Objective To investigate the effects on anti-expression of Osteopontin (OPN) by an antisense oligodeoxynucleotide (ASODN) targeting to low free energy region of OPN mRNA and its effects on the proliferation and apoptosis of human breast carcinoma cell line MCF-7. Methods Designing and synthesizing an ASODN based on minimum free energy algorithm in vitro,which targets to the low free energy region of OPN mRNA. Transfecting it into breast carcinoma cell line MCF-7 which expresses OPN in high level. The cell proliferation-inhibitory rate was determined by MTT method;The morphologic change was observed through transmission electron microscope (TEM);The OPN mRNA expression level was checked by RT-PCR method;Cell cycle and apoptosis rate were detected by flow cytometry (FCM) after transfection respectively. Results OPN ASODN inhibited the proliferation of the cells by a time and concentration dependent manner (P

AIM: To explore the effects of exendin-4 (EX-4) on endoplasmic reticulum stress (ERS)-mediated insulin resistance in the 3T3-L1 adipocytes.METHODS: In vitro 3T3-L1 pre-adipocytes were differentiated into adipocytes, and the cells were treated with tunicamycin (TM), tauroursodeoxycholic acid (TUDCA) or EX-4, respectively.The cell viability was measured by MTT assay.The glucose consumption was determined by glucose oxidase assay to evaluate insulin sensitivity of the 3T3-L1 adipocytes with different interventions.The protein levels of p-Akt, Akt and endoplasmic reticulum stress markers, including inositol requiring enzyme-1 (IRE1), p-IRE1, JNK, p-JNK, protein kinase R-like endoplasmic reticulum kinase (PERK), p-PERK, eukaryotic initation factor 2 alpha (eIF2a), p-eIF2a, activating transcription factor-6(ATF-6) were detected by Western blot.RESULTS: The insulin-stimulated glucose consumption and the protein level of p-Akt were inhibited by TM at 5 mg/L for 5 h (P<0.05), while they were increased when the cells were treated with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The effects above induced by TM (5 mg/L for 5 h) were also blunted by pretreating with TUDCA at 1 mmol/L or EX-4 at 100 nmol/L for 24 h (P<0.05).The protein levels of ERS markers such as p-IRE1, p-JNK, p-PERK, p-eIF2a and ATF-6 were significantly increased by treating with TM at 5 mg/L for 5 h, whereas 24 h pre-treatment with TUDCA or Ex-4 alleviated the ERS of the 3T3-L1 adipocytes induced by TM.The expression of total IRE1, JNK, PERK and eIF2a was not changed in different groups.CONCLUSION: Exendin-4 improves endoplasmic reticulum stress mediated insulin resistance in 3T3-L1 adipocytes.

OBJECTIVETo explore the impact of isolated diastolic hypertension (IDH) on new-onset cardio-cerebral vascular diseases (CVD).

METHODSThis cohort study involved 101 510 participants who were employees of the Kailuan Group-a state-run coal mining company, in 2006 and 2007. Among them, 6 780 subjects were diagnosed with IDH, 35 448 subjects were diagnosed with high-normal blood pressure and 19 460 subjects were diagnosed with normal tension. However, none of them had the history of either cardio-cerebral vascular disease or malignant cancer. Cardio-cerebral vascular events including cerebral infarction, cerebral hemorrhage, acute myocardial infarction were recorded every 6 months during the follow-up (47.1 ± 4.8) period. Multivariable Cox proportional hazards regression models were used to analyze the risk factors of first-ever CVD events.

RESULTS1) There were 675 CVD events occurred during the follow-up period. The incidence rates of CVD events (1.7% vs. 0.9%), cerebral infarction (1.0% vs. 0.6%) and cerebral hemorrhage (0.4% vs. 0.1%) were significantly higher in IDH group than that in the normal tension group (all P < 0.05). 2) After adjustment for other established CVD risk factors, the hazards ratios became 1.67 (95% CI: 1.28-2.17) for total CVD events and 1.59 (95% CI: 1.12-2.27) for cerebral infarction and 2.67 (95% CI: 1.54-4.65) for cerebral hemorrhage in the IDH group. 3). In stratified analysis on age, after adjustment for other established CVD risk factors, the hazards ratio was 2.22 (95% CI: 1.41-3.50) for cerebral infarction in lower 60 years old group, while the it was 7.27 (95% CI: 2.58-20.42) for cerebral hemorrhage in groups older than 60 years of age.

CONCLUSIONIDH was the independent risk factor for the total cardio-cerebral vascular events, on both cerebral infarction and cerebral hemorrhage. The predicted values of IDH for different CVD events were diverse on different age groups.

