Design, synthesis, and biological evaluation of novel benzimidazole derivatives as anti-cervical cancer agents through PI3K/Akt/mTOR pathway and tubulin inhibition.

Phosphatidylinositol 3-kinase (PI3K) is one of the most attractive therapeutic targets for cervical cancer treatment. In this study, we designed and synthesized a series of benzimidazole derivatives and evaluated their anti-cervical cancer activity. Compound 4r exhibited strong antiproliferative activity in different cervical cancer cell lines HeLa, SiHa and Ca Ski, and relative lower cytotoxicity to normal hepatic and renal cell lines LO2 and HEK-293t (IC50 values were at 21.08 µM and 23.96 µM respectively). Its IC50 value was at 3.38 µM to the SiHa cells. Further mechanistic studies revealed that 4r induced apoptosis, arrested cell cycle in G2/M phase, suppressed PI3K/Akt/mTOR pathway and inhibit the polymerization of tubulin. Molecular docking study suggested that 4r formed key H-bonds action with PI3Kα (PDB ID:8EXU) and tubulin (PDB ID:1SA0). Zebrafish acute toxicity experiments showed that high concentrations of 4r did not cause death or malformation of zebrafish embryos. All these results demonstrated that 4r would be a promising lead candidate for further development of novel PI3K and tubulin dual inhibitors in cervical cancer treatment.

Myocarditis complicated by massive right ventricular thrombus and extensive pulmonary embolism: A case report.

An intracardiac thrombus may develop as a consequence of myocarditis, and in rare cases, a dominantly right ventricular thrombus develops, which may impair cardiac function and even cause life-threatening cardiovascular events. We report a 24-year-old man presented with recurrent episodes of palpitation and precordial discomfort after catching a cold 2 months ago. Transthoracic echocardiography (TTE) and computed tomography pulmonary angiogram (CTPA) revealed a mass attached to the apex of the right ventricle and extensive bilateral pulmonary artery emboli. There was no indication where the thrombi originated from in this young patient without any underlying disease except myocarditis. Pulmonary endarterectomy and embolectomy of pulmonary arteries and right ventricle were performed. Postoperative pathological results confirmed the presence of fibrinous necrosis and hemosiderin deposition. The formation of an intraventricular thrombus is closely related to myocarditis, which can affect individuals of all ages, but especially young people. Thus, patients with myocarditis should be closely monitored and followed up because of the increased risk of extensive thrombosis.

Aspiration as the first-choice procedure for airway management in an infant with large epiglottic cysts: A case report.

BACKGROUND: Epiglottic cysts is a rare but potentially lethal supraglottic airway pathology in infants due to the high risk of cannot intubation or cannot ventilation. Awake fiberoptic intubation appeared to be the safest technique, but it is very challenging in infants with large epiglottic cysts. Even it has the risk of airway loss. We report that cyst aspiration is an effective treatment as the first-choice procedure for airway management in an infant with large epiglottic cysts. CASE SUMMARY: A 46-day-old male infant weighing 2.3 kg presented to the emergency room with difficulty feeding, worsening stridor, and progressive respiratory distress. Epiglottic cysts was diagnosed, but fibro bronchoscopy examination failed, as the fiberoptic bronchoscope was unable to cross the epiglottic cysts to the trachea. The infant was transferred to the operating room for emergency cystectomy under general anesthesia. Spontaneous respiration was maintained during anesthesia induction, and cyst aspiration was performed as the first procedure for airway management under video laryngoscopy considering that the preoperative fibro bronchoscopy examination failed. Then, the endotracheal tube was intubated successfully. Cystectomy was performed uneventfully, and the infant was safely transferred to the intensive care unit after surgery. The infant was extubated smoothly on the third postoperative day and discharged on the eighth day after surgery. On follow-up 1 year after the surgery, a normal airway was found by fibro bronchoscopy examination. CONCLUSION: Epiglottic cyst aspiration can be considered the first procedure for airway management in infants with large epiglottic cysts.

Advances in the clinical application of oxycodone in the perioperative period.

