[Risk factors and predictors of persistent ectopic pregnancy after interstitial pregnancy surgery].

Objective: To explore the related factors and early predictors of persistent ectopic pregnancy (PEP) in patients with interstitial pregnancy after operation. Methods: The clinical data of patients with interstitial pregnancy who underwent surgery in the Department of Obstetrics and Gynecology of Peking Union Medical College Hospital from January 2013 to August 2021 were collected. Patients were divided into two groups according to whether PEP occurred (8 patients in PEP group and 124 patients in non-PEP group). Using propensity score matching (PSM) analysis, the basic data, surgical methods, the ratio of postoperative to preoperative serum ß-human chorionic gonadotropin (ß-hCG), the duration of when the serum ß-hCG had decreased to normal after the operation were compared and analyzed to find the related factors of PEP after interstitial pregnancy surgery. The sensitivity and specificity of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG in predicting postoperative PEP were evaluated by drawing receiver operating characteristic (ROC) curve. Results: Before PSM, the ages of patients in PEP group and non-PEP group were (30.0±4.0) and (32.4±5.0) years old, respectively, P>0.05. After PSM, 8 PEP patients in the study group and 29 patients in the control group were matched successfully, and the ages of the two groups were (30.0±4.0) and (30.1±3.2) years old, respectively, P>0.05. After PSM, there was no significant difference in gravidity, parity, menopausal days, preoperative ß-hCG level and maximum diameter of lesions, all P>0.05. After PSM, the proportion of patients with maximum diameter ≤ 2.6 cm in PEP group (6/8) was significantly higher than that in control group (31.0%, 9/29), P=0.025. The median (Q1, Q3) of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio was 52.9% (49.9%, 59.7%) in the PEP group, which was significantly higher than 31.5% (23.8%, 39.0%) in the control group (P=0.001); The median (Q1, Q3) of duration of when the serum ß-hCG had decreased to normal after the operation in PEP group was 52.0 (34.8, 92.0) d, which was significantly higher than 24.0 (20.5, 31.0) d in control group (P<0.001). The ROC-Area Under Curve of the ratio of 24-48 hours postoperative ß-hCG to preoperative ß-hCG ratio for predicting postoperative PEP in the two groups was 0.892 (95%CI: 0.725-1.000, P=0.001). The cut-off value for predicting PEP was 48.5%, where the diagnostic sensitivity was 87.5%, the specificity was 93.1%. Conclusions: In the operation of interstitial pregnancy, the maximum diameter of lesion ≤ 2.6 cm is a related factor for postoperative PEP. There was no significant difference in the risk of PEP between cornuotomy and cornectomy. The ratio that 24-48 hours postoperative ß-hCG/preoperative ß-hCG ratio greater than 48.5% was a reference index for predicting postoperative PEP and guiding treatment.

[Clinical analysis of surgical treatment of cornual pregnancy of 109 cases].

Objective: To study the clinical characteristics of cornual pregnancy and compare the effects of various surgical methods on the outcomes. Methods: This was a single-center retrospective study. The clinical records of patients with cornual pregnancy who underwent surgery in Peking Union Medical College Hospital from June 2012 to December 2020 were collected. Surgical interventions included curettage (guided by ultrasound or monitored by laparoscope), and cornuostomy/cornectomy (the surgical approach by laparoscopy or laparotomy). The baseline data, perioperative treatment and whether persistent ectopic pregnancy (PEP) occurred after surgery were collected and analyzed statistically. Results: A total of 109 patients with cornual pregnancy diagnosed by surgical treatment were included in this study, whose average age was (32.9±4.8) years. Among them, the incidence of postoperative PEP was 16.5% (18/109). The risk of PEP in multipara was significantly higher than that in nulliparous women (OR=7.639, 95%CI: 2.063-28.279, P=0.001). The risk of PEP in patients with the maximum diameter of lesion<1.5 cm was significantly higher than that in patients with the maximum diameter of lesion≥1.5 cm (OR=8.600, 95%CI: 2.271-32.571, P=0.002). Among all surgical approaches for cornual pregnancy, the proportion of PEP in curettage under ultrasound monitoring was the highest (56.0%, 14/25), which was higher than that in curettage under laparoscope monitoring (1/10; χ2=6.172，P=0.013); the proportion of PEP in curettage group (42.9%, 15/35) was higher than that in cornuostomy/cornectomy group (4.1%, 3/74; χ2=25.950，P<0.01). Neither salpingectomy in the operation nor the routine use of methotrexate (MTX) in perioperative period could significantly reduce the incidence of PEP (all P>0.05). Conclusions: Among the patients with cornual pregnancy, multipara, the maximum diameter of lesion<1.5 cm and ultrasound-guided curettage are the risk factors of PEP after operation. Cornuostomy or cornectomy is recommended for patients with cornual pregnancy. If the patients would perform the curettage operation, laparoscopic monitoring is recommended. For patients with possible satisfactory operation outcome, it is not recommended to use MTX as a routine preventing measure.

