ_0005276 than those with a low level. Besides, knockdown of circ_0005276 attenuated migratory potentials in EOC cells. ADAM9 was verified to be the target gene binding circ_0005276, and its level was positively regulated by circ_0005276. Notably, circ_0005276 aggravated the development of EOC by targeting ADAM9. CONCLUSIONS: Circ_0005276 is highly expressed in EOC tissues, and its level is positively linked to metastasis. Serving as an unfavorable gene in the prognosis of EOC, circ_0005276 aggravates the development of EOC by upregulating ADAM9.

[Clinical characteristics and prognosis of intraductal papillary mucinous neoplasm of the biliary tract].

Objective: To study the clinical features, diagnosis, surgery treatment and prognosis of intraductal papillary mucinous neoplasm of the biliary tract (IPMN-B). Methods: The data of 16 patients with IPMN-B admitted to The First Hospital of Jilin University and Xi'an Third Hospital from January 2014 to January 2018 were retrospectively analyzed. Kaplan-Meier method was used to conduct the survival analysis. These patients included 10 males and 6 females, the median age was 57 years. Results: Clinical manifestations were mainly jaundice (11 cases), upper abdominal pain (12 cases) and hyperpyretic chills (4 cases), combined with bile duct stones (14 cases) and hepatic lobe atrophy (2 cases). The average size of the tumor was (2.6±0.7) cm. All of 16 cases were diagnosed as IPMN-B, including 5 cases of invasive carcinoma (4 cases were perineural invasion) without vascular invasion and 6 cases of non-invasion carcinoma. The pathological type included 8 cases of pancreaticobiliary duct type, 5 cases of gastric type, 2 cases of intestinal type and 1 case of eosinophils type. Laboratory tests showed abnormal liver function (12 cases), increased direct bilirubin (9 cases), increased carbohydrate antigen199 (CA199, 8 cases) and carcinoembryonic antigen (CEA, 4 cases). The enhanced CT detection showed 9 cases of intrabile duct mass and 14 cases of bile duct dilatation. Surgical resection is the main treatment method, including 2 cases of partial resection of liver, 12 cases of bile duct mass resection combined with choledochojejunostomy and 2 cases of pancreatoduodenectomy, all of whom achieved R0 resection. Fifteen patients were followed up and 4 died during the period. The median postoperative progression free survival was 31 months (95% CI: 33-47 months), and the recurrence rate at 1 year, 2-years and 3-years were 6.7%, 40.0% and 73.3%, respectively. The median overall survival was 35 months (95% CI: 23-47 months), and the 1 year, 2-years, and 3-years cumulative survival rates were 100%, 80.0%, and 53.3%, respectively. Conclusions: IPMN-B is a rare tumor of biliary tract system, which is difficult to be diagnosed early. The main treatment is surgical resection, which can achieve a good prognosis.

The expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells.

OBJECTIVE: To investigate the expressions of miR-151a-5p and miR-23b in lung cancer tissues and their effects on the biological functions of lung cancer A549 cells. PATIENTS AND METHODS: Samples of lung cancer tissue (55 cases) and pericarcinomatous tissue (55 cases) were collected in thoracic surgery in our hospital from May 2017 to November 2018. The expression levels of miR-151a-5p and miR-23b in lung cancer tissues and pericarcinomatous tissues were detected by RT-PCR. Lung cancer cells A549 were transfected. Before transfection, the cells were divided into a negative control group (NC group, transfected with miRNA NC), a group transfected with miR-151a-5p inhibitor and a group transfected with miR-23b inhibitor. MTS Cell Proliferation Colorimetric Assay Kit (CCK8) was used to detect cell proliferation and draw the growth curve. Transwell chamber was used to detect the invasion ability in vitro, and BD flow cytometry was used to detect apoptosis in each group. RESULTS: The expression levels of miR-151a-5p and miR-23b in lung cancer tissues were significantly higher than those in pericarcinomatous tissues (p<0.001). After 48 h to 72 h, the cell growth of both the miR-151a-5p inhibitor group and the miR-23b inhibitor group was significantly lower than that of the NC group (p<0.001). The numbers of invasion of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly lower than that of NC group (p<0.00). The apoptosis rates of miR-151a-5p inhibitor group and miR-23b inhibitor group were significantly higher than that of NC group (p<0.001). CONCLUSIONS: Both miR-151a-5p and miR-23b are highly expressed in lung cancer, and the inhibition of miR-151a-5p and miR-23b can restrain the proliferation, invasion and migration of lung cancer A549 cells, thereby promoting the apoptosis of lung cancer A549 cells.