To review the research progress of pure opioid receptor agonist oxycodone. The research progress of oxycodone in terms of pharmacokinetics, pharmacodynamics, adverse reactions, clinical application, combined medication and new progress in clinical application was summarized by referring to the literature. Oxycodone is a semi-synthetic thebaine derivative of opioid alkaloids, and is a pure opioid µ and κ receptor agonist. The main action sites are the central nervous system and visceral smooth muscle. Due to its advantages of low adverse reactions, good analgesic effects, and a wide range of safe doses, the drug has been widely used in the control of acute and chronic postoperative pain, as well as malignant and non-malignant pain. Since the end of the 20th century, researchers have begun to formulate antipyretic analgesics, opioid receptor agonists, opioid receptor antagonists, dopamine receptor antagonists and other drugs with oxycodone in different proportions to enhance the analgesic effect. At the same time, it can reduce the dosage of oxycodone and reduce its adverse reactions, so as to achieve the purpose of limiting opioid abuse. With the continuous research on the efficacy and safety of oxycodone in the perioperative period at home and abroad, oxycodone has become the only dual-opioid potent analgesic that can be used in clinical work.

Long noncoding RNA Gas5 induces cell apoptosis and inhibits tumor growth via activating the CHOP-dependent endoplasmic reticulum stress pathway in human hepatoblastoma HepG2 cells.

In recent years, long noncoding RNAs (lncRNAs) have been demonstrated to be important tumor-associated regulatory factors. LncRNA growth arrest-specific transcript 5 (Gas5) acts as an anti-oncogene in most cancers. Whether Gas5 acts as an oncogene or anti-oncogene in hepatocellular carcinoma (HCC) remains unclear. In the present study, the expression and role of Gas5 in HCC were investigated in vitro and in vivo. Lower expression levels of Gas5 were determined in HCC tissues and cells by quantitative reverse transcription-polymerase chain reaction. Overexpressed Gas 5 lentiviral vectors were constructed to analyze their influence on cell viability, migration, invasion, and apoptosis. Fluorescence in situ hybridization was used to identify the subcellular localization of Gas5. Protein complexes that bound to Gas5 were isolated from HepG2 cells through pull-down experiments and analyzed by mass spectrometry. A series of novel Gas5-interacting proteins were identified and bioinformatics analysis was carried out. These included ribosomal proteins, proteins involved in protein folding, sorting, and transportation in the ER, some nucleases and protein enzymes involved in gene transcription, translation, and other proteins with various functions.78 kDa glucose-regulated protein (GRP78) was identified as a direct target of Gas5 by Rip-qPCR and Western blot analysis assay. Gas5 inhibited HepG2 cell growth and induced cell apoptosis via upregulating CHOP to activate the ER stress signaling pathway. Further studies indicated that the knockdown of CHOP by shRNA partially reversed Gas5-mediated apoptosis in HepG2 cells. Magnetic resonance imaging showed that the ectopic expression of Gas5 inhibited the growth of HCC in nude mice. These findings suggest that Gas5 functions as a tumor suppressor and induces apoptosis through activation of ER stress by targeting the CHOP signal pathway in HCC.

The long-term survival outcomes of gastric cancer patients with total intravenous anesthesia or inhalation anesthesia: a single-center retrospective cohort study.

BACKGROUND: The relationship between the type of anesthesia and the survival outcomes of gastric cancer patients is uncertain. This study compared the overall outcome of gastric cancer patients after surgery with total intravenous anesthesia (TIVA) or inhalation anesthesia (IHA). METHODS: Clinicopathological variables of gastric cancer patients were retrieved from the database of the Surgical Gastric Cancer Patient Registry in West China Hospital, Sichuan University. Patients were grouped according to whether they received TIVA or IHA during the operation. Propensity score (PS) matching was used to balance the baseline variables, and survival outcomes were compared between these two groups. In addition, studies comparing survival outcomes between TIVA and IHA used for gastric cancer surgery and published before April 20th, 2020, were identified, and their data were pooled. RESULTS: A total of 2827 patients who underwent surgical treatment from Jan 2009 to Dec 2016 were included. There were 323 patients in the TIVA group and 645 patients in the IHA group, with 1:2 PS matching. There was no significant difference in overall survival outcomes between the TIVA and IHA groups before matching the cohort (p = 0.566) or after matching the cohort (p = 0.679) by log-rank tests. In the Cox hazard regression model, there was no significant difference between the TIVA and IHA groups before (HR: 1.054, 95% CI: 0.881-1.262, p = 0.566) or after (HR: 0.957, 95% CI: 0.779-1.177, p = 0.679) PS matching. The meta-analysis of survival outcomes between the TIVA and IHA groups found critical statistical value in the before PS matching cohort (HR 0.74, 95% CI: 0.57-0.96 p < 0.01) and after PS matching cohort (HR: 0.65, 95% CI: 0.46-0.94, p < 0.01). CONCLUSIONS: Combined with the results of previous studies, total intravenous anesthesia has been shown to be superior to inhalation anesthesia in terms of overall survival for gastric cancer patients undergoing surgical treatment. The selection of intravenous or inhalation anesthesia for gastric cancer surgery should take into account the long-term prognosis of the patient.