Cigarette smoking and risk of herpes zoster: a population-based cohort study in Taiwan.

The effects of cigarette smoking on the risk of herpes zoster (HZ) infection remain unclear. This study aimed to examine the association between cigarette smoking and HZ. Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of HZ were identified from the Taiwanese National Health Insurance database. Of the 57 641 participants, 3346 developed HZ during the observation period. After controlling for confounders, current smokers had a lower risk of incident HZ than never-smokers (adjusted hazard ratio 0.69; 95% CI 0.62-0.77). There was a trend toward a decreased risk of HZ with increasing numbers of cigarettes per day, years of smoking and cumulative pack-years of smoking among current smokers (Ptrend < 0.001). Former smoking was not associated with risk of HZ. In conclusion, current smoking was significantly associated with a decreased risk of developing HZ.

[Imaging features and clinical analysis of diffuse uterine leiomyomatosis cases].

Objective: To discuss the imaging, clinical features and management of diffuse uterine leiomyomatosis (DUL). Methods: Six cases of DUL confirmed in Peking Union Medical College Hospital from August 2009 to September 2019 were reviewed on their image and clinical data. Retrospective analysis was conducted on their perioperative and postoperative follow-up data. Results: The average age of the first diagnosis of DUL was (27±3) years old. All of the patients complained menorrhagia and three patients suffered moderate to severe anemia. Three patients were diagnosed infertility. Pelvic ultrasound and MRI showed symmetrical enlarged uterus with complete replacement of the myometrium by innumerable, confluent leiomyomas.Four patients were treated with GnRH-a before operation to reduce the volume of myoma and correct anemia. Among the six patients, five had undergone myomectomy because of DUL before visiting Peking Union Medical College Hospital. Three patients underwent open myomectomy. The number of resected myoma was 188-300 and the bleeding volume was 1 200-2 500 ml. Two of them suffered recurrence at 51 and 40 months after operation. One received sirolimus for 20 months without recurrence until now. Other three patients underwent hysterectomy. One patient underwent partial small bowel resection and partial omentum resection because of severe pelvic adhesion during hysterectomy, and the blood loss was 2 000 ml. Conclusions: Pelvic imaging especially MRI is helpful for early recognition and preoperative evaluation for DUL. Fertility preservation is a great challenge for DUL patients. The risk of recurrence after myomectomy is high. Hysterectomy is the last choice to completely cure DUL at present.

Cigarette smoking and risk of rosacea: a nationwide population-based cohort study.

BACKGROUND: Most evidence regarding the relationship between cigarette smoking and risk of rosacea is obtained from cross-sectional or case-control studies. OBJECTIVE: To examine the association between smoking and risk of developing rosacea. METHODS: Participants were collected from four rounds (2001, 2005, 2009 and 2013) of the Taiwan National Health Interview Survey. Incident cases of rosacea were identified from the National Health Insurance database. Cox proportional hazard model was used for the analyses. RESULTS: Of the 59 973 participants, 379 developed rosacea during a mean follow-up of 10.8 years. After adjustment for potential confounders, current smokers had a lower risk of rosacea than never smokers [adjusted hazard ratio (aHR) 0.60; 95% confidence interval (CI) 0.39-0.92]. An increase in smoking intensity was associated with a decreased risk of rosacea among current smokers (Ptrend  = 0.0101). Compared with never smokers, current smokers of >15 cigarettes/day had an aHR of 0.51 (95% CI: 0.26-0.99) for rosacea. For incident rosacea, the aHRs (95% CIs) of current smokers of ≤10 years of smoking and ≤10 pack-years of smoking were 0.44 (0.22-0.88) and 0.51 (0.29-0.89), respectively. Former smoking was not associated with rosacea risk. CONCLUSION: Current smoking was significantly associated with a decreased risk of rosacea.

lncRNA CASC2 suppresses the growth of hemangioma cells by regulating miR-18a-5p/FBXL3 axis.

Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.

Increased risk of major depressive disorder among probands with psoriasis and unaffected siblings: a nationwide population-based study.

BACKGROUND: Previous studies have shown that patients with psoriasis have a higher risk of depression. However, the risk of major depressive disorder (MDD) among unaffected siblings of psoriasis probands remains unknown. This study aimed to investigate the risk of MDD among probands with psoriasis and unaffected siblings. METHODS: We selected subjects from the National Health Insurance Research Database (NHIRD) in Taiwan. Subjects were followed up from 01 January 1996 until a diagnosis of MDD, death or 31 December 2011. The Breslow-Cox model was used to calculate the adjusted relative risk (aRR). RESULTS: This study included 1094 probands with psoriasis, 1202 unaffected siblings and 4808 matched controls. Overall, 11.9% of the psoriasis probands (n = 130) and 2.5% of the unaffected siblings (n = 30) developed MDD, as compared with 1.1% of the controls (n = 52). Compared with controls, probands with psoriasis and unaffected siblings had aRRs of 10.60 [95% confidence interval (CI): 7.73-14.52] and 2.17 (95% CI: 1.44-3.28), respectively, for MDD. CONCLUSIONS: Probands with psoriasis and unaffected siblings have an increased risk of subsequently developing MDD. Further studies are needed to investigate the shared familial mechanisms underlying psoriasis and MDD.

[Establishment and evaluation of an animal model of female pelvic nerve injury].

Objective: To build a stable animal model simulating pelvic nerve injury in female pelvic floor dysfunction. Methods: A total of 55 10-week-old female SD rats weighing (220±15) g were randomly divided into 3 groups: 5 for normal group, 25 for sham operation group (SO), 25 for bilateral pudendal nerve block group (BPNB). Samples of rat anterior vaginal wall were obtained in 3 days, 1 week, 1 month and 3 months after the operation. The number of nerve fibers was counted per high power field under microscope, with UCHL immunohistochemical staining of nerve fibers. RNA was extracted and the expression of RNA related to nerve tissue was tested. Results: The numbers of nerve fibers had no significant difference between the normal group and the sham operation group. The numbers of nerve fibers in anterior vaginal wall of rats in BPNB group, was obviously decreased in 3 days after the operation, reached a minimum value at 1 weeks, and lasting till 3 months. QRT-PCR indicated that the expression of UCHL mRNA in the BPNB group was significantly decreased after 1 week, 1 month and 3 months, while the expression of Nestin was significantly decreased 1 month and 3 months after the operation. Conclusions: Bilateral pudendal nerve block could be used to make rat models of anterior vaginal nerve injury for further exploratory research on pelvic nerve injury theory of pelvic floor dysfunction.

[Safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions].

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion: Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

MicroRNA-375 regulates proliferation and apoptosis of glioma cancer cells by inhibiting CTGF-EGFR signaling pathway.

AIM: To evaluate the correlation between miRNA-375 and cell proliferation and apoptosis in glioma cancer cell. METHODS: Collecting 30 cases of glioma cancer patients and 30 cases of cerebral infarction patients. The miRNA-375 and CTGF protein expressions were evaluated by ISH and IHC methods. In the cell experiment, the U87 cells were divided into 3 groups: NC group (the cells were treated with normal method); BL group (the cells were transfected with empty vector) and miRNA group (the cells were transfected with miRNA-375). The U87 cell proliferation and apoptosis rates and cell cycle of the different groups were measured by MTT and flow cytometry. The relative proteins (CTGF, EGFR, AKT, Erk and P21) expressions were measured by WB assay. RESULTS: The miRNA-375 and CTGF expressions of glioma cancer tissues were significantly different compared with those of no-cancer tissues (p < 0.05, respectively). In the cell experiments, the cell proliferation of miRNA group was significantly decreased compared with that of NC group (p < 0.05); the cell apoptosis and G1 phase rate of miRNA group was significantly decreased compared with NC group (p < 0.05, respectively). Depending on the WB assay, the CTGF, EGFR, AKT, Erk and P21 proteins expressions of miRNA group were significantly different compared with proteins expressions of NC group (p < 0.05, respectively). CONCLUSION: miRNA-375 over-expression suppresses glioma cancer cells development via CTGF-EGFR pathway (Fig. 3, Ref. 30).

