[Influence of visceral lipids obesity on the early postoperative complications after radical gastrectomy].

Objective: To investigate the effect of visceral fat area (VFA) on the surgical efficacy and early postoperative complications of radical gastrectomy for gastric cancer. Methods: A retrospective cohort study method was used. Clinicopathological data and preoperative imaging data of 195 patients who underwent D2 radical gastric cancer surgery at the First Affiliated Hospital of Xi'an Jiaotong University from January 2014 to December 2017 were analyzed retrospectively. Inclusion criteria: (1) complete clinicopathological and imaging data; (2) malignant gastric tumor diagnosed by preoperative pathology, and gastric cancer confirmed by postoperative pathology; (3) no preoperative complications such as bleeding, obstruction or perforation, and no distant metastasis. Those who had a history of abdominal surgery, concurrent malignant tumors, poor basic conditions, emergency surgery, palliative resection, and preoperative neoadjuvant therapy were excluded. The VFA was calculated by software and VFA ≥ 100 cm2 was defined as visceral obesity according to the Japan Obesity Association criteria . The patients were divided into high VFA (VFA-H, VFA≥100 cm2, n=96) group and low VFA (VFA-L, VFA<100 cm2, n=99) group . The clinicopathological characteristics, surgical outcomes and early postoperative complications were compared between the two groups. Univariate and multivariate Logistic regression models were used to analyze the risk factors of early complications. Receiver operating characteristic (ROC) curve was used to analyze predictive values of VFA for early complications. Pearson's χ2 test was used to analyze the correlation between BMI and VFA. Results: There were no significant differences in terms of gender, age, American Society of Anesthesiologists physical status classification, preoperative comorbidities, preoperative anemia, tumor TNM staging, N staging, T staging and tumor differentiation, surgical method, extent of resection, and tumor location between the VFA-L group and the VFA-H group (all P>0.05). However, patients in the VFA-H group had higher BMI, larger tumor, lower rate of hypoalbuminemia and greater subcutaneous fat area (SFA) (all P<0.05). The VFA-H group presented significantly longer operation time and significantly less number of harvested lymph nodes as compared to the VFA-L group (both P<0.05). However, there were no significant differences in intraoperative blood loss, conversion to laparotomy and postoperative hospital stay (all P>0.05). Complications of Clavien-Dindo grade II and above within 30 days after operation were mainly anastomosis-related complications (leakage, bleeding, infection and stricture), intestinal obstruction and incision infection. The VFA-H group had a higher morbidity of early complications compared to the VFA-L group [24.0% (23/96) vs 10.1% (10/99), χ2=6.657, P=0.010], and the rates of anastomotic complications and incision infection were also higher in the VFA group [10.4% (10/96) vs. 3.0% (3/99), χ2=4.274, P=0.039; 7.3% (7/96) vs. 1.0% (1/99), P=0.033]. Multivariate logistic analysis showed that high BMI (OR=3.688, 95%CI: 1.685-8.072, P=0.001) and high VFA (OR=2.526, 95%CI: 1.148-5.559,P=0.021) were independent risk factors for early complications. The area under the ROC curve (AUC) of VFA for predicting early complications was 0.645, which was higher than that of body weight (0.591), BMI (0.624) and SFA (0.626). Correlation analysis indicated that there was a significantly positive correlation between BMI and VFA (r=0.640, P<0.001). Conclusion: VFA ≥ 100 cm2 is an independent risk factor for early complications after radical gastrectomy for gastric cancer.It can better predict the occurrence of above early postoperative complications.

[Efficacy of laparoscopic proximal gastrectomy with double-tract reconstruction versus laparoscopic total gastrectomy with Roux-en-Y reconstruction for early upper gastric cancer].