Monocytic MDSC mobilization promotes tumor recurrence after liver transplantation via CXCL10/TLR4/MMP14 signaling.

Tumor recurrence is the major obstacle for pushing the envelope of liver transplantation for hepatocellular carcinoma (HCC) patients. The inflammatory cascades activated by acute liver graft injury promote tumor recurrence. We aimed to explore the role and mechanism of myeloid-derived suppressor cell (MDSC) mobilization induced by liver graft injury on tumor recurrence. By analyzing 331 HCC patients who received liver transplantation, the patients with graft weight ratio (GWR, the weight of liver graft divided by the estimated standard liver weight of recipient) <60% had higher tumor recurrence than GWR ≥60% ones. MDSCs and CXCL10/TLR4 levels were significantly increased in patients with GWR <60% or tumor recurrence. These findings were further validated in our rat orthotopic liver transplantation model. In CXCL10-/- and TLR4-/- mice of hepatic ischemia/reperfusion injury plus major hepatectomy (IRH) model, monocytic MDSCs, instead of granulocytic MDSCs, were significantly decreased. Importantly, CXCL10 deficiency reduced the accumulation of TLR4+ monocytic MDSCs, and CXCL10 increased MDSC mobilization in the presence of TLR4. Moreover, MMP14 was identified as the key molecule bridging CXCL10/TLR4 signaling and MDSC mobilization. Knockout or inhibition of CXCL10/TLR4 signaling significantly reduced the tumor growth with decreased monocytic MDSCs and MMP14 in the mouse tumor recurrent model. Our data indicated that monocytic MDSCs were mobilized and recruited to liver graft during acute phase injury, and to promote HCC recurrence after transplantation. Targeting MDSC mobilization via CXCL10/TLR4/MMP14 signaling may represent the therapeutic potential in decreasing post-transplant liver tumor recurrence.

Anesthetic management of a child with double outlet right ventricle and severe polycythemia: A case report.

BACKGROUND: Double outlet right ventricle (DORV) is a rare and complex congenital heart defect, and the surgical repairs vary with type and pathophysiology consequences. Due to prolonged progressive hypoxemia, severe polycythemia is common in patients with DORV, which ultimately leads to coagulation dysfunction and increases the risk of thrombosis and infarction. Consequently, the anesthetic management is challenging and how to manage severe polycythemia and avoid hypoxia-related complications in such patients is of great significance. CASE SUMMARY: Herein, we report the anesthetic management of a 10-year-old female patient with a DORV. She lived in the low-oxygen Qinghai-Tibet Plateau, and presented with severe polycythemia (hemoglobin, 24.8 g/dL; hematocrit, 75%). She underwent a modified Fontan surgery, which was satisfactory and without any perioperative complications. Our anesthetic management highlights the importance of perioperative hemodilution in decreasing the risk of thromboembolism and the importance of correcting coagulopathy in preventing hemorrhage. CONCLUSION: Anesthetic management is challenging in rare cyanotic congenital heart disease patients with severe polycythemia. It is important to adopt perioperative hemodilution and correction of coagulopathy in preventing thrombosis and hemorrhage.

Successful experience in dealing with tooth aspiration after extubation: a case report.