Adult ; Cardiovascular Diseases ; epidemiology ; Female ; Follow-Up Studies ; Humans ; Hypertension ; complications ; Male ; Middle Aged ; Proportional Hazards Models ; Risk Factors

OBJECTIVETo explore the prevalence of isolated diastolic hypertension and associated cardiovascular risk and blood pressure changes during follow up.

METHODSThis cohort study screened 101 510 participants who were employees of the Kailuan Group, a state-run coal mining company in 2006 and 2007. Among them, 6 778 subjects were diagnosed with isolated diastolic hypertension (IDH). IDH subjects without history of cardiovascular disease and not treated with antihypertensive drugs were included in this analysis. Participants without health examination between 2008 to 2009 or 2010 to 2011 were excluded. A total of 4 600 participants were included in the final analysis. At the end of the third health examination, the conversion rate of different blood pressure turnover was calculated after standardizing age and gender according to demographic data of China in 2006. Multivariate logistic regression analysis was applied to analyze the risk factors of blood pressure turnover in IDH population.

RESULTS(1) Participants were followed up for (4.03 ± 0.26) years and the rates of turnover from IDH to normotension, isolated systolic hypertension (ISH) and systolic diastolic hypertension (SDH) were 51.4%, 3.5%, 18.3%, respectively (45.6%, 3.6%, 22.0% in male, 57.4%, 3.3%, 14.7% in female). (2) Multivariate logistic regression analysis showed that low baseline age, low diastolic pressure, low body mass index, low uric acid, physical exercise and low alcohol intake were associated with turnover from IDH to normotension; the risk factors of turnover from IDH to ISH were older age at baseline, higher systolic pressure and higher sensitivity C-reactive protein; the risk factors of turnover from IDH to SDH were older baseline age, high systolic pressure and excessive salt intake.

CONCLUSIONSUntreated subjects with IDH can transform from IDH to normotension,ISH, SDH, and the rate of turnover from IDH to normotension is higher than others during follow up. Aging, higher systolic pressure, higher sensitivity C-reactive protein and excessive salt intake are risk factors for IDH subjects to suffer from ISH and SDH.

Adult ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Hypertension ; epidemiology ; Logistic Models ; Male ; Middle Aged ; Prevalence ; Prognosis ; Risk Factors

Objective To simulate the biomechanical characteristics of pelvic-ligament-muscle during vaginal delivery and rest, and to explore the injury of levator ani muscles during vaginal delivery, pelvic organ prolapse and stress urinary incontinence. Methods The three-dimensional (3D) nonlinear finite element model of pelvis-ligament-muscle was established to calculate the stress and strain distributions and injury of levator ani muscles under different abdominal pressures and loads. The stress and strain distributions as well as damage of type I, Ⅱ, Ⅲ stress urinary incontinence and pelvic organ prolapse were also calculated. Results The highest equivalent stresses of levator ani were 14, 29, 43, 86, 144, 230 kPa, respectively, when the abdominal pressure was 1 kPa under the load of 3, 5, 8 kPa and the abdominal pressure was 1.5 kPa under the load of 3, 5, 8 kPa. The stresses of type I, Ⅱ, Ⅲ stress urinary incontinence and pelvic organ prolapse were 1.69, 1.01, 0.70, 1.58 MPa. Conclusions Vaginal delivery would result in the damage to the puborectalis and the middle of the pubococcipital muscle, which was consistent with the damage of the anal levator muscle with pelvic floor dysfunction. This study uses scientific method to find out the exact location of pelvic floor injury during vaginal delivery, which can provide references for clinicians to prevent pelvic floor disease and formulate post natal rehabilitation training.

