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Objective: Breast cancer stem cells (BCSC) have been suggested to have clinical implications for cancer therapeutics because of their proposed role in chemo-resistance. The aim of this study was to investigate effects of BCSC on endocrine therapy response by regulating PI3K/Akt/mTOR signaling pathway. Methods: We evaluated the susceptibility of BCSC to NVP-BKM120 (BKM120), a new generation of PI3K-specific inhibitor, when used individually or in combination with letrozole in vivo. For this, a stem-like cell population (SC) was enriched from breast cancer cell line MCF-7 after mammosphere cultures. We have constructed high aromatase expression BCSC (BCSC-CYP19) and non-stem cells (MCF-7-CYP19) subcloning. We demonstrate BKM120 inhibits growth, generation of drug-resistant derivatives and SC formation in BCSC-CYP19 and MCF-7-CYP19. Result: BKM120 could inhibit BCSC-CYP19 growth by dose-dependence, reduce migration and colony formation of BCSC-CYP19, and also significantly reduced expression of PI3K, Akt1 and S6. Combined BKM120 and letrozolecaninhibit BCSC-CYP19 growth and proliferation, make BCSC-CYP19 stayed in G0-G1 phase increasing significantly to induce early apoptosis, and down-regulate expression of PI3K, Akt1 and S6. Conclusion: PI3K/Akt/mTOR pathway effects on letrozole resistance by regulating BCBSs characteristics. Combination of PI3K inhibitor BKM120 and letrozole could reduce letrozole resistance.

Objective: To investigate the usefulness of adrenal androgens for assessing the selectivity of adrenal venous sampling (AVS). Methods: Between January 2010 and December 2016, 37 consecutive patients [with an average age of (47±14) years, 16 males and 21 females] with primary aldosteronism (PA) who underwent AVS were enrolled. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal venous (AV) and peripheral venous (PV) samples, respectively. Results: The selectivity index (SI) based on androstenedione and DHEA was higher than that of cortisol (SI-left: 13.9, 13.1 vs 6.05, P= 0.006, 0.035; SI-right: 30.4, 18.5 vs 11.6, P= 0.028, 0.051). However, the SI based on DHEAS was lower than that of cortisol (SI-left: 1.3 vs 6.0, P= 0.002; SI-right: 1.5 vs 11.6, P= 0.038). Plasma androstenedione and DHEA concentrations were positively correlated with cortisol and aldosterone in AV samples (all P< 0.001). Compared to cortisol, the variation ratio of AV androstenedione and DHEA was lower from t(-15) to t(0) (0.23, 0.43 vs 0.52, both P< 0.05). Using the receiver operating characteristic curve, a SI ≥ 3.0 for androstenedione or DHEA provided optimal sensitivity(97.7%, 91.9%) and specificity (93.8%, 93.8%) in AVS. Conclusion: Given the greater AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors co-secreting cortisol and aldosterone.

Objective: To investigate the therapeutic efficacy and safety of CT-guided radiofrequency ablation(RFA)combined with biopsy synchronously to multiple small nodules of metastatic tumors in lung. Method: From January 2016 to December 2016, a total of 86 patients in the General Hospital of People's Liberation Army with 144 lesions were divide into two groups(all the lesions were less than 1 cm). Group A with 51 cases located in the lung periphery underwent biopsy prior to RFA.Group B with 35 cases located in the middle and inner side of lung adjacent to the vasculatures contrarily underwent RFA first.The changes of these lesions during the 1 to 12-month were followed up. Results: All the procedures were completed successfully.The intra operative CT scanning showed the ablation zones were completely covered by the indicative "halo sign" respectively.The P value was 0.818, 0.155 and 0.452 respectively, in the number of nodules, pathological results positive rate and complications in the rank and inspection for A, B two groups, which were all higher than 0.05.Though different strategies according to different location of the nodes, the two groups can achieve safe and effective treatments.All patients in two groups had high density ablation zones on their 1-month post operative CT without enhancement.3-and 6-post operative CT illustrated a decrease of lesions, 12-month post operative CT showed the lesions turned to fibrous stripes. Conclusion: The CT-guided RFA combined with biopsy synchronously to multiple small nodules of metastatic tumors in lung is safe and effective, for the lesions located in the middle or inner side of lung, RFA prior to the biopsy can avoid the massive hemoptysis.