There is a high incidence of tooth injury or loss due to endotracheal intubation or extubation. Tooth injury may be costly or even life threatening. In particular, tooth aspiration may cause airway obstruction, aspiration pneumonitis, or lung collapse, but tooth aspiration after tracheal extubation is rarely reported and easily overlooked. A missing tooth after extubation can be more dangerous. However, there are no practical guidelines and standard intervention strategies to deal with a loose or missing tooth. This article presents the case of a 67-year-old man who underwent laparoscopic colectomy for a colonic tumor under general anesthesia, and whose left maxillary incisor was loose. After surgery, the loose tooth was missing and we had to go through a difficult process to find it. Finally, a chest X-ray revealed a foreign body located in the trachea, and it was successfully removed by fiber-bronchoscopy. The patient woke up with no discomfort and was discharged without complications on the third day after surgery. Based on our experience in this case, we put forward a complete and effective flowchart named "VICTOR" as an option for the prevention of tooth loss and aspiration during surgical procedures and for locating a missing tooth in a timely, appropriate and safe way during the perioperative period.

ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma: A Changing Paradigm in Modulation of Future Liver Remnant Before Major Hepatectomy.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term outcome of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatitis-related hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: ALPPS has been advocated for future liver remnant (FLR) augmentation in liver metastasis or noncirrhotic liver tumors in recent years. Data on the effect of ALPPS in chronic hepatitis or cirrhosis-related HCC remained scarce. METHODS: Data for clinicopathological details, portal hemodynamics, and oncological outcome were reviewed for ALPPS and compared with portal vein embolization (PVE). Tumor immunohistochemistry for PD-1, VEGF, and AFP was evaluated in ALPPS and compared with PVE and upfront hepatectomy (UH). RESULTS: From 2002 to 2018, 148 patients with HCC (hepatitis B: n = 136, 92.0%) underwent FLR modulation (ALPPS, n = 46; PVE: n = 102). One patient with ALPPS and 33 patients with PVE failed to proceed to resection (resection rate: 97.8% vs 67.7%, P < 0.001). Among those who had resections, 65 patients (56.5%) had cirrhosis. ALPPS induced absolute FLR volume increment by 48.8%, or FLR estimated total liver volume ratio by 12.8% over 6 days. No difference in morbidity (20.7% vs 30.4%, P = 0.159) and mortality (6.5% vs 5.8%, P = 1.000) with PVE was observed. Chronic hepatitis and intraoperative indocyanine green clearance rate ≤39.5% favored adequate FLR hypertrophy in ALPPS. Five-year overall survival for ALPPS and PVE was 46.8% and 64.1% (P = 0.234). Tumor immunohistochemical staining showed no difference in expression of PD-1, V-EGF, and AFP between ALPPS, PVE, and UH. CONCLUSIONS: ALPPS conferred a higher resection rate in hepatitis-related HCC with comparable short- and long-term oncological outcome with PVE.

Long non­coding RNA MEG3 suppresses epithelial­to­mesenchymal transition by inhibiting the PSAT1­dependent GSK­3ß/Snail signaling pathway in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer in China, and the prognosis of patients remains poor mainly due to the occurrence of lymph node and distant metastasis. The long non­coding RNA (lncRNA) maternally expressed gene 3 (MEG3) has been shown to have tumor­suppressive properties and to play an important role in epithelial­to­mesenchymal transition (EMT) in some solid tumors. However, whether MEG3 is involved in EMT in ESCC remains unclear. In the present study, the MEG3 expression level and its association with tumorigenesis were determined in 43 tumor tissues of patients with ESCC and in ESCC cells using reverse transcription­quantitative PCR analysis. Gene microarray analysis was performed to detect differentially expressed genes (DEGs). Based on the functional annotation results, the effects of ectopic expression of MEG3 on cell growth, migration, invasion and EMT were assessed. MEG3 expression level was found to be markedly lower in tumor tissues and cells. Statistical analysis revealed that MEG3 expression was significantly negatively associated with lymph node metastasis and TNM stage in ESCC. Fluorescence in situ hybridization assay demonstrated that MEG3 was expressed mainly in the nucleus. Ectopic expression of MEG3 inhibited cell proliferation, migration, invasion and cell cycle progression in EC109 cells. Gene microarray results demonstrated that 177 genes were differentially expressed ≥2.0 fold in MEG3­overexpressing cells, including 23 upregulated and 154 downregulated genes. Functional annotation revealed that the DEGs were mainly involved in amino acid biosynthetic process, mitogen­activated protein kinase signaling, and serine and glycine metabolism. Further experiments indicated that the ectopic expression of MEG3 significantly suppressed cell proliferation, migration, invasion and EMT by downregulating phosphoserine aminotransferase 1 (PSAT1). In pathological tissues, PSAT1 and MEG3 were significantly negatively correlated, and high expression of PSAT1 predicted poor survival. Taken together, these results suggest that MEG3 may be a useful prognostic biomarker and may suppress EMT by inhibiting the PSAT1­dependent glycogen synthase kinase­3ß/Snail signaling pathway in ESCC.