Long non-coding RNA OR3A4 facilitates cell proliferation and migration in colorectal cancer through the Wnt/ß-catenin signaling pathway.

OBJECTIVE: Colorectal cancer (CRC) remains one of the most ordinary cancers worldwide. Recently, researches have suggested the important role of long noncoding RNAs (lncRNAs) in the progression of tumorigenesis. This study aims to identify how lncRNA OR3A4 functions in the development of CRC. PATIENTS AND METHODS: OR3A4 expressions in 54 paired CRC tissues and CRC cell lines were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Moreover, the in vitro functions of OR3A4 in CRC cells were identified by performing proliferation assay, wound healing assay, and transwell assay. Besides, the underlying mechanism of OR3A4 in CRC development was explored through Western blot and RT-qPCR. RESULTS: OR3A4 expression was significantly higher in CRC tissues than adjacent normal ones. Cell proliferation, migration, and CRC were inhibited after OR3A4 was knocked down in vitro, which were promoted after upregulation of OR3A4. Moreover, OR3A4 could activate the Wnt/ß-catenin pathway, thus influencing phenotypes of CRC cells. CONCLUSIONS: OR3A4 enhances CRC cell proliferation and migration by activating the Wnt/ß-catenin signaling pathway.

[A multicenter cross-sectional study on chronic critical illness and surgery-related chronic critical illness in China].

Objective: To understand the prevalence, diagnosis and treatment of chronic critical illness (CCI) in China. Methods: The clinical data of 472 adult patients admitted to ICU in 53 hospitals, including basic information, disease-related data, nutrition program, etc., were collected on May 10, 2019, by means of multi-center cross-sectional study. If surgical intervention was needed or the occurrence of the disease was directly related to the surgery, ICU patients were regarded as surgical ICU cases (n=211). In this study, the diagnostic criteria for CCI were: (1) admission to ICU >14 days;(2) combined with persistent organ dysfunction. The prevalence,distribution and treatment of CCI and surgery-related CCI were recorded and analyzed. The Mann-Whitney U test, chi-square test or Fisher exact test were used for comparative analysis. Results: Among the 472 ICU patients from 53 hospitals, 326 were male (69.1%) and 146 were female (30.9%). The prevalence of CCI was 30.7% (145/472). Among 211 surgery-related ICU patients, 57 developed CCI with a prevalence of 27.0%. As compared to non-CCI patients, higher APACHE II score [median (IQR) 13.5 (10.0, 18.3) vs. 11.0 (7.0, 16.0), U=2970.000, P=0.007], higher Charlson comorbidity index [median (IQR) 4.0 (2.0, 7.0) vs. 3.0 (1.0, 5.0), U= 3570.000, P=0.036] and higher ratio of breath dysfunction [68.4% (39/57) vs. 48.1% (74/154), χ(2)=6.939, P=0.008] and renal dysfunction [42.1% (24/57) vs. 18.2% (28/154), χ(2)=12.821, P<0.001] were found in surgery-related CCI patients. While SOFA score, Glasgow coma score and other visceral function were not significantly different between surgery-related CCI and non-CCI patients (all P>0.05). NUTRIC score showed that surgery-related CCI patients had higher nutritional risk [43.9% (25/57) vs. 26.6%(41/154), U=5.750, P=0.016] and higher ratio of mechanical ventilation [66.7% (38/57) vs. 52.3% (79/154), χ(2)=3.977, P=0.046] than non-CCI patients. On the survey day, the daily caloric requirements of 50.2% (106/211) of surgery-related ICU patients were calculated according to the standard adult caloric intake index (104.6 to 125.5 kJ·kg(-1)·d(-1), 1 kJ=0.239 kcal), and the daily caloric requirements of 46.4% (98/211) of patients were calculated by physicians according to the severity of the patient's condition. 60.2% (127/211) of nutritional support therapy was enteral nutrition (including a combination of enteral and parenteral nutrition), while the remaining patients received parenteral nutrition (24.6%, 52/211), simple glucose infusion (9.0%, 19/211), or oral diet (6.2%, 13/211). The target calorie of CCI group was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie intake accounted for 0.98 (0.80, 1.00) of the target calory. In the non-CCI group, the target calorie was 104.6 (87.9, 125.5) kJ·kg(-1)·d(-1), and the actual calorie consumed accounted for 0.91 (0.66, 1.00) of the target calorie. There was no statistically significant difference between two groups (P=0.248, P=0.150). Conclusion: The prevalence of CCI and surgery-related CCI in ICU is high, along with severe complications, respiratory and renal dysfunction and mechanical ventilation. Surgical patients admitted to ICU are at high nutritional risk, and active and correct nutritional support is essential for such patients.