Objective: To compare clinical efficacy between laparoscopic radical proximal gastrectomy with double-tract reconstruction (LPG-DTR) and laparoscopic radical total gastrectomy with Roux-en-Y reconstruction (LTG-RY) in patients with early upper gastric cancer, and to provide a reference for the selection of surgical methods in early upper gastric cancer. Methods: A retrospective cohort study method was carried out. Clinical data of 80 patients with early upper gastric cancer who underwent LPG-DTR or LTG-RY by the same surgical team at the Department of General Surgery, the First Affiliated Hospital of Xi'an Jiaotong University from January 2018 to January 2021 were retrospectively analyzed. Patients were divided into the DTR group (32 cases) and R-Y group (48 cases) according to surgical procedures and digestive tract reconstruction methods. Surgical and pathological characteristics, postoperative complications (short-term complications within 30 days after surgery and long-term complications after postoperative 30 days), survival time and nutritinal status were compared between the two groups. For nutritional status, reduction rate was used to represent the changes in total protein, albumin, total cholesterol, body mass, hemoglobin and vitamin B12 levels at postoperative 1-year and 2-year. Non-normally distributed continuous data were presented as median (interquartile range), and the Mann-Whitney U test was used for comparison between groups. The χ(2) test or Fisher's exact test was used for comparison of data between groups. The Mann-Whitney U test was used to compare the ranked data between groups. The survival rate was calculated by Kaplan-Meier method categorical, and compared by using the log-rank test. Results: There were no statistically significant differences in baseline data betweeen the two groups, except that patients in the R-Y group were oldere and had larger tumor. Patients of both groups successfully completed the operation without conversion to laparotomy, combined organ resection, or perioperative death. There were no significant differences in the distance from proximal resection margin to superior margin of tumor, postoperative hospital stay, time to flatus and food-taking, hospitalization cost, short- and long-term complications between the two groups (all P>0.05). Compared with the R-Y group, the DTR group had shorter distal margins [(3.2±0.5) cm vs. (11.7±2.0) cm, t=-23.033, P<0.001], longer surgery time [232.5 (63.7) minutes vs. 185.0 (63.0) minutes, Z=-3.238, P=0.001], longer anastomosis time [62.5 (17.5) minutes vs. 40.0 (10.0) minutes, Z=-6.321, P<0.001], less intraoperative blood loss [(138.1±51.6) ml vs. (184.3±62.1) ml, t=-3.477, P=0.001], with significant differences (all P<0.05). The median follow-up of the whole group was 18 months, and the 2-year cancer-specific survival rate was 97.5%, with 100% in the DTR group and 95.8% in the R-Y group (P=0.373). Compared with R-Y group at postoperative 1 year, the reduction rate of weight, hemoglobin and vitamin B12 were lower in DTR group with significant differences (all P<0.05); at postoperative 2-year, the reduction rate of vitamin B12 was still lower with significant differences (P<0.001), but the reduction rates of total protein, albumin, total cholesterol, body weight and hemoglobin were similar between the two groups (all P>0.05). Conclusions: LPG-DTR is safe and feasible in the treatment of early upper gastric cancer. The short-term postoperative nutritional status and long-term vitamin B12 levels of patients undergoing LPG-DTR are superior to those undergoing LTG-RY.

[Efficacy analysis of retroperitoneal laparoscopic selective renal artery branch occlusion and nephron sparing surgery for ≥ T1b stage renal carcinoma].

Objective: To investigate the safety and efficacy of retroperitoneal laparoscopic selective renal artery branch occlusion with nephron sparing surgery in patients with renal carcinoma of stage ≥ T1b. Methods: From July 2016 to September 2020, 35 patients with renal cancer ≥T1b underwent retroperitoneoscopic nephron sparing surgery in the First Affiliated Hospital of Shenzhen University. The surgical methods were retroperitoneoscopic nephron sparing surgery with total renal artery occlusion (group A) or selective renal artery branch occlusion (group B). Operation time, heat ischemia time, blood transfusion rate, positive margin rate, intraoperative blood loss, postoperative complications and length of hospital stay were compared between the two groups, and the total glomerular filtration rate (GFR) and the single-nephron glomerular filtration rate (sGFR) of the offected kidneys were compared between the two groups before, 3 months after and 12 months after surgery. Results: Among the 35 patients, 19 were male and 16 were female, aged (55.7±8.4) years and the body mass index is (24.6±3.1) kg/m2. The tumor diameter was (54.7±10.3) mm. The difference was statistically significant of operative time between group A and B [(103.5±14.3) vs (123.2±14.1) min,P=0.003]. There were no significant differences in thermal ischemia time, blood transfusion rate, positive margin, intraoperative blood loss, incidence of postoperative complications and length of hospital stay between the two groups (all P>0.05). The decrease of renal sGFR in the group A was significantly higher than group B at 3 months and 12 months after surgery [(23.1±3.6) vs (29.1±7.1) ml/min;(25.9±4.7) vs (30.7±7.2),both P<0.05]. Conclusion: Retroperitoneal laparoscopic selective renal artery branch occlusion and neon-sparing surgery for patients with ≥ T1b stage renal carcinoma is a safe and effective surgical method, which can well protect the renal function of patients in the early postoperative stage without increasing intraoperative blood loss and postoperative complications.