Survival analysis of intraoperative blood salvage for patients with malignancy disease: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Intraoperative blood salvage as a blood-saving strategy has been widely used in surgery. Considering its theoretic risk of malignant tumor cells being reinfused and the corresponding blood metastases, the safety of intraoperative blood salvage in cancer surgery remains controversial. METHODS: Following the Preferred Reporting Items for Systemic Review and Meta-Analysis (PRISMA), we searched the Cochrane Library, MEDLINE and EMBASE to November 2017. We included only studies comparing intraoperative blood salvage with allogeneic blood transfusion. RESULTS: This meta-analysis included 9 studies with 4354 patients with 1346 patients in the intraoperative blood salvage group and 3008 patients in the allogeneic blood transfusion group. There were no significant differences in the 5-year overall survival outcome (odds ratio [OR] 1.12; 95% confidence interval [CI], 0.80-1.58), 5-year disease-free survival outcome (OR 1.08; 95% CI 0.86-1.35), or 5-year recurrence rate (OR 0.86; 95% CI 0.71-1.05) between the 2 study groups. Subgroup analysis also showed no significant differences in the 5-year overall survival outcome (OR 0.97; 95% CI 0.57-1.67) of hepatocellular carcinoma patients in liver transplantation. CONCLUSIONS: For patients with malignant disease, intraoperative blood salvage did not increase the tumor recurrence rate and had comparable survival outcomes with allogeneic blood transfusion.

Risk factors of the postoperative 30-day readmission of gastric cancer surgery after discharge: A PRISMA-compliant systematic review and meta-analysis.

BACKGROUND: Readmission is a common postoperative adverse event. This study aimed to analyze potential risk factors for the incidence of postoperative 30-day readmission after discharge for gastric cancer patients with surgical treatment. METHODS: Those studies that reported the risk factors of gastric cancer patients who have a postoperative 30-day readmission were identified systematically from the PubMed, Cochrane, and Embase databases through July 2018. A systematic review and meta-analysis was performed to estimate the risk factors of postoperative 30-day readmission after gastric cancer surgery. RESULTS: Ultimately, 6 studies with 12,586 gastric cancer patients were included in the present study. There were 1473 (11.7%) patients who had postoperative 30-day readmission and 12,586 (88.3%) patients without 30-day postoperative readmission. A greater proportion of the readmission group had cardiovascular comorbidity (P < .001), pulmonary comorbidity (P < .001), and diabetes mellitus (P = .020) than the nonreadmission group. Furthermore, more patients in the readmission group had total gastrectomy (P < .001), combined organ resection (P < .001) and postoperative complications (P < .001) than did patients in the nonreadmission group. Nonhome discharge (odds ratio [OR] 1.580, P = .002), diabetes mellitus (OR 1.181, P = .044), postoperative complications (OR 2.656, P = .006), total gastrectomy (OR 2.242, P < .001), and combined organ resection (OR 1.534, P < .001) were independent risk factors for postoperative readmission. CONCLUSION: Postoperative readmission is influenced by the synthetic action of preparative, intraoperative, and postoperative factors, such as diabetes mellitus, total gastrectomy, combined organ resection, nonhome discharge, and postoperative complications. Extra attention should be paid to those patients with high risk factors during the postoperative follow-up and recovery periods.

Suppression of long noncoding RNA NCK1-AS1 increases chemosensitivity to cisplatin in cervical cancer.