Objective: To find a suitable method for the determination of citric acid in the urine of patients with stones, in order to provide a new method and basis for the prevention and treatment of stone. Methods: Liquid chromatography tandem mass spectrometry was used to analyze the citric acid in urine directly. And the accuracy, stability, repeatability and other indicators of the results were detected. Results: The results showed a good linear relationship with the concentration of citric acid in urine. y=50.31x+ 0.002 6 ( R (2)=0.994 21). The results were stable, reproducible [intra-day (Coefficient of Variance) CV ≈1% and inter-day CV<10%], and the accuracy of which was comparable with that of the enzyme method ( n =20, R =0.97). Conclusion: Using the method of this study to detect the content of citric acid in urine has the advantages of simple operation, good repeatability, accurate results, and low price. So it is worth to be popularized and applied in clinical practice.

Objective: To investigate the role of adrenal vein sampling (AVS) in identifying the subtype of primary aldosteronism (PA). Methods: AVS was performed in 50 patients who were confirmed as PA between September 2010 and September 2016 in Nanjing Drum Tower Hospital. Clinical, biochemical and follow-up data were reviewed retrospectively. Bilaterally simultaneous catheterization without cosyntropin stimulation and contemporaneous cortisol measurement during AVS were used. Selectivity index (SI)≥1.5 suggested that the sample was from the adrenal vein.Lateralization index (LI) ≥2 suggested unilateral disease.Clinical data was further compared and the AVS findings were analyzed. Results: AVS was successful performed in 41 cases of 50 patients, and the success rate was 82%. According to the results of AVS and postoperative pathology, 41 cases were divided into aldosterone-producing adenoma (APA)/unilateral adrenal hyperplasia (UAH) group (24 cases) and idiopathic hyperaldosteronism (IHA) group (17 cases). Compared with IHA group, patients with APA/UAH showed longer duration of hypertension[10.0 (5.0, 13.0) y vs 4.0 (2.0, 8.0) y, P =0.046], higher proportion of hypokalemia (95.8% vs 64.7%, P =0.009). Furthermore, patients with APA/UAH demonstrated lower plasma renin activity ( P =0.089), higher plasma aldosterone concentration and aldosterone to renin ratio (ARR) (both P <0.05). The diagnostic concordance between CT and adrenal vein sampling was only 48.8%(20/41). Conclusions: The application of bilaterally simultaneous catheterization and contemporaneous cortisol measurement improves success rate and diagnostic accuracy of AVS. AVS is useful in subtype diagnosis of PA with equivocal imaging findings.

Objective: To find a suitable method for the determination of oxalic acid in the urine of patients with stones, in order to provide a new method and basis for the prevention and treatment of stone. Methods: Liquid chromatography combined with tandem mass spectrometry was used to analyze oxalic acid in urine directly.The accuracy, stability, repeatability and other indicators of the results were tested. Results: The results showed a good linear relationship with the concentration of oxalic acid in urine. y=58.524x-15.246 (R(2)=0.979 02). The results were stable, reproducible (the intra-day and inter-day coefficient of variation was less than 10% and 15%, respectively), and the accuracy was comparable with that of the enzyme method (N=20, R=0.93). Conclusion: Using the method of this study to detect the content of oxalic acid in urine has the advantages of simple operation, good repeatability, accurate results, and low price. It is worth to be popularized and applied in clinical practice.