[Association between illness and mental status in pregnant women and birth defects].

Objective: To understand the prevalence of birth defects, related diseases and mental status of women during pregnancy in Shaanxi province and to analyse the major risk factors on birth defects and congenital heart disease. Possible association between maternal diseases or mental status and the risk of birth defects, was also explored. Methods: A cross-sectional design was used in this study and stratified multistage random sampling method was used. The whole survey was from Jury 2013 to November 2013. Logistic regression method was used to analyze the association between maternal diseases, mental status during pregnancy and birth defects. Results: The overall prevalence of birth defects was 195.04 per 10 000 in Shaanxi. Among the 29 121 mothers participating in this study, 51.1% developed illness and 6.8% "changed their mental status during pregnancy. After adjusting all the confounding factors, results showed that, histories of cold" , fever, and intrahepatic cholestasis were (OR=1.33, 95%CI: 1.10-1.61, OR=1.54, 95%CI: 1.09-2.16, and OR=32.77, 95%CI:4.08-263.04) respectively, during pregnancy that related to birth defects. Self-reported unstable mental status (OR=1.60, 95%CI: 1.19-2.15) and family friction (OR=2.07, 95%CI: 1.12-3.79) were both related to the birth rates. Histories of cold and fever (OR=1.59, 95%CI: 1.28-1.98; OR=1.43, 95%CI: 1.48-4.00), during early pregnancy, unstable mental status during mid-pregnant period (OR=1.52, 95%CI: 1.05-2.19), unstable mental status during late-pregnant period (OR=1.63, 95%CI: 1.05-2.19) and family friction during late-pregnant period (OR=2.89, 95%CI: 1.16-7.20) were found to be related to birth defects. Compared with those without history of cold, those with the history of cold during first (OR=1.24, 95%CI: 1.02-1.52) and second stages (OR=2.06, 95%CI: 1.30-3.26) of pregnancy were more likely to bear fetus with birth defects. Compared with those without these histories, those with histories of fever (OR=1.49, 95%CI: 1.04-2.13), emotional problem (OR=1.71, 95%CI: 1.19-2.45) and related diseases (OR=2.67, 95%CI: 1.32-5.39) during the first period of pregnancy were more likely to bear fetus with birth defects. Conclusion: The incidence of birth defects in Shaanxi was high. Histories of cold, fever, unstable mental status and family friction during pregnancy, seemed to have increased the risks of bearing child with birth defects.

Effect of IL-1ß, IL-8, and IL-10 polymorphisms on the development of myocardial infarction.

Myocardial infarction (MI) is currently a leading cause of death worldwide, and is caused by various environmental and genetic factors. We therefore conducted a case-control study to investigate the association between polymorphisms in interleukins IL-1ß, IL-8, and IL-10 and MI risk. This study recruited 260 MI patients and 285 control subjects. Genotyping of IL-1ß +3954C/T, IL-8 -251T/A, IL-10 -1082A/G, and IL-10 -819C/T were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. By comparing the risk factors of MI between the case and control groups, we discovered that MI patients were more likely to have smoking and drinking habits, have a history of hypertension and diabetes, have higher triglycerides and low-density lipoprotein cholesterol levels, and a lower high-density lipoprotein cholesterol level (P < 0.05). Unconditional regression analyses showed that subjects carrying the GG genotype of the IL-10 -1082A/G polymorphism were associated with increased risk of MI, and the OR (95%CI) was 2.04 (1.15-3.65). Our study found that the IL-10 -1082A/G polymorphism plays an important role in influencing the development of MI.

Oxymatrine suppresses proliferation and induces apoptosis of hemangioma cells through inhibition of HIF-1a signaling.