Cervical cancer remains a serious health problem till now, with nearly 500,000 women cases diagnosed each year around the world. Long noncoding RNA (lncRNA) is a novel class of RNA transcripts (>200 nucleotides in length) participating in gene transcription, cell proliferation, differentiation, and drug resistance. This study aimed to explore the regulatory relationship among lncRNA NCK1-AS1, miR-134-5p, and MutS protein homolog 2 (MSH2), so that the resistance against cisplatin in cervical cancer treatment could be better understood. Comprehensive lncRNA profiling analysis was performed to screen lncRNAs differentially expressed in cervical cancer. The expression patterns of miR-134-5p, NCK1-AS1, and MSH2 were evaluated in cancerous tissues and adjacent normal tissues obtained from 75 cervical cancer patients. Subsequently, anti-NCK1-AS1 small interfering RNA, miR-134-5p mimics, and miR-134-5p inhibitors were transfected into cervical cancer cells, and the effects of these transcripts on cisplatin resistance and cell apoptosis were investigated. The regulatory relationship among NCK1-AS1, miR-134-5p, and MSH2 was identified using a dual-luciferase reporter gene assay, and the results were further validated by RNA pull-down and RNA immunoprecipitation assays. Based on the microarray data of GSE63514 and GSE27678, NCK1-AS1 was upregulated in cervical cancer. Increased expression of NCK1-AS1, MSH2, and decreased expression of miR-134-5p were observed in cervical cancer tissues. In addition, NCK1-AS1 competitively bound to miR-134-5p to regulate MSH2. Therefore, si-NCK1-AS1 and miR-134-5p mimic both reduced MSH2 activity and increased cisplatin-induced apoptosis in cervical cancer cells. Taken together, NCK1-AS1 may become a novel target in improving the chemotherapeutic response and survival of cervical cancer patients.

Down-regulation of long non-coding RNA ANRIL inhibits the proliferation, migration and invasion of cervical cancer cells.

OBJECTIVES: Cervical cancer (CC) is a common malignant tumor in the female reproductive system that is characterized by a high metastatic potential. LncRNA ANRIL has been found to be a cancer oncogene in multiple tumors. In our study, we altered the expression of ANRIL in CC cells and evaluated its ability on influencing proliferation, migration and invasion of CC cells and associated mechanism. METHODS: Differentially expressed lncRNAs in CC were identified by microarray and TCGA analyses. CC tissues and adjacent tissues were collected in order to extract CC cells. The expression of ANRIL was determined by RT-qPCR. The CC cells were transfected with siRNA or si-NC against ANRIL to find out whether ANRIL can influence the expression of Cyclin D1, CDK4, CDK6, E-cadherin, vimentin and N-cadherin, as well as affect cell proliferation, cell apoptosis, cell migration and cell invasion of CC cells. RESULTS: Based on TCGA and microarray analyses, ANRIL was predicted to be highly expressed in CC and CC with migration. Then further verification was obtained by means of RT-qPCR that ANRIL was highly expressed in CC tissues. In addition, high expression of ANRIL was related to increased E-cadherin expression, high migration of CC as well as decreased cell apoptosis rate. On the other hand, inhibition of ANRIL expression led to decreased expressions of Cyclin D1, CDK4, CDK6, N-cadherin and Vimentin, along with attenuated cell proliferation, migration and invasion of CC cells. CONCLUSION: The key findings of our study demonstrated that the inhibition of lncRNA ANRIL reduces the proliferation, migration and invasion capabilities of CC cells. Down-regulation of ANRIL may serve as a potential therapeutic target in the treatment of CC.

An special epithelial staining agents: folic acid receptor-mediated diagnosis (FRD) effectively and conveniently screen patients with cervical cancer.

High-quality screening with cytology has markedly reduced mortality from cervical cancer. However, it needs experienced pathologists to review and make the final decisions. We have developed folic acid receptor-mediated diagnosis (FRD) kits to effectively and conveniently screen patients with cervical cancer. We conduct present study aim to assess clinical significances of FRD in screening cervical cancer. A total of 169 patients were enrolled at Chinese People's liberation Army (PLA) general hospital. We compared diagnostic significances of FRD with thinprep cytology test (TCT). Meanwhile, colposcopy was also performed to confirm any lesion suspicious for cervical cancer. The sensitivity and specificity of FRD were 71.93% and 66.07% in diagnosis cervical cancer, respectively. Meanwhile, the positive predictive values (PPV), negative predictive values (NPV), Youden index were 51.90%, 82.22%, 0.38, respectively. On the other hand, the sensitivity and specificity of TCT in diagnosis cervical cancer were 73.68% and 61.61% respectively. PPV, NPV and Youden index for TCT were 49.41%, 82.14% and 0.35 respectively. Overall, FRD have high values of sensitivity, specificity and Youden index. However, this difference failed to statistical significance. FRD have comparable diagnostic significance with TCT. Therefore, FRD might serve as one effective method to screen cervical cancer. Especially for those patients living in remote regions of China, where cytology was unavailable.