Macrophages promote cell proliferation in colorectal cancer via IL-1ß-mediated downregulation of miR-28-3p.

Infiltration of macrophages is associated with tumor progression and poor prognosis in multiple malignancies, but the underlying mechanisms by which macrophages contribute to colorectal cancer (CRC) have not yet been elucidated. The purpose of this study was to discuss the potential mechanisms of macrophages in CRC. The MTT assay was used to assess cell viability. The expression of the proliferation-related marker PCNA was detected by Western blot analysis. The 10 most important factors (PDGF, VEGF, TNFα, bFGF, IL-8, TGF-ß, IFN-γ, SPARC, IL-1ß and IL-6) secreted by macrophages were knocked down by RNA interference (RNAi), and the mRNA expression levels of these 10 factors were analyzed by qRT-PCR. The effect of these factors on cell proliferation was assessed by the MTT assay. The miRNAs regulated by IL-1ß in CRC cells were identified by miRNA microarray and qRT-PCR analyses. The proliferation ability of miR-28-3p inhibitor on CRC cells was detected by colony formation assay. The association of IL-1ß and miR-28-3p expression with the clinicopathological characteristics in patients with CRC was analyzed by TCGA RNA-seq data. As a result, macrophages promoted the proliferation of CRC cells in a time- and number-dependent manner, and these effects were associated with the upregulation of PCNA and the macrophage-secreted cytokine IL-1ß, which had the most significant effect on CRC cell proliferation. Furthermore, downregulation of miR-28-3p was induced by IL-1ß in CRC cells. The miR-28-3p inhibitor promoted the proliferation in CRC cells. Moreover, upregulation of IL-1ß expression or downregulation of miR-28-3p expression was associated with poor survival in patients with CRC. Therefore, these data demonstrated that macrophages promoted CRC cell proliferation via IL-1ß-mediated downregulation of miR-28-3p.

USP3 promotes proliferation of non-small cell lung cancer through regulating RBM4.

OBJECTIVE: Previous studies have shown that ubiquitin specific protease 3 (USP3) is an oncogene. However, the role of USP3 in non-small cell lung cancer (NSCLC) has not been reported. This study aims to explore the expression characteristics of USP3 in NSCLC, and its regulation on the proliferative capacity of NSCLC cells. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was performed to examine the expression levels of USP3 and RNA Binding Motif 4 (RBM4) in 42 pairs of tumor tissues and adjacent tissue specimens collected from NSCLC patients. Meanwhile, the correlation between the messenger ribonucleic acid (mRNA) expressions of USP3 and RBM4, and the clinical indicators and prognosis of NSCLC patients were analyzed. At the same time, mRNA expression of USP3 in NSCLC cell lines was further verified by the qRT-PCR method. In addition, USP3 knockdown and overexpression models were constructed using lentivirus in NSCLC cell lines H1299 and SPCA1. Cell counting kit-8 (CCK-8), cell colony formation, and 5-Ethynyl-2'-deoxyuridine (EDU) assays were performed to evaluate the influence of USP3 on proliferative capacity in NSCLC cells. Finally, Dual-Luciferase reporter assay and rescue experiments were conducted to further explore its underlying molecular mechanism. RESULTS: In this experiment, qRT-PCR results revealed that the expression level of USP3 in tumor tissues of NSCLC patients was remarkably higher than that in adjacent tissues, and the difference was statistically significant. Compared with NSCLC patients with low expression of USP3, those with high USP3 expression suffered much more advanced pathology stage and lower overall survival rate. Proliferation ability of NSCLC cells overexpressing USP3 was remarkably enhanced, while the opposite result was observed in the USP3 knockdown group. Subsequently, RBM4 expression in NSCLC tissue samples was found to be significantly reduced and negatively correlated with USP3 level. In addition, the result of Dual-Luciferase reporter assay demonstrated that USP3 can be targeted by RBM4. Rescue experiments revealed that RBM4 was responsible for NSCLC progression regulated by USP3. CONCLUSIONS: The above studies indicated that USP3 expression was remarkably up-regulated in NSCLC tissues, which was closely related to the pathological staging and poor prognosis of NSCLC patients. Therefore, USP3 might accelerate the proliferation of NSCLC cells via regulating RBM4.