Objective: To explore the diagnosis and treatment of tuberous sclerosis complex complicated with renal angiomyolipoma., Methods: The clinical data of 22 patients with tuberous sclerosis complex complicated with renal angiomyolipoma were analyzed retrospectively., Results: There were 12 males and 10 females with a mean age of 23 (1-46) years. All of them had bilateral multiple renal angiomyolipomas. The mean tumor size was 8.5 (0.7-18.0) cm in diameter. The presence or absence of clinical symptoms showed a significant correlation with tumor size.Eight patients with angiomyolipoma under 4 cm in diameter were continuously monitored at an outpatient clinic. There were 8 patients with lesions of 4-10 cm.Five of them underwent nephron-sparing surgeries and another 3 monitored at an outpatient clinic. There were 6 patients with tumor over 10 cm. Three of them underwent transcatheter arterial embolization and one case took rapamycin after embolization.One patient with concurrent renal cell carcinoma underwent partial nephrectomy. Chronic renal failure occurred in one case dying of pulmonary lymphangiomyomatosis with serious hemoptysis. During a mean follow-up of 25 months, neither severe renal hemorrhage nor symptomatic aggravation was found.In the case of rapamycin, there was 10% reduction in the size of angiomyolipoma., Conclusions: Most cases of tuberous sclerosis complex are complicated with bilateral multiple renal angiomyolipoma. The small lesions under 4 cm in diameter may be monitored at an outpatient clinic.For those larger (>4 cm) or symptomatic ones, medication, embolization or surgery is necessary.

Objective: To evaluate the safety and efficacy of radiation plus erlotinib in patients with esophageal cancer older than 70 years., Methods: Radiotherapy was prescribed at a daily fraction of 2.0 Gy up to a total dose of 60 Gy over 6 weeks. Concurrent erlotinib was administrated at a dose of 150 mg daily at days 1-42. Acute toxicities were assessed by the criteria of Radiation Therapy Oncology Group (RTOG) and National Cancer Institute (NCI). The results were analyzed by the software SPSS 17.0., Results: A total of 33 patients were enrolled. The median survival time was 16.3 ± 8.6 months (95%CI 0.0 - 33.3) and the 1-and 2-year overall survival rates were 66.3% and 49.7% respectively. The media progression-free survival was 16.7 ± 7.1 months (95%CI 2.9 - 30.5) and the 1- and 2-year local control rates 73.3% and 54.9% respectively. Most toxicities were of grade 1-2 and manageable., Conclusion: The combined regimen of radiation and erlotinib is effective and safe in elder patients aged > 70 years with esophageal cancer. However the results of our study should be confirmed in randomized controlled trials of a larger sample size.

Objective: To explore the effects of CTLA4Ig gene-modified dendritic cells on the mechanism of immune regulation in asthma with Th2 superiority., Methods: Newborn BALB/c mice are randomly divided into 2 groups of AdCTLA4Ig-DC intervention and AdGFP modified dendritic cells (AdGFP-DC) intervention by randomization (n = 10 each). CTLA4Ig gene-modified dendritic cells (AdCTLA4Ig-DC) and AdGFP-DC were infused separately. Newborn BALB/c mice in both groups were fed for 6 - 8 weeks. Additional 6 - 8 weeks BALB/c mice were randomly divided into 2 groups of control and asthma (n = 10 each). The saline-sensitized/challenged mice received an intraperitoneal injection while inhalation was administered in the control group. Ovalbumin (OVA) was used similarly in the remaining three groups. The manifestations of OVA challenged mice in each group, bronchoalveolar lavage fluid (BALF) eosinophils and pathological changes in airway were observed to examine the effects of CTLA4Ig gene-modified dendritic cells on airway inflammation. The levels of IgE, Interleukin (IL)-4, IL-10 and IFN-γ were detected by enzyme-linked immunosorbent assay (ELISA)., Results: Rapid respiration and pulmonary inflammatory infiltration were obvious in the asthma group. CTLA4Ig gene-modified dendritic cells transfused neonatally significantly improved the symptoms of asthma in adulthood and reduced the infiltration of inflammatory cells in bronchial submucosa. The levels of IgE and IL-4 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly lower than those in the asthma group (IgE: (3.9 ± 1.3)× 10(5) pg/ml vs (5.3 ± 1.7)× 10(5) pg/ml and (22.9 ± 11.8)× 10(3) pg/ml vs (122.0 ± 59.6)× 10(3) pg/ml, IL-4: (70.5 ± 7.0) pg/ml vs (88.7 ± 9.2) pg/ml and (46.9 ± 2.9) pg/ml vs (73.3 ± 8.7) pg/ml, all P < 0.05). The levels of IL-10 in serum and BALF in the AdCTLA4Ig-DC intervention group were significantly higher than those in the asthma group ((442 ± 8) pg/ml vs (227 ± 11) pg/ml, (83 ± 42) pg/ml vs (27 ± 11) pg/ml, both P < 0.05). The levels of IFN-γ in serum and BALF in AdCTLA4Ig-DC intervention group showed no significant difference with those in the asthma group (both P > 0.05). The eosinophil level in BALF was significantly lower than that in the asthma group ((18.5 ± 1.9)× 10(4)/ml vs (62.3 ± 6.7)× 10(4)/ml, P < 0.05)., Conclusions: CTLA4Ig gene-modified dendritic cells transfused neonatally may reduce the secretion of Th2 cytokines in OVA-sensitized/challenged adult mice. The expression of CTLA4Ig gene induces immune tolerance in asthma.

