[Construction of a nomogram model for predicting 2-year survival rate of small cell lung cancer based on more comprehensive variables].

Objective: To construct a novel prognostic nomogram model based on more comprehensive variables for patients with small-cell lung cancer (SCLC). Methods: The data of 722 patients with SCLC confirmed by pathology in Affiliated Cancer Hospital of Shanxi Medical University from January 2015 to December 2018 were retrospectively analyzed [including 592 males and 130 females, aged from 23 to 82(61±9) years]. A random seed count of 133 was used to divide those patients into training set (n=422) and validation set (n=300). Kaplan-Meier was used for survival curves analysis and univariate Log-rank test was used for evaluating the influence of clinical variables on the prognosis of sclc, variables with P<0.05 in univariate analysis were included in a multivariate Cox regression model. The nomogram was constructed based on the variables which P<0.05 in multivariate analysis. Receiver operating characteristic (ROC) curve, calibration by Integrated Brier score (IBS) and clinical net benefit by decision curve analysis (DCA) were used to evaluate model discriminative power, prediction error value, and clinical net benefit, and compared with the American Joint Committee on Cancer 8th TNM. Results: Male, abnormal monocyte (MON) counts, abnormal neuron specific enolase (NSE), abnormal cytokeratin 19 fragment (Cyfra211), M1a stage, M1b stage, M1c stage, radiotherapy (RT), chemotherapy ≥4 cycles and prophylactic cranial irradiation (PCI) were prognostic factors for SCLC[HR(95%CI)=1.39(1.00-1.92), 1.29(1.02-1.63), 1.41(1.11-1.80), 2.02(1.48-2.76), 1.09(0.77-1.55), 1.44(0.94-2.22), 2.01(1.49-2.71), 0.75(0.57-0.98), 0.40(0.31-0.51)and 0.42(0.26-0.68), respectively, all P<0.05]. The area under ROC curve (AUC) of the nomogram in training set and validation set were 0.814(95%CI: 0.765-0.862)and 0.787 (95%CI: 0.725-0.849), which were higher than TNM [0.616(95%CI: 0.558-0.674) and 0.648(95%CI: 0.581-0.715)].The calibration curve showed a good correlation between the nomogram prediction and actual observation for the 2-year overall survival (OS). IBS indicted a lower prediction error rate (training set: 0.132 vs 0.169; validation set: 0.138 vs 0.169). DCA showed a wider threshold range than TNM (training set: 0.01-0.96 vs 0.01-0.85, validation set: 0.01-0.94 vs 0.01-0.86) and a greater improvement of the clinical net benefit (in training set the nomogram had a greater clinical benefit than TNM in the range of 0.19-0.96, and remained in validation set in the range of 0.19-0.94). Conclusion: The established nomogram model for predicting 2-year OS in patients with SCLC based on 8 variables, including gender, MON, NSE, Cyfra211, M stage, RT, CT cycles and PCI can be used for an more accurately prognosis prediction and reference for therapeutic regimen selection.

[Mismatch repair protein expression of colorectal cancer: a retrospective analysis of 3 428 cases].

Objective: To analyze the expression of mismatch repair (MMR) proteins in colorectal cancers (CRC) and to evaluate the feasibility and potential pitfalls of immunohistochemistry (IHC) analysis for MMR. Methods: The IHC sections for MMR proteins were reviewed in 3 428 cases of resected CRC without neoadjuvant therapy at Tianjin Medical University Cancer Institute and Hospital from July 2014 to October 2018. For the cases with unclear MMR IHC results during the initial review, IHC staining was repeated and microsatellite instability (MSI) analysis was performed. Relationships between the expression of MMR proteins and MSI status as well as the clinicopathological parameters were analyzed. Results: IHC staining for MMR was repeated in 28 (0.8%) cases due to poor quality of original IHC sections. Inconsistent results between the original diagnosis and re-diagnosis were found in 119 (3.5%) cases, mainly resulting from PMS2 and MLH1. Finally, 261 (7.6%) cases of CRC showed mismatch repair deficiency (dMMR), mainly from the deficiency of both MLH1 and PMS2 (43.3%,113/261). In the 14 cases with MSI results, the concordant of MSI and MMR was 13 cases. In the 29 dMMR cases with next generation sequencing (NGS) results, the concordant of MSI-high and dMMR was 93.1%(27/29). The cases with inconsistent results between MSI and MMR showed negative expression of MSH6 or PMS2. Twenty-one CRC showed negative expression of MLH1 and partially positive (or weak positive) expression of PMS2, or negative expression of MSH2 and partially positive (or weak positive) expression of MSH6. Among the 19 cases with MSI results, 16 cases were MSI-high, two cases were MSI-low, and one case was microsatellite stable. Compared with mismatch repair proficiency (pMMR), dMMR was more frequently detected in female patients younger than 50 years old, with family history, at early stage (Ⅰ-Ⅱ) CRC, and in the tumors from right colon,with poor differentiation, or mucinous adenocarcinoma/signet ring cell carcinoma (all P<0.05). Conclusions: At present, IHC staining is a clinically effective and convenient method to detect MMR expression, but the operating process and result assessment remain variable and need to be standardized. MSI analysis can be performed in the difficult-to-evaluate cases for MMR to enhance prognostic evaluation and treatment option.