[Semiquantitative parameters of 18F-FDG PET/CT, gene mutation states of epidermal growth factor receptor and anaplastic lymphoma kinase in prognosis evaluation of patients with lung adenocarcinoma].

OBJECTIVE: To explore the valuable predictors for evaluating progression-free survival (PFS) in patients with lung adenocarcinoma, we analyzed the potential roles of standardized uptake value (SUV)-derived parameters from 18F-FDG PET/CT, combining with the gene mutation states of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), and other clinical characteristics. METHODS: Data of 84 lung adenocarcinoma patients pre-treated, who underwent 18F-FDG PET/CT scans, EGFR gene mutations test, ALK rearrangement assay and other relative tests, were retrospectively collected. Then a series of clinical parameters including EGFR/ALK mutation status and SUV-derived features [maximum standardized uptake value (SUVmax), average of standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)] were evaluated. Best possible cutoff points for all measuring parameters were calculated using receiver operating characteristic curve (ROC) analysis. Survival analysis was performed using Cox proportional hazards model to determine the prognostic markers for progression-free survival (PFS). Survival curves were obtained through Log-rank test and Kaplan-Meier curve. RESULTS: The median follow-up period was 31 months (24 to 58 months). It was found that SUVmax (≥3.01), SUVmean (≥2.25), MTV (≥25.41 cm3), and TLG (≥55.02) of the primary tumors were significantly associated with PFS in univariate Cox proportional hazards regression. Then regardless of age, gender, co-morbidity, EGFR/ALK mutation status, and treatment program, TLG (≥ 55.02, HR=4.965, 95%CI: 1.360-18.133), TNM stage (Ⅲ/Ⅳ, HR=7.811, 95%CI: 2.977-20.489), pro-gastrin releasing peptide (proGRP) (≥45.65 ng/L, HR=4.070, 95%CI: 1.442-11.487), tissue polypeptide antigen (TPA) (≥68.20 U/L, HR=6.996, 95%CI: 1.458-33.574), alkaline phosphatase (ALP) (≥82.50 IU/L, HR=4.160, 95%CI: 1.416-12.219) and ratio of activated partial thromboplastin time (aPTTR) (≥1.16: HR=4.58, 95%CI: 1.913-10.946) showed the independently relevant to PFS through multivariate Cox proportional hazards analysis. The EGFR mutant (P=0.343) and ALK rearrangement (P=0.608) were not significant either in survival analysis. CONCLUSION: High SUV-derived parameters (SUVmax, SUVmean, MTV and TLG) might provide prognostic value to some extent. Especially, TLG, and other clinical features [TNM stage, proGRP, TPA, ALP, and aPTTR] could be independently and significantly associated with PFS of lung adenocarcinoma patients. However, EGFR/ALK gene status could not be effectively relevant to PFS in lung adenocarcinoma patients.

MiRNA-500a-3p inhibits cell proliferation and invasion by targeting lymphocyte antigen 6 complex locus K (LY6K) in human non-small cell lung cancer.