Objective: To compare the differential phosphorylation level of proteins between relapsed nasopharyngeal carcinoma (rNPC) and primary nasopharyngeal carcinoma (pNPC)., Methods: Total protein was extracted from 4 pNPC tissue and 4 rNPC tissue samples from January 2003 to September 2005. Then it was analyzed by antibody microarray with 656 antibodies. The differential phosphorylation level of proteins was screened and clustering analysis conducted. The phosphorylation status of the protein sites and its functional pathways were analyzed via an online database of PhosphoSite Plus. The protein expressions were detected by immunohistochemistry., Results: Relapsed and primary nasopharyngeal carcinomas had differential phosphorylation level of proteins. And 6 differentially expressed proteins were identified. The phosphorylation levels of KIT, ATP1A1, Synapsin, SEK1 and histone H2AX were up-regulated in rNPC (P = 0.007 - 0.048) while c-Jun was down-regulated (P = 0.030). The expression of P-H2AX in rNPC was significantly higher than that in pNPC [0.390 (0.175) vs 0.290 (0.155)], but p-c-Jun was significantly lower in rNPC than that in pNPC [0.625 (0.145) vs 0.725 (0.178)] (both P < 0.05). Among them, the changes in the phosphorylation levels of c-Jun, histone H2AX, SEK1 and KIT might play important roles in the relapse of NPC through improving DNA damage repair ability, inhibiting apoptosis and promoting tumorigenesis., Conclusion: The changes of protein phosphorylation may help to explain the recurrent mechanisms of NPC and provide new therapeutic anti-recurrence targets.

Objective: To explore the early changes in serum neutrophil elastase (NE) in rats with burn, blast injury or combined burn-blast injury and its significance., Methods: A total of 176 male Sprague Dawley rats were randomly divided into four groups: control (C), burn (BU), blast injury (BL) and burn-blast combined injury (BB). Rats in C group were not injured. Animals in BU group were subjected to 25% TBSA full-thickness burn on back with 94 degrees C water for 12 seconds; Animals in BL group were inflicted with moderate blast injury with 5 g 8701 compressed dynamite stick as the explosion source 75 cm away while left chest facing the explosive source; Rats in BB group were burned immediately after the blast injury similarly as in BL group. During the first 24 h post-injury, animals in BU and BB groups received intraperitoneal injection of sodium lactate Ringer's solution at a dose of 50 ml x kg(-1) x 12 h(-1). Protein concentration in bronchoalveolar lavage fluid (BALF), water content of lung tissue and NE content in serum were determined at 0 h (C group), 3 h, 6 h, 12 h, 1 d, 2 d, 3 d, 7 d post-injury., Results: Protein concentration in BALF, water content of lung tissue and NE content in serum in SD rats of the injured groups were significantly higher than those in C group (P < 0.01 or P < 0.05), peaked within 2 d post-injury, especially at 2 d post-injury (NE content in serum: BU group, 319. 85 +/- 19.50 ng/ml; BL group, 467.43 +/- 31.64 ng/ml; BB group, 626.00 +/- 26.38 ng/ml vs. C group, 78.53 +/- 25.10 ng/ml). Overall, protein concentration in BALF, water content of lung tissue and NE content in serum in BB group were significantly higher than BU and BL groups (P < 0.01 or P < 0.05). Correlation analysis showed that within 3 d postinjury, a significant positive correlation was found between the protein concentration in BALF, water content of lung tissue and NE content in serum (r = 0.7910, 0.8078, P < 0.05) in BU group. NE content in serum and protein concentration in BALF were significantly positively correlated in BB group (r = 0.8672, P < 0.05)., Conclusion: NE may play an important role in early lung injury of burn or blast injury, especially in combined burn-blast injury.