Oxymatrine (OMT), a natural quinolizidine alkaloid, has been known to have anti-inflammation, anti-anaphylaxis, and chemopreventive effects on various cancer cells. To clarify the underlying role and molecular mechanisms of OMT in human hemangioma (HA), in the present study, we examined the expression of hypoxia-inducible factor-1a (HIF-1a) and vascular endothelial growth factor (VEGF) in different phases of human HA. After HA derived endothelial cells (HDEC) were pretreated with different concentrations of OMT, cell proliferation, apoptosis, and cycle distribution were evaluated by MTT assay and flow cytometry analysis, respectively. The effects of OMT on expression of HIF-1a signaling were determined by real-time PCR and western blot assays. Our results showed that, the expression of HIF-1a and VEGF was significantly increased in proliferating phase HA, but decreased in involuting phase HA. Moreover, OMT in vitro inhibited proliferative activities and induced cell apoptosis and cycle arrest in G0/G1 phase in HA cells with decreased expression of HIF-1a, VEGF, Bcl-2, and CyclinD1, and increased expression of p53. Taken together, our findings suggest that, the expression of HIF-1a and VEGF is increased in proliferating phase HA, and OMT suppresses cell proliferation and induces cell apoptosis and cycle arrest in proliferative phase HA through inhibition of the HIF-1a signaling pathway, suggesting OMT may provide a novel therapeutic strategy for the treatment of HA.

Knockdown of IGF2R suppresses proliferation and induces apoptosis in hemangioma cells in vitro and in vivo.

Insulin-like growth factor-II (IGF-II)/IGF2R signaling plays a pivotal role in cell growth, migration and differentiation in many malignancies. An individual with high IGF-II expression levels has a high risk of developing cancer, but IGF2R is often considered to be a tumor suppressor. To date, little has been reported about the role of IGF-II/IGF2R signaling in hemangiomas (HAs). Thus, uncovering the mechanisms of IGF-II/IGF2R signaling is very important to understanding the development of HAs. In the present study, the expression of IGF-II and IGF2R was investigated in 27 cases of HAs of different phases by immunohistochemistry. Through lentivirus-mediated IGF2R siRNA (Lv-siIGF2R) in HA-derived endothelial cells (HDECs), we observed the effects of IGF2R knockdown on the biological behavior of HA cells. We found that the expression of IGF-II and IGF2R was significantly increased in proliferating phase HAs, but decreased in involuting phase HAs. Furthermore, knockdown of IGF2R in vitro significantly diminished the proliferative activity and induced apoptosis and cycle arrest with decreased expression of PCNA, Ki-67, Bcl-2, Cyclin D1 and E and increased the expression of Bax in the proliferative phase HAs (HDEC and CRL-2586 EOMA cells). In addition, the tumor volumes in a subcutaneous HDEC nude mouse model treated with Lv-siIGF2R were significantly smaller than those of the control group. Taken together, our findings indicate that the expression of IGF-II and IGF2R is increased in proliferating phase HAs, and knockdown of IGF2R suppresses proliferation and induces apoptosis in HA cells in vitro and in vivo, suggesting that IGF2R may represent a novel therapeutic target for the treatment of human HAs.

Knockdown of VEGFR2 inhibits proliferation and induces apoptosis in hemangioma-derived endothelial cells.

Angiogenesis is a process of development and growth of new capillary blood vessels from pre-existing vessels. Angiogenic growth factors play important roles in the development and maintenance of some malignancies, of which vascular endothelial growth factor (VEGF)/VEGFR2 interactions are involved in proliferation, migration, and survival of many cancer cells. The aim of this study was to investigate the function of VEGFR2 in human hemangiomas (HAs). Using immunohistochemistry assay, we examined the expression levels of VEGF, VEGFR2, Ki-67, glucose transporter-1 (Glut-1), phosphorylated protein kinase B (p-AKT) and p-ERK in different phases of human HAs. Positive expression of VEGF, VEGFR2, Ki-67, Glut-1, p-AKT and p-ERK was significantly increased in proliferating phase HAs, while decreased in involuting phase HAs (P=0.001; P=0.003). In contrast, cell apoptotic indexes were decreased in proliferating phase HAs, but increased in involuting phase HAs (P<0.01). Furthermore, we used small hairpin RNA (shRNA)-mediated VEGFR2 knockdown in primary HA-derived endothelial cells (HemECs) to understand  the  role  of  VEGF/VEGFR2 signaling. Knockdown of VEGFR2 by Lv-shVEGFR2 inhibited cell viability and induced apoptosis in primary HemECs companied with decreased expression of p-AKT, p-ERK, p-p38MAPK and Ki-67 and increased expression of caspase-3 (CAS-3). Overexpression of VEGFR2 promoted cell viability and blocked apoptosis in Lv-VEGFR2-transfected HemECs. Taken together, our findings demonstrate that, increased expression of VEGFR2 is involved in the development of primary HemECs possibly through regulation of the AKT and ERK pathways, suggesting that VEGFR2 may be a potential therapeutic target for HAs. 