LY6K (lymphocyte antigen 6 complex locus K) is an anti-gene in non-small cell lung cancer (NSCLC) and miR-500a-3p promotes the progression of cancers. Evidence shows that the increase of miR-500a-3p caused LY6K to be suppressed. Here we hypothesized that miR-500a-3p may take part in the progression of NSCLC through targeting LY6K. miR-500a-3p expression levels in NSCLC specimens and cell lines were detected by quantitative real-time PCR (qRT-PCR). The mRNA and protein expression levels of LY6K in NSCLC specimens and cell lines were examined by qRT-PCR, immunohistochemistry and western blotting. Dual-luciferase reporter assay was carried out to assess miR-500a-3p binding to LY6K gene. The functions of miR-500a-3p and LY6K in proliferation/invasion and lung metastasis formation were assessed by CCK8, Transwell assay and subcutaneous tumor model in nude mice, respectively. Statistical analysis was performed to explore the clinical correlation between miR-500a-3p/LY6K expression and clinicopathological features. miR-500a-3p was substantially decreased in NSCLC tissues and cell lines. LY6K protein and mRNA level expressions were increased in NSCLC patients. Clinical analysis indicated that miR-500a-3p and LY6K were related to tumor differentiation, lymph node metastasis and TNM staging in NSCLC patients. MiR-500a-3p suppresses cell proliferation, invasion and metastasis formation in vivo by targeting the LY6K. miR-500a-3p acts as a tumor suppressor in NSCLC partially via down-regulation of LY6K expression and for NSCLC intervention and suggests a potential therapeutic target for NSCLC intervention.

The Roles of the Unique Prolyl Isomerase Pin1 in Cancer-Related Viral and Bacterial Infections.

Infection is the process of pathogen invasion, as well as the host reaction to the foreign agents. Proline-directed phosphorylation is a major regulatory mechanism that regulates the function of fundamental proteins involved in infection and infection-induced cancer. Recently, the identification of the phosphorylation-dependent prolyl isomerase Pin1 has uncovered a unique regulatory signaling mechanism controlling protein conformation and function after phosphorylation. Pin1 is the only proline isomerase that specifically recognizes certain Pro-directed Ser/Thr phosphorylation motifs. Pin1 has emerged as a major regulator of cancerrelated viral and bacterial infections notably via activating Toll-like receptor signaling and NF-κB pathways. This paper will specifically review recent findings on the role of Pin1 in cancer-related viral and bacterial infections and also discuss newly discovered Pin1 inhibitors as promising drugs for the prevention and treatment of viral and bacterial infections and associated tumorigenesis.

Long intergenic non-coding RNA APOC1P1-3 inhibits apoptosis by decreasing α-tubulin acetylation in breast cancer.

Increasing evidence indicates that long non-coding RNAs (lncRNAs) act as important regulatory factors in tumor progression. However, their roles in breast cancer remain largely unknown. In present studies, we identified aberrantly expressed long intergenic non-coding RNA APOC1P1-3 (lincRNA-APOC1P1-3) in breast cancer by microarray, verified it by quantitative real-time PCR, and assessed methylation status in the promoter region by pyrosequencing. We also investigated the biological functions with plasmid transfection and siRNA silencing experiments, and further explored their mechanisms by RNA pull-down and RNA immunoprecipitation to identify binding proteins. We found that 224 lncRNAs were upregulated in breast cancer, whereas 324 were downregulated. The lincRNA-APOC1P1-3 was overexpressed in breast cancer, which was related to tumor size and hypomethylation in its promoter region. We also found that APOC1P1-3 could directly bind to tubulin to decrease α-tubulin acetylation, to inactivate caspase-3, and to inhibit apoptosis. This study demonstrates that overexpression of APOC1P1-3 can inhibit breast cancer apoptosis.

Hematopoietic Stem Cells Transplantation Can Normalize Thyroid Function in a Cystinosis Mouse Model.

Hypothyroidism is the most frequent and earliest endocrine complication in cystinosis, a multisystemic lysosomal storage disease caused by defective transmembrane cystine transporter, cystinosin (CTNS gene). We recently demonstrated in Ctns(-/-) mice that altered thyroglobulin biosynthesis associated with endoplasmic reticulum stress, combined with defective lysosomal processing, caused hypothyroidism. In Ctns(-/-) kidney, hematopoietic stem cell (HSC) transplantation provides long-term functional and structural protection. Tissue repair involves transfer of cystinosin-bearing lysosomes from HSCs differentiated as F4/80 macrophages into deficient kidney tubular cells, via tunneling nanotubes that cross basement laminae. Here we evaluated the benefit of HSC transplantation for cystinotic thyroid and investigated the underlying mechanisms. HSC engraftment in Ctns(-/-) thyroid drastically decreased cystine accumulation, normalized the TSH level, and corrected the structure of a large fraction of thyrocytes. In the thyroid microenvironment, HSCs differentiated into a distinct, mixed macrophage/dendritic cell lineage expressing CD45 and major histocompatibility complex II but low CD11b and F4/80. Grafted HSCs closely apposed to follicles and produced tunneling nanotube-like extensions that crossed follicular basement laminae. HSCs themselves further squeezed into follicles, allowing extensive contact with thyrocytes, but did not transdifferentiate into Nkx2.1-expressing cells. Our observations revealed significant differences of basement lamina porosity between the thyroid and kidney and/or intrinsic macrophage invasive properties once in the thyroid microenvironment. The contrast between extensive thyrocyte protection and low HSC abundance at steady state suggests multiple sequential encounters and/or remanent impact. This is the first report demonstrating the potential of HSC transplantation to correct thyroid disease and supports a major multisystemic benefit of stem cell therapy for cystinosis.