TATDN1 promotes the development and progression of breast cancer by targeting microRNA-140-3p.

OBJECTIVE: To explore whether long non-coding RNA (lncRNA) TATDN1 can promote the proliferation and cell cycle progression of breast cancer cells by adsorbing microRNA-140-3p, thus participating in the development of breast cancer (BCa). PATIENTS AND METHODS: Expressions of TATDN1 and microRNA-140-3p in BCa tissues and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Meanwhile, TATDN1 expression in BCa cell lines was detected as well. Regulatory effects of TATDN1 and microRNA-140-3p on proliferation and cell cycle progression of BCa cells were evaluated by Cell Counting Kit-8 (CCK-8) and flow cytometry, respectively. The binding relationship of microRNA-140-3p to NOVA1 and TATDN1 was examined by dual-luciferase reporter gene assay. Finally, rescue experiments were conducted to explore whether TATDN1 can regulate NOVA1 expression by adsorbing microRNA-140-3p to exert its biological function in BCa. RESULTS: TATDN1 was highly expressed in BCa tissues and cell lines. Upregulation of TATDN1 promoted the proliferative potential and cell cycle progression of MCF-7 and MDA-MB-231 cells. Dual-luciferase reporter gene assay indicated that TATDN1 could bind to microRNA-140-3p, which was lowly expressed in BCa. Overexpression of microRNA-140-3p inhibited the proliferative potential and cell cycle progression of MCF-7 and MDA-MB-231 cells. Moreover, microRNA-140-3p partially inhibited the role of TATDN1 in regulating cellular behaviors of BCa cells. NOVA1 was predicted to be the target gene of microRNA-140-3p. Overexpression of NOVA1 partially abolished the inhibitory effects of microRNA-140-3p on proliferation and cell cycle progression of MCF-7 and MDA-MB-231 cells. CONCLUSIONS: TATDN1 promotes the proliferative potential and cell cycle progression of BCa cells through adsorbing microRNA-140-3p to upregulate NOVA1 expression.

HSP20-mediated cardiomyocyte exosomes improve cardiac function in mice with myocardial infarction by activating Akt signaling pathway.

OBJECTIVE: To explore the role of heat shock protein 20 (HSP20)-mediated cardiomyocyte exosomes in the cardiac function in mice with myocardial infarction via the activation of the protein kinase B (Akt) signaling pathway. MATERIALS AND METHODS: A total of 30 mice were enrolled to establish the model of myocardial infarction. Next, these mice were divided into three groups, namely Blank group (healthy mice), Model group (mouse models of myocardial infarction), and HSP20 group (mouse models of myocardial infarction transfected with lentivirus to overexpress HSP20). After that, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining assay was performed to detect myocardial apoptosis. Reactive oxygen species (ROS) accumulation in myocardial tissues was determined via dihydroethidium (DHE) staining assay. Western blotting was employed to analyze the expression level of Akt. The expression levels of inflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin 1 beta (IL-1ß) in HSP20-mediated cardiomyocyte exosomes were measured through quantitative real time polymerase chain reaction (qRT-PCR). RESULTS: Compared with that in Blank group, the number of cardiomyocyte exosomes was increased in Model group and HSP20 group under anoxic conditions (p<0.05). The results of quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) proved that the HSP20 messenger ribonucleic acid (mRNA) expression in mediated cardiomyocyte exosomes was significantly lower in Model group than that in Blank group (p<0.05), while in HSP20 group, it was overtly higher than that in Model group but clearly lowered compared with that in Blank group (p<0.05). The protein expression of Akt in cardiomyocyte exosomes was evidently decreased in Model group compared with that in Blank group (p<0.05), while it was notably increased in HSP20 group compared with that in Model group (p<0.05). In comparison with Blank group, Model group had significantly elevated mRNA expression levels of TNF-α and IL-1ß. The mRNA expression levels of TNF-α and IL-1ß in HSP20 group were remarkably lower than those in Model group (p<0.05). The results of TUNEL assay revealed that the overexpression of HSP20 affected myocardial apoptosis. The myocardial apoptosis index in Model group [(38.42±2.52) %] was higher than that in Blank group [(9.74±1.21) %], HSP20 group had a significantly decreased myocardial apoptosis index [(22.36±2.13) %] in comparison with Model group (p<0.05). In accordance with DHE staining comparison, the accumulation of ROS in myocardial tissues in Model group was significantly higher than that in Blank group (p<0.05) and HSP20 group (p<0.05). CONCLUSIONS: We demonstrated that HSP20-mediated cardiomyocyte exosomes activate the AKT signaling pathway, repress TNF-α and IL-1ß factors, and alleviate myocardial infarction.