Knockdown of Livin inhibits growth and invasion of gastric cancer cells through blockade of the MAPK pathway in vitro and in vivo.

Livin, a novel member of the human inhibitors of apoptosis protein family, has been shown to be critical for tumor progression and poor prognosis for several types of malignancies. However, limited reports exist regarding the biological functions of Livin in human gastric cancer (GC). The present study investigated the clinical significance of Livin and caspase-3 (CAS-3) in human GC using immunohistochemistry assay, and explore the potential using RNA interference to knockdown Livin expression, including the subsequent effects on tumor growth and invasion in GC cells in vitro and in vivo. Our results showed that the rate of positive expression of Livin was significantly higher in GC tissues compared to that in adjacent non-cancer tissues (ANCT) (64.1 vs. 30.8%, P<0.001), while CAS-3 was lower in GC tissues than in ANCT (33.3 vs. 66.7%, P=0.001). Livin expression was positively correlated with tumor differentiation and lymph node metastases (P=0.009; P=0.007), while CAS-3 was negatively correlated with them (P=0.036; P=0.002) in patients with GC. Furthermore, knockdown of Livin inhibited cell proliferative activities and invasive potential, and induced cell in situ apoptosis in GC cells, accompanied with decreased expression of p38 MAPK, VEGF and MMP-2 and increased expression of CAS-3. In addition, the tumor volumes in the SGC7901 subcutaneous nude mouse model treated with Lv-shLivin was significantly smaller compared to those of the PBS group (P<0.01). Taken together, our findings indicate that the expression of Livin is increased in human GC and correlates with tumor differentiation and lymph node metastases, while knockdown of Livin inhibits cell growth and invasion through blockade of the MAPK pathway in GC cells, suggesting that Livin may be a potential therapeutic target for the treatment of GC.

Combined blockade of AKT/mTOR pathway inhibits growth of human hemangioma via downregulation of proliferating cell nuclear antigen.

Protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway plays a crucial role in the tumorigenesis and progression of multiple tumors, and has been shown to be important therapeutic targets for cancer. The present study aimed to explore the role and molecular mechanisms of AKT/mTOR pathway in human hemangioma (HA). Twenty-five cases of human HA tissues were collected. The expression of AKT, mTOR and proliferating cell nuclear antigen (PCNA) proteins was evaluated using semi-quantitative immunohistochemistry in biopsy samples in different phases of HA. AKT/mTOR pathway was blocked by recombinant small hairpin RNA adenovirus vector rAd5-AKT+mTOR (rAd5-Am), used for infecting proliferating phase HA-derived endothelial cells (HDEC). The expression of AKT, mTOR and PCNA was detected by Real-time PCR and Western blot assays. Cell proliferative activities were determined by MTT assay, and cell cycle distribution and apoptosis were analyzed by flow cytometry. As a consequence, the expression of AKT, mTOR and PCNA was significantly increased in proliferative phase HA, while that was decreased in involutive phase. Combined blockade of AKT/mTOR pathway by rAd5-Am diminished cell proliferative activities, and induced cell apoptosis and cycle arrest with the decreased expression of AKT, mTOR and PCNA in proliferative phase HDEC. In conclusion, the activity of AKT/mTOR pathway was increased in proliferative phase HA, while it was decreased in involutive phase. Combined blockade of AKT/mTOR pathway might suppress cell proliferation via down-regulation of PCNA expression, and induce apoptosis and cycle arrest in proliferative phase HDEC, suggesting that AKT/mTOR pathway might represent the important therapeutic targets for human HA.