Contrast-enhanced transrectal ultrasonography for the detection of diffuse prostate cancer.

AIM: To evaluate the diagnostic accuracy of contrast-enhanced transrectal ultrasonography (CE-TRUS) versus baseline TRUS (combination of grey-scale and colour Doppler imaging) for diffuse prostate cancer. MATERIALS AND METHODS: Forty-six patients without an obvious focal mass on baseline TRUS (grey-scale and colour Doppler), underwent additional CE-TRUS and TRUS-guided biopsy due to elevated levels of prostate-specific antigen (PSA ≥4 ng/ml) and/or abnormal digital rectal examination (DRE). In all patients, CE-TRUS was performed with intravenous injection of a contrast agent (sulphur hexafluoride microbubble; SonoVue, 2.4 ml) before biopsy. TRUS-guided biopsy targeted suspicious areas detected on CE-TRUS imaging or sampled the outer gland of the normal prostate. The final diagnosis was based on results of the TRUS-guided biopsy. The diagnostic accuracy of baseline TRUS and CE-TRUS for diffuse prostatic lesions was evaluated using receiver operating characteristic (ROC) curve analysis. RESULTS: Diffuse prostate cancer was present in 32 (69.5%) patients and absent in 14 (30.5%) patients. Nineteen patients had diffuse prostate cancer that was not detected by baseline TRUS, whereas 15 cases were identified using CE-TRUS. Conversely, five patients had benign prostatic hypertrophy (BPH) that was diagnosed as cancer by CE-TRUS, and two of these patients were diagnosed with BPH by baseline TRUS. The combined sensitivity, specificity, and accuracy were 87.5%, 64.2%, and 80.4%, respectively, for CE-TRUS, and 40.6%, 78.5%, and 52.1%, respectively, for baseline TRUS. The area under the ROC curve (AUC) values for the diagnostic accuracy of baseline CE-TRUS versus TRUS for diffuse prostate cancer differed significantly at 0.904 and 0.667, respectively (Z=4.098, p<0.0001). CONCLUSION: CE-TRUS exhibited greater diagnostic accuracy for diffuse prostate cancer than baseline TRUS. CE-TRUS may improve cancer detection over baseline TRUS imaging for the diagnosis of diffuse prostate cancer in patients with an elevated PSA level. CE-TRUS detects diffuse prostate cancer without an obvious focal mass on routine TRUS or clinical examination, and therefore, may help identify patients who do not need a repeat biopsy or who do not need to undergo systematic 12-core invasive sampling biopsies.

A mouse model suggests two mechanisms for thyroid alterations in infantile cystinosis: decreased thyroglobulin synthesis due to endoplasmic reticulum stress/unfolded protein response and impaired lysosomal processing.