Objective: To evaluate the gain on the life quality of NPC from efforts to reduce the radiotherapy-induced xerostomia after IMRT., Methods: From August 2002 to December 2008, 235 patients with nasopharyngeal carcinoma were treated with IMRT in the First Affiliated Hospital of Wenzhou Medical College. Ninety-one patients with minimum 2 years of survival and no replaces and metastasis were enlisted. XQ and QOL questionnaires were completed at baseline, then 0, 3, 6, 9, 12, 18 and 24 months after IMRT., Results: The XQ scores were substantially higher at the end of IMRT compared with baseline and descended over time. At 9 months post-RT, the XQ scores improved significantly (P = 0.024) and recovered nearly to baseline at 18 months post-RT. Likewise, the QOL scores were significantly higher at the end of IMRT compared with baseline (P = 0.012) and had a sequential trend towards improvement over the study period. At 18 months post-RT, the QOL scores almost recover to baseline (P = 0.020). Multiple comparisons testing revealed that communication, eating and pain sub-scale scores were significantly higher at the end of IMRT compared with baseline(P < 0.05) with the exception of emotion domain. There was a significant correlation between XQ scores and QOL scores in general in all the study time (r = 0.976, P < 0.001), also a significant position correlation was found between XQ scores and communication, eating sub-scale scores and overall bother scores., Conclusions: IMRT technique can reduce the incidence of postradiation xerostomia significantly and can improve the quality of life in many domains.

Objective: To clone, prepare probe for and explore the expression levels of KIAA1173 gene in skin squamous cell carcinoma (SSCC) and investigate its expression, clinical and pathological significance., Methods: KIAA1173 gene fragment (354 bp) was cloned and its cDNA probe prepared. The expression of KIAA1173 gene in 133 SSCC tissue samples (including 52 specimens of I, 37 specimens of II, 31 specimens of III and 13 specimens of IV) and 47 normal controls were examined by in situ hybridization (ISH). And all specimens were embedded in paraffin., Results: ISH showed brown positive granules in the cytoplasm of parenchymal cells. The positive rate of KIAA1173 mRNA was 38.3% (51/133) in SSCC and 93.6% (44/47) in normal controls. The rate was lower in cancer groups than that in normal tissues (chi(2) = 42.567, P < 0.01). The strongly positive rates were significantly lower in SSCC groups (6.0%, 8/133) than that in normal control (48.9%, 23/47, chi(2) = 44.876, P < 0.01). The negative rates of KIAA1173 mRNA were 53.8% (28/52) in SSCC I, 62.2% (23/37) in SSCC II, 67.7% (21/31) in SSCC III and 76.9% (10/13) in SSCC IV (chi(2) = 4.005, P > 0.05). The negative rates of KIAA1173 mRNA in the dys-good differentiation group (70.5%, 31/44) was higher than that in the good differentiation group (57.3%, 51/89), but there was not significant difference between the two groups (chi(2) = 2.154, P > 0.05)., Conclusion: KIAA1173 gene is highly expressed in normal skin, but it becomes down-regulated in SSCC. It may play an important role in the development of SSCC.

Objective: To investigate the clinicopathological characteristics and differential diagnosis of primary peritoneal adenocarcinoma., Methods: The clinico-pathological data of 8 patients with primary peritoneal adenocarcinoma, all female, aged 55.7 (45 - 69), were analyzed retrospectively. Immunohistochemistry was used to detect the expression of pan-cytokine, cytokine (CK) 7, CK20, CA125, CEA, epithelial membrane antigen (EMA), vimentin, calretinin, and P63 in the specimens of tumor obtained during tumor reduction surgery. Microscopy was conducted for pathological examination., Results: The common clinical symptoms of these 8 patients included abdominal distention and ascites. Pre-operationally, 6 cases were diagnosed as with ovarian cancer, I case as with malignant mesothelioma, and I as with peritoneal carcinoma. The misdiagnosis rate was 87.5%. Post-operational pathological examination showed 7 cases of serous papillary adenocarcinoma and one case of mucinous adenocarcinoma. Immunohistochemistry showed the positive rates of the different biological markers as follows: pan-CK (8/8), CK7 (8/8), CK20 (1/8), CA125 (7/8), CEA (7/8), EMA (8/8), vimentin (1/8), calretinin (1/8), and P53 (8/8)., Conclusion: A rare malignant tumor arising from the secondary Müllerian system, primary peritoneal adenocarcinoma shares similar histopathological characters with ovary carcinoma, so is easy to be misdiagnosed. Immunohistochemical staining is helpful to the differential diagnosis.