Objective:To investigate the clinical efficacy and prognostic influencing factors of radical surgery for duodenal gastrointestinal stromal tumor (GIST).Methods:The retrospective cohort study was conducted. The clinicopathological data of 741 duodenal GIST patients who under-went radical surgery in 17 medical centers, including 121 cases in Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine, 121 cases in Chinese PLA General Hospital, 116 cases in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 77 cases in Fudan University Shanghai Cancer Center, 77 cases in West China Hospital, Sichuan University, 31 cases in Guangdong Provincial People′s Hospital, 24 cases in Fujian Cancer Hospital, 22 cases in Fujian Medical University Union Hospital, 25 cases in Shengjing Hospital of China Medical University, 19 cases in Xiangya Hospital, Central South University, 23 cases in Zhejiang Cancer Hospital, 17 cases in Liaoning Cancer Hospital＆Institute, 17 cases in the First Affiliated Hospital of Xiamen University, 15 cases in Sun Yat-sen University Cancer Center, 14 cases in the First Affiliated Hospital of Nanjing Medical University, 14 cases in Zhongshan Hospital Affiliated to Xiamen University and 8 cases in General Hospital of Chinese People′s Liberation Army Air Force, from January 2010 to April 2020 were collected. There were 346 males and 395 females, aged 55(range, 17?86)years. Observation indicators: (1) neoadjuvant treatment; (2) surgical and postoperative situations; (3) follow-up; (4) stratified analysis. Follow-up was conducted using outpatient examination or telephone interview. Patients were followed up once every 3?6 months during neoadjuvant therapy and once every 6?12 months after radical surgery to detect tumor recurrence and survival of patient up to April 2022. Measurement data with normal distribution were represented as Mean± SD. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using chi-square test or Fisher exact probability. The Kaplan-Meier method was used to draw survival curves and calculate survival rates. Log-rank test was used for survival analysis. The COX regression model was used for univariate and multivariate analyses. Propensity score matching was done by the 1∶1 nearest neighbor matching method, and the matching tolerance was 0.02. Results:(1) Neoadjuvant therapy. Of the 741 patients, 34 cases received neoadjuvant therapy for 8(range, 3?44)months. Cases assessed as partial response, stable disease and progressive disease before the radical surgery of the 34 cases were 21, 9, 4, respectively. The tumor diameter of the 34 patients before the neoadjuvant therapy and before the radical surgery were 8.0(range, 3.0?26.0)cm and 5.3(range, 3.0?18.0)cm, with the regression rate as 31.9%(range, ?166.7% to 58.3%). (2) Surgical and postoperative situations. Of the 741 patients, 34 cases underwent radical surgery after receiving neoadjuvant therapy, and 707 cases underwent radical surgery directly. All the 741 patients underwent radical surgery successfully, in which 633, 102 and 6 cases received open surgery, laparoscopic surgery and endoscopic treatment, respectively. Of the 633 cases receiving open surgery and the 102 cases receiving laparoscopic surgery, cases with surgical resection range as pancreatoduodenectomy (PD) was 238, and cases with surgical resection range as duodenal limited resection, including duodenal wedge resection, distal gastrectomy, segmental duodenal resection, local resection of duodenal tumor or segmental duodenum combined with subtotal gastrectomy, was 497, 226, 55, 204, 12. Of the 741 patients, 131 cases had post-operative complications including 113 cases with grade Ⅰ?Ⅱ complications and 18 cases with ≥ grade Ⅲ complications of the Clavien-Dindo classification. The duration of postoperative hospital stay of the 741 patients was 13(range, 4?120)days. Of the 707 patients receiving direct radical surgery, 371 cases were evaluated as extremely low risk, low risk, medium risk of the modified National Institutes of Health (NIH) risk classification after surgery, and 336 cases were evaluated as high risk in which 205 cases receive postoperative adjuvant imatinib therapy with the treatment time as 24(range, 6?110)months. (3) Follow-up. All the 741 patients were followed up for 58(range, 7?150)months. During the follow-up, 110 patients had tumor recurrence and metastasis. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 741 patients were 100.0%, 98.6%, 94.5% and 98.4%, 90.9%, 84.9%, respectively. The 1-, 3-, 5-year overall survival rates and 1-, 3-, 5-year disease-free survival rates of the 707 patients receiving direct radical surgery were 100.0%, 98.5%, 94.3% and 98.4%, 91.1%, 85.4%, respectively. (4) Stratified analysis. ① Analysis of prognostic factors in patients undergoing radical surgery directly. Results of univariate analysis showed that primary tumor location, tumor diameter, mitotic count, modified NIH risk classification and tumor gene information were related factors affecting the overall survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.43, 0.18, 0.22, 0.06, 0.29, 95% confidence intervals as 0.20?0.93, 0.09?0.35, 0.10?0.50, 0.03?0.12, 0.09?0.95, P<0.05). The primary tumor location, tumor diameter, mitotic count, modified NIH risk classification were related factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=0.65, 0.25, 0.25, 0.10, 95% confidence intervals as 0.41?1.03, 0.17?0.37, 0.15?0.42, 0.07?0.15, P<0.05). Results of multivariate analysis showed that primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation were independent risk factors affecting the overall survival of 365 patients with primary duodenal GIST after removing 342 patients without tumor gene information who underwent direct radical surgery ( hazard ratio=2.85, 2.73, 3.13, 95% confidence intervals as 1.12?7.20, 1.07?6.94, 1.23?7.93, P<0.05). Tumor diameter >5 cm and mitotic count >5/50 high power field were independent risk factors affecting the disease-free survival of 707 patients with primary duodenal GIST who underwent direct radical surgery ( hazard ratio=3.19, 2.98, 95% confidence intervals as 2.05?4.97, 1.99?4.45, P<0.05). ② Effect of postoperative adjuvant therapy on prognosis of high-risk patients of modified NIH risk classification. Of the 336 patients evaluated as high risk of the modified NIH risk classification, the 5-year overall survival rate and 5-year disease-free survival rate were 94.6% and 77.3% in the 205 cases with postoperative adjuvant therapy, versus 83.2% and 64.4% in the 131 cases without postoperative adjuvant therapy, showing significant differences between them ( χ2=8.39, 4.44, P<0.05). Of the 205 patients evaluated as high risk of the modified NIH risk classification who received postoperative adjuvant therapy, there were 106 cases receiving postoperative adjuvant therapy <36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 87.1% and 58.7%, and there were 99 cases receiving post-operative adjuvant therapy ≥36 months, with the 5-year overall survival rate and 5-year disease-free survival rate were 100.0% and 91.5%. There were significant differences in the 5-year overall survival rate and 5-year disease-free survival rate between the 106 patients and the 99 patients ( χ2=13.92, 29.61, P<0.05). ③ Comparison of clinical efficacy of patients with different surgical methods. Before propensity score matching, cases with primary tumor located at bulb, descending, horizontal, ascending segment of duodenum, cases with tumor diameter ≤5 cm and >5 cm were 95, 307, 147, 34, 331, 252, in the 583 patients receiving open surgery with complete clinical data, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery with complete clinical data, showing no significant difference in the primary tumor location ( χ2=0.94, P>0.05), and a significant difference in the tumor diameter ( χ2=17.33, P<0.05) between them. After propensity score matching, the above indicator were 16, 39, 20, 8, 67, 16 in the 83 patients receiving open surgery, versus 15, 46, 17, 5, 67, 16 in the 83 patients receiving laparoscopic surgery, showing no significant difference between them ( χ2=1.54, 0.00, P>0.05). Cases with postoperative complications, cases with grade Ⅰ?Ⅱ complica-tions and ≥grade Ⅲ complications of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 17, 12, 5, 11(range, 5?120)days, 92.0%, 100.0% in the 83 patients receiving open surgery, versus 9, 7, 2, 11(range, 5?41)days, 91.6%, 97.3% in the 83 patients receiving laparoscopic surgery, showing no signi-ficant difference in postoperative complications, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=2.91, Z=3 365.50, χ2=3.02, 1.49, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification between them ( P>0.05). ④ Comparison of clinical efficacy of patients with primary tumor located at the descending segment of duodenum who underwent surgery with different surgical resection scopes. Before propensity score matching, cases with tumor diameter ≤5 cm and >5 cm, cases with tumor located at opposite side of mesangium and mesangium were 71, 85, 28, 128 in the 156 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 92, 41, 120, 13 in the 133 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing significant differences between them ( χ2=16.34, 150.10, P<0.05). After propensity score matching, the above indicator were 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 28, 13, 16, 25 in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference between them ( χ2=0.00, 0.00, P>0.05). Cases with postopera-tive complications, cases with grade Ⅰ?Ⅱ complications and ≥grade Ⅲ compli-cations of the Clavien-Dindo classification, duration of postoperative hospital stay, the 5-year overall survival rate and 5-year disease-free survival rate were 13, 11, 2, 15(range, 9?62)days, 94.2%, 64.3% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent PD with complete clinical data, versus 9, 8, 0, 15(range, 7?40)days, 100.0%, 78.8% in the 41 patients with primary tumor located at the descending segment of duodenum who underwent duodenal limited resection with complete clinical data, showing no significant difference in post-operative complica-tions, the 5-year overall survival rate and 5-year disease-free survival rate ( χ2=0.99, 0.34, 1.86, P>0.05) between them. There was no significant difference in complications of the Clavien-Dindo classification ( P>0.05) and there was a significant difference in duration of postopera-tive hospital stay ( Z=614.50, P<0.05) between them. Conclusions:The clinical efficacy of radical surgery for duodenal GIST are ideal. Primary tumor located at the horizontal segment of duodenum, mitotic count >5/50 high power field, tumor gene KIT exon 9 mutation are independent risk factors affec-ting the overall survival of patients undergoing direct radical surgery and tumor diameter >5 cm and mitotic count >5/50 high power field are independent risk factors affecting the disease-free survival of patients. There is no significant difference in the short-term efficacy and long-term prognosis between patients undergoing open surgery and laparoscopic surgery. For patients with primary tumor located at the descending segment of duodenum, the duration of postoperative hospital stay is longer in patients undergoing PD compared with patients undergoing duodenal limited resection. For patients evaluated as high risk of the modified NIH risk classification, posto-perative adjuvant therapy and treatment time ≥36 months are conducive to improving the prognosis of patients.