[The prognostic significance of dynamic monitoring of minimal residual disease (MRD) status in patients with newly-diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of kinetic changes in minimal residual disease (MRD) status, as well as its relationship with risk stratification, therapeutic response and treatment in patients with newly-diagnosed multiple myeloma (MM) . Methods: A total of 135 patients with newly-diagnosed MM were screened, and 105 patients who achieved VGPR or more as the best responses were included into this study. The MRD status was determined by multiparameter flow cytometry (MFC) at multiple intervals after two cycles of treatment until clinical relapse, death, or last follow-up. The statistical methods included Kaplan-Meier analysis, Cox regression, etc. Results: ①In all 135 patients, 57.8% (78/135) patients achieved MRD negativity (MRD(-)) after treatment. In 105 patients who achieved VGPR and thus included in this study, the MRD(-) rate was 72.4% (76/105) , with a median interval of 3 months from starting treatment to achievement of MRD(-) status. ②The 2-year PFS rate of patients with MRD(-) status was significantly higher than that of MRD(+) status (62.2% vs 41.3%, P=0.001) , while MRD persistence (MRD(+)) was an independent factor for poor prognosis (multivariate analysis for PFS: P=0.044, HR=3.039, 95%CI 1.029-8.974) . ③Loss of MRD(-) status (i.e., MRD reappearance) showed inferior outcomes compared with MRD sustained negative ones, the PFS was 18 months versus not reach (P<0.001) and the OS was not reach for both (P=0.002) . ④The 2-year PFS and OS rates of patients with duration of MRD(-)status≥12 months were significantly higher than those of the control group (PFS: 77.7% vs 36.7%, P<0.001; OS: 96.4% vs 57.9%, P<0.001 respectively) . Duration of MRD(-) status was associated with a marked reduction in risk of relapse or death (univariate analysis for PFS: P<0.001, HR=0.865, 95%CI 0.815-0.918; for OS: P=0.001, HR=0.850, 95%CI 0.741-0.915 respectively) . ⑤Moreover, even in patients carrying high-risk cytogenetic abnormalities (CA) or ineligible for ASCT, MRD negativity remained its prognostic value to predict PFS (high-risk CA medianPFS: not reach vs 19 months, P=0.006; ineligible for ASCT medianPFS: not reach vs 25 months, P=0.052 respectively) . ⑥Last, treatment with the bortezomib-based regimens contributed to prolonged MRD(-) duration (median MRD(-) duratio: 25 months vs 10 months, P=0.034) . Conclusion: Our findings supported MRD(+) status as an independent poor prognostic factor in MM patients, which implicated that duration of MRD(-) status also played a significant role in evaluation of prognosis, while loss of MRD(-)status might serve as an early biomarker for relapse. Therefore, monitoring of MRD kinetics might more precisely predict prognosis, as well as guide treatment decision, especially for when to start retreatment in relapsed patients.

[Effect of 1q21 amplification on bortezomib therapeutic response and prognosis of newly diagnosed multiple myeloma patients].

Objective: To investigate the effect of 1q21 amplification (1q) on the therapeutic response and prognosis of bortezomib(Btz) in the treatment of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 180 newly diagnosed MM were included for analyses of clinical characteristics, cytogenetics, objective response rate (ORR), progression-free survival (PFS) and overall survival (OS), retrospectively. Gene expression profiling (GEP) was analyzed using publicly available R2 platform. Results: ① In 180 patients, 1q was found in 51.1% cases. Of them, 174 patients had complete follow-up data, including 88 cases with 1q and 86 without 1q (non-1q). ②Incidence of 1q was positively associated with percentage of IGH rearrangement (72.2%, P=0.017) and 1p deletion (1p) (27.8%, P=0.040). ③ The median PFS was 15.0 and 20.3 months for the 1q group and non-1q group, and the median OS was 29.4 and 44.0 months, respectively. Both PFS and OS of 1q group was significantly shorter than those of the non-1q group (P=0.029 and 0.038, respectively). Multivariate analysis further revealed that 1q was an independent prognostic factor for both PFS (HR=1.910, 95% CI 1.105-3.303, P=0.020) and OS (HR=2.353, 95% CI 1.090-5.078, P=0.029). ④ In 91 evaluable cases with 1q, very good partial remission (VGPR) rate was higher after treatment with Btz than those without Btz (62.1% vs 40.0%, P=0.032). Of note, the patients with 1q who received auto-HSCT after induction with Btz had significantly longer PFS than those without auto-HSCT (19 months vs 13 months, P=0.048). ⑤GEP analysis revealed that 1q21 amplification predominantly up-regulated expression of >50% genes within 1q21 region, and also altered expression of 28% genes in chromosome 1 and 10% genes in whole genome, particularly related to DNA repair and cell cycle. Conclusions: 1q is an independent adverse prognostic factor in patients with newly diagnosed MM. It is often associated with 1p deletion and IGH rearrangement. Patients with 1q respond well to Btz-based regimen, but they fail to gain long-term benefit from this treatment itself. However, auto-HSCT following Btz induction might improve survival of patients with 1q, suggesting a potential strategy to treat this high-risk subset of MM. GEP analysis warrants further attention in understanding the mechanisms underlying the high-risk of 1q.