Thyroid hormones are released from thyroglobulin (Tg) in lysosomes, which are impaired in infantile/nephropathic cystinosis. Cystinosis is a lysosomal cystine storage disease due to defective cystine exporter, cystinosin. Cystinotic children develop subclinical and then overt hypothyroidism. Why hypothyroidism is the most frequent and earliest endocrine complication of cystinosis is unknown. We here defined early alterations in Ctns(-/-) mice thyroid and identified subcellular and molecular mechanisms. At 9 months, T4 and T3 plasma levels were normal and TSH was moderately increased (∼4-fold). By histology, hyperplasia and hypertrophy of most follicles preceded colloid exhaustion. Increased immunolabeling for thyrocyte proliferation and apoptotic shedding indicated accelerated cell turnover. Electron microscopy revealed endoplasmic reticulum (ER) dilation, apical lamellipodia indicating macropinocytic colloid uptake, and lysosomal cystine crystals. Tg accumulation in dilated ER contrasted with mRNA down-regulation. Increased expression of ER chaperones, glucose-regulated protein of 78 kDa and protein disulfide isomerase, associated with alternative X-box binding protein-1 splicing, revealed unfolded protein response (UPR) activation by ER stress. Decreased Tg mRNA and ER stress suggested reduced Tg synthesis. Coordinated increase of UPR markers, activating transcription factor-4 and C/EBP homologous protein, linked ER stress to apoptosis. Hormonogenic cathepsins were not altered, but lysosome-associated membrane protein-1 immunolabeling disclosed enlarged vesicles containing iodo-Tg and impaired lysosomal fusion. Isopycnic fractionation showed iodo-Tg accumulation in denser lysosomes, suggesting defective lysosomal processing and hormone release. In conclusion, Ctns(-/-) mice showed the following alterations: 1) compensated primary hypothyroidism and accelerated thyrocyte turnover; 2) impaired Tg production linked to ER stress/UPR response; and 3) altered endolysosomal trafficking and iodo-Tg processing. The Ctns(-/-) thyroid is useful to study disease progression and evaluate novel therapies.

Fertility clinicians and infertile patients in China have different preferences in fertility care.

STUDY QUESTION: Do the preferences for fertility care of infertile Chinese patients differ from those of fertility care providers? SUMMARY ANSWER: Infertile Chinese patients attached the greatest importance to physicians' attitude but, in contrast, fertility care providers in China considered treatment effectiveness to be the most important factor in fertility care. WHAT IS KNOWN ALREADY: In Europe, physicians underestimate the importance of patient-centred infertility care. STUDY DESIGN, SIZE, DURATION: A conjoint survey was distributed among 417 female infertile Chinese patients and 83 fertility care providers from February 2013 to August 2013. PARTICIPANTS/MATERIALS, SETTING, METHODS: In this pilot study, 389 patients and 83 fertility care providers completed the survey at three reproductive medicine centres. Rating-based conjoint analysis was performed to elicit patients' and their caregivers' preferences regarding fertility care. Cluster analysis was used to explore the heterogeneity among patients' preferences. MAIN RESULTS AND THE ROLE OF CHANCE: When searching for fertility care, patients valued the physicians' attitude the most, followed by success rates, distance from home to the fertility centre, physician continuity throughout the treatment period and type of fertility centre. Fertility care providers considered success rates (effectiveness) to be the most important factor when recommending a fertility centre. Fertility patients and care providers had significantly different views on the value of treatment effectiveness, physician attitude and physician continuity (P-values <0.05). Cluster analysis revealed that patients' preferences were heterogeneous. LIMITATIONS, REASONS FOR CAUTION: The sample size is relatively small, and there is insufficient power for heterogeneity analysis. Two levels for each of five design factors (2(5)) may not fully capture the characteristics of realistic fertility centres. Rating-based conjoint analysis could be inferior to choice-based conjoint analysis in terms of predictive accuracy. WIDER IMPLICATIONS OF THE FINDINGS: Fertility care providers in China significantly underestimate the importance of patient-centredness to infertile patients. To deliver optimal fertility care to infertile Chinese patients, fertility care providers need to understand the importance of patient-centred care, such as a friendly attitude, sympathy for patients' suffering, respect for patients' right to informed consent and a transparent treatment process. STUDY FUNDING/COMPETING INTEREST(S): This study was not funded, and there are no conflicts of interest. TRIAL REGISTRATION NUMBER: None.

A case of renal γ2 heavy-chain deposition disease accompanied by rapid progressive renal failure.