Objective: To evaluate the effects of computed tomography (CT) guided percutaneous fine-needle aspiration biopsy (FANB) in examination of pancreas and Vater's ampulla., Methods: One hundred and six patients, 71 males and 35 females, aged 21 approximately 74, with lesions located in the pancreas and Vater's ampulla, 1.5 approximately 5 cm in size (< 3 cm in 32 cases and >or= 3 cm in 74 cases), underwent CT guided percutaneous FANB with 22-gauge needle (in 84 cases) or 20-gauge needle (in 22 cases) by anterior approach. The biopsy sites included the head of pancreas and ampulla (n = 70), body of pancreas (n = 24), and tail of pancreas (n = 12). The key points of FANB included selection of appropriate cross-section, entry of needle, and multiple insertion in fan-like fashion with fast puncture and aspiration. Pathological examination was done to all biopsy specimens., Results: All lesions were safely accessed with an accuracy rate of 100% and without major complications. Pathological examination showed that 83 lesions were malignant, 5 of which were confirmed as false-positive, and 20 lesions were benign 2 of which were confirmed as false-negative, and 3 lesions were true-negative. The accuracy rates of diagnosis of malignant lesions and of diagnosis of benign lesion were 94% and 90% respectively (P > 0.05). The accuracy rate of diagnosis was 96% for the lesions >or= 3 cm was 96% and 88% for the lesions < 3 cm (P > 0.05). The accuracy rates of diagnosis were 93%, 92%, and 100% for the lesions located in the head of pancreas and ampulla of Vater, body of pancreas, and tail of pancreas (P > 0.05)., Conclusion: CT guided percutaneous FANB is a safe and effective method for the diagnosis and differential diagnosis of lesions in the pancreas.

Objective: To investigate the indications, key point, advantages, and disadvantages of transmaxillary approach for microsurgical removal of clivus tumors., Methods: The clinical data of 16 consecutive patients with clivus tumors operated upon through transmaxillary approach, based on Le Fort I ostectomy, July 1999 to May 2002 were retrospectively reviewed., Results: Of the 16 patients, 8 patients suffered from chordoma, 2 from angiofibroma, 1 from pituitary adenoma, 1 from chondroma, 1 from adenocarcinoma of grade II, 1 from mucoid cyst, 1 from myeloma, and 1 from fibrous dysplasia of bone. Four out of the 16 cases were with recurrent tumors after operation performed in other hospitals. The operation field of all 16 patients was satisfactorily exposed. The tumors of 10 cases were totally removed under microscope, and 6 tumors were subtotally removed. The complications included rhinorrhea in 1 case and malocclusion in 3 cases. There was no operative mortality. All patients were followed up for 6 approximately 40 months (ion average 20 months) with MRI. Four of them had local recurrence within 1 year, 1.5 years, 2 years, and 9 months respectively after operational and have lived with tumors till now. The remainders had resumed their normal life., Conclusion: An ideal approach, transmaxillary approach facilitates the resection of clivus tumors, with satisfying exposure and fewer complications.

We studied 97 patients who were diagnosed at the time of discharge having depressive neurosis within the period of 1984-1992. They were rediagnosed according to the diagnostic criteria of CCMD-2, dysthymia and mild degree of depression in ICD-10 and DSM-III-R. Only 23 patients were in accord with diagnostic criteria of CCMD-2 and maintained the diagnosis of depressive neurosis. The other 74 patients were diagnosed as having depression (single or recurrent episode) other types of neurosis, bipolar affective disorders (depressive phase or mixed phase) and schizophrenia. These diagnoses were similar to those in ICD-10 and DSM-III-R.