Effect of FGF2 on the activity of SPRYs/DUSP6/ERK signaling pathway in endometrial glandular epithelial cells of endometriosis.

OBJECTIVE: We aimed at exploring the positive feedback loop in eutopic and ectopic endometrial glandular epithelial cells (EuECs and EECs) in endometriosis. MATERIALS AND METHODS: Normal epithelial cells (NECs), EuECs and EECs were treated with fibroblast growth factor (FGF)2, FGF2 neutralizing antibody, mitogen-activated protein kinases (MAPKs) inhibitors U0126 and PD98059. FGF2 protein level was detected by enzyme-linked immunosorbent assay (ELISA). The expressions of FGF2, FGF receptor 1 (FGFR1), extracellular signal-regulated kinase (ERK)1/2/pERK1/2 and Sproutys (SPRYs) (Sprouty1, Sprouty2, Sprouty4) and dual specificity phosphatase 6 (DUSP6) were detected by Western blot. The mRNA levels of FGF2, FGFR1 (FGF receptor 1), SPRYs (Sprouty1, Sprouty2, Sprouty4) and DUSP6 mRNA were detected by RT-PCR. RESULTS: Among treatment groups, the content of FGF2 in EuECs and EECs was significantly higher than that in NECs (p < 0.05). The mRNA and protein levels of FGF2, FGFR1, SPRYs (Sprouty1, Sprouty2, Sprouty4) and DUSP6 in EuECs and EECs were increased after adding FGF2 (p < 0.05), but decreased after adding FGF2 neutralizing antibody, no significant change was found in NECs (p > 0.05). The inhibitory effect of PD9805 on NECs was not significantly different from that of U0126 (p > 0.05); however, the inhibitory effects of PD9805 on EuECs and EECs were significantly lower than those of U0126 (p< 0.05). CONCLUSIONS: The positive feedback loop existed in EuECs and EECs, but maybe not in NECs. The results may provide the guideline to treat endometriosis patients.

Effect of tobacco smoke on hydrogen sulfide-induced rat thoracic aorta relaxation.

Levels of hydrogen sulfide (H2S), a gaseous signaling molecule, are reduced in the serum of individuals who smoke. We hypothesized that tobacco smoke influenced smooth muscle relaxation by decreasing H2S levels and this effect could also influence expression of cystathionine γ-lyase (CSE) and sulfonylurea receptor-2 (SUR-2). The aim of this study was to explore the effect of tobacco smoke on H2S-mediated rat thoracic aorta relaxation and its possible mechanism. Thirty-two Sprague-Dawley rats were divided into four groups: control (C) group, short-term smoker (SS) group, mid-term smoker (MS) group, and long-term smoker (LS) group. H2S concentrations in serum, action of H2S on rat aortic vascular relaxation, and expression of CSE and SUR-2 in thoracic aortic smooth muscle were measured. Although there was no significant difference in H2S between the C and the SS groups, concentration of H2S was significantly reduced in both the LS and MS groups compared to control (P<0.01). Furthermore, H2S was significantly lower in the LS than in the MS group (P<0.05). Rat aortic vascular relaxation was lower in all three treatment groups compared to the control, with the most significant decrease observed in the LS group (P<0.05 compared to the MS group). Expression of CSE and SUR-2 was reduced in the LS and MS groups compared to control (P<0.05), with the lowest levels observed in the LS group (P<0.05). Therefore, tobacco smoke reduced expression of CSE and SUR-2 in rat thoracic aorta, which may inhibit H2S production and vascular dilation.