BACKGROUND: The recently described heavy-chain deposition disease (HCDD) is a comparatively rare monoclonal immunoglobulin disorder characterized histopathologically by glomerular and tubular basement membrane deposition of nonamyloidotic monoclonal heavy chains without associated light chains. METHOD: We have described a case of γ2-HCDD presenting with proteinuria, microhematuria, severe hypertension, and rapidly progressive renal failure, which serum creatinine level was only 1.52 mg/dL in early stage HCDD, and the clinicopathologic features of this case have been compared with other reported cases of γ2-HCDD. RESULTS: Renal biopsy disclosed nodular sclerosing glomerulopathy. Immunofluorescence analysis revealed IgG2 (2+) heavy chain and C3 (+) in the mesangium and along the capillary walls and tubular basement membranes without IgA, IgM, κ and λ light chains. Electron microscopy revealed electron-dense deposits along the glomerular and tubular basement membranes as well as in the mesangium. Moreover, regardless of therapy, the condition of the patient progressively deteriorated, with less than 3 months of renal survival. CONCLUSION: Rapid progressive renal failure was a common feature in both cases of γ2-HCDD. We propose that a possible link exists between prognosis of renal HCDD and the subclass of heavy chain deposited in the kidney.

Reduction in interval cancer rates following the introduction of two-view mammography in the UK breast screening programme.

BACKGROUND: The introduction of two-view mammography at incident (subsequent) screens in the National Health Service Breast Screening Programme (NHSBSP) has led to an increased number of cancers detected at screen. However, the effect of two-view mammography on interval cancer rates has yet to be assessed. METHODS: Routine screening and interval cancer data were collated from all screening programmes in the United Kingdom for women aged 50-64, screened between 1 April 2003 and 31 March 2005. Interval cancer rates were compared based on whether two-view mammography was in use at the last routine screen. RESULTS: The reduction in interval cancers following screening using two-view mammography compared with one view was 0.68 per 1,000 women screened. Overall, this suggests the introduction of two-view mammography at incident screen was accompanied by a 15-20% reduction in interval cancer rates in the NHSBSP. CONCLUSION: The introduction of two-view mammography at incident screens is associated with a reduction in incidence of interval cancers. This is consistent with previous publications on a contemporaneous increase in screen-detected cancers. The results provide further evidence of the benefit of the use of two-view mammography at incident screens.

Cross-talk between PI3K and estrogen in the mouse thyroid predisposes to the development of follicular carcinomas with a higher incidence in females.

It is well known that thyroid disease is more frequent in women than in men; however, the molecular basis for this gender-based difference is still poorly understood. The activation of phosphoinositide 3-kinase (PI3K), through different mechanisms including loss of the PTEN tumor suppressor, is being increasingly recognized as a major player in the development of thyroid neoplastic lesions. Loss of Pten in the mouse thyroid results in a significant increase in the thyrocyte proliferative index, which is more prominent in the female mice. In this study, we show that 52% of the Pten(-/-) female mice, but only 12% of the males, develop follicular adenomas by 1 year of age. In addition, 50% of female mutants, but only 35% of males older than 1 year of age develop invasive, and often metastatic, follicular carcinomas. Mutant females have a significantly shorter overall survival compared with male mutants. Hormonal manipulation experiments established a direct role of estrogens in controlling the increased thyrocyte proliferation index in mutant females. Furthermore, while genetic ablation of one Cdkn1b allele accelerated the development of neoplastic lesions, it also abolished the gender differences in survival and reduced the difference in neoplastic lesion development rate, underlining a key role of p27 in mediating estrogen action in the thyroid follicular cells. These data, based on a clinically relevant model of thyroid follicular carcinoma, provide, to the best of our knowledge, for the first time in vivo evidence that circulating estrogens are directly responsible for the increased female susceptibility to thyroid disease, at least on activation of the PI3K pathway, and provide new insights into the gender-based differences characterizing thyroid neoplastic disorders.

The management of venous leg ulcers: a project to improve care.

This article describes a two-year project to develop resources for the improvement of leg ulcer management. It was felt that an audit tool and complementary resources, such as a resource pack and implementation guide, could help practitioners to implement clinical guidelines on leg ulcer management in practice. The audit results from the pilot project are briefly described and discussed in terms of informing future work.

[Preparation and qualitative control of compound Dyclonine's suspending mixture].

The paper deals with the composition, preparation and qualitative control of compound Dyclonine's suspending mixture, one of gastroscopic mucomembranous anesthetics. The content of Dyclonine hydrochloride was detected by ultraviolet spectrophotometry. It shows that the average rate of recovery is 100.80%, RSD = 1.32%(n = 6). At room temperature, the appearance and content of the preparation are not changed in 0, 30, 180, 365 days respectively. The preparation is widely and successfully used in clinics with easy procedure and excellent stability.