Expression of aquaporin 1 in bladder uroepithelial cell carcinoma and its relevance to recurrence.

OBJECTIVES: To explore the expression of aquaporin 1 (AQP1) in bladder uroepithelium cell carcinoma (BUCC) and its relevance to recurrence. MATERIALS AND METHODS: Tissue samples from 45 BUCC patients who underwent total cystectomy or transurethral resection of bladder tumor (TURBT) and from 40 patients with non-bladder cancers who underwent special detection or treatments were collected. The level of expression of AQP1 in BUCC tissues and normal bladder tissues was assessed by immunohistochemistry so as to analyze the relevance to pathological patterns and time of recurrence in BUCC patients. RESULTS: The expression levels of AQP1 normal bladder tissues and BUCC tissues were 2.175±0.693 and 3.689±0.701, respectively, and the difference was significant (t=9.99, P<0.0001). Marked increase was noted with BUCC histological grade and pathological stage (P<0.01). Moreover, the expression of AQP1 was evidently higher in cancerous tissues with lymph node metastasis than in those without (P<0.01). With short-term recurrence, the positive cell expression rate of AQP1 was higher in primary tissues, which increased obviously after recurrence. Additionally, the recurrent time of BUCC was negatively associated with the positive cell expression rate of AQP1 and the difference between the expression of AQP1 before and after recurrence (r=-0.843, F=39.302, P=0.000; r=-0.829, F=35.191, P=0.000). CONCLUSIONS: AQP1, which reflects the grade, stage, lymph node metastasis and recurrence of BUCC, has potential guiding significance in the diagnosis and treatment of bladder cancarcinoma.

Ingol-type diterpenes from Euphorbia antiquorum with mouse 11ß-hydroxysteroid dehydrogenase type 1 inhibition activity.

Eighteen new ingol-type diterpenes, euphorantins A-R (1-18), along with four known analogues (19-22), were isolated from the aerial parts of Euphorbia antiquorum. Compounds 1-3 are the first examples of C-17-oxygenated ingol-type diterpenes, and compounds 16-18 represent a rare class of 2,3-di-epimers of ingols. Diterpenes 1, 14, and 22 exhibited inhibitory activities against mouse 11ß-HSD1 with IC50 values of 12.0, 6.4, and 0.41 µM, respectively.

Beneficial effects of the Chinese herbal medicine Sanjie Zhentong Capsule on experimental endometriosis in rats.

AIM: To analyze the composition of the Chinese herbal medicine Sanjie Zhentong Capsule (SJZTC) and test the therapeutic efficacy of each component in a rat model of endometriosis. METHODS: A rapid resolution liquid chromatography (RRLC) method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (Q-TOF MS) has been developed for the analysis of SJZTC. Two main ingredients, Drac(h)onis sanguis and saponin, were tested in the endometriosis model. Sixty Lewis female rats were in the estrous cycle stage when endometriosis was experimentally initiated by peritoneal implantation of endometrial tissue. Four weeks later, a second laparotomy was performed and implant volumes were measured. After that, the implanted rats were randomized into five study groups: control group (treatment with saline), anastrozole group (treatment with anastrole, 18 µg per day), loureirin A group (treated with loureirin A, 97.2 mg), ginsenoside Re group (treated with ginsenoside Re, 64.8 mg), and SJZTC groups (treated with SJZTC, 86.4 mg) administered once a day for 4 weeks via gastric gavage. After four weeks of treatment, a third laparotomy was performed, implant volumes were re-measured, and the levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were tested. RESULTS: A total of 38 compounds including, both the target and unknown compounds, were rapidly predicted in the capsule extract by the developed method. Compared with the control group, the anastrozole group, loureirin A group, ginsenoside Re group, and SJZTC treated group showed smaller implant volumes, as well as lower levels of VEGF and TNF-α in the peritoneal focus (P < 0.01 for all comparisons). Furthermore, parameters in the groups treated with SJZTC, loureirin A and ginsenoside Re were significantly better than the control group and the anastrozole group. These results indicate that SJZTC and its two main components are effective in reducing the development of endometriosis.