[Clinical application of LDLT after reconstruction of IVC using artificial blood vessel in the treatment of HCC beyond Milan Criteria].

Objective: To assess application of reconstruction of retrohepatic inferior vena cava using artificial blood vessel in right lobe living donor liver transplantation (LDLT) in the treatment of hepatocellular carcinoma (HCC) beyond Milan Criteria. Methods: The clinical data of 9 HCC patients who underwent right lobe liver transplantation after reconstruction of retrohepatic inferior vena cava using artificial blood vessel between June 2015 and Nov 2016 at Liver Transplantation Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed. The liver of the patients was removed with retrohepatic inferior vena cava, and then the right donor graft was implanted by conventional orthotopic liver transplantation. Results: All 9 liver transplantations were performed successfully. The time of reconstruction of hepatic venous outflow of the donor graft was (22.6±3.0) min, anhepatic time was (45.0±7.1) min, and total operation time was (321.9±52.5) min. All patients recovered uneventfully, ICU and hospital stay day were (1.2±0.4) days and (18.4±3.0) days. 2 patients suffered from thrombosis of artificial blood vessel, one recovered after conservative treatment and another was treated by placement of vein stent. No abdominal/pulmonary infection and non-artificial blood vascular complications were found, and none died in perioperative period. Postoperative pathological results showed that all patients were hepatocellular carcinomas and vascular tumor thrombosis was found in 5 cases. All patients were follow up, 1 patient died of pulmonary and brain metastasis 10 months after operation. One patient survived with local recurrence of tumor in liver. The other patients had no tumor recurrence and metastasis. Conclusion: Replacement of retrohepatic inferior vena cava using artificial blood vessel in right lobe living donor liver transplantation is safe and feasible in the treatment of HCC beyond Milan Criteria, and might improve the resection rate of diseased liver and the prognosis of HCC patients after living donor liver transplantation.

[Expression of stem cell markers CD44 and Lgr5 in colorectal cancer and its relationship with lymph node and liver metastasis].

Objective: To investigate the relationship between the expression of stem cell markers CD44 and Lgr5 and the clinicopathological features, lymph node and liver metastasis, and to analyse the value of both in evaluating the prognosis of colorectal cancer. Methods: A total of 90 cases of colorectal cancer, 20 cases of adjacent tissues, 30 cases of lymph node metastases, 28 cases of cancer nodules and 30 cases of liver metastasis of colorectal cancer were collected from Department of Pathology of the Second Hospital of Tianjin Medical University from January 2011 to June 2016. The expression of CD44 and Lgr5 protein was detected by immunohistochemistry, and the relationship between them and clinical pathological data, lymph node metastasis and liver metastasis were analyzed. Results: The positive expression rates of CD44 and Lgr5 in colorectal cancer tissues were 68.9% and 62.2%, which were significantly higher than 30.0% and 15.0% of adjacent tissues(P=0.001 and P<0.001). The expression of CD44 and Lgr5 in colorectal cancer was associated with histological differentiation, depth of tumor invasion, lymph node metastasis, soft tissue nodules, hepatic metastasis, and TNM staging(P=0.021, 0.032, 0.030, 0.011, 0.015, 0.007 and P=0.011, 0.027, 0.017, 0.008, 0.011, 0.021). The positive rates of CD44 and Lgr5 expression in lymph node metastases, cancer nodules and liver metastases (93.3%, 89.3%, 90.0%, and 83.3%, 89.3%, 86.7%) were higher than those in the primary lesions(68.9% and 62.2%)(P=0.007, 0.032, 0.022 and P=0.033, 0.007, 0.013). There is a positive correlation between the expression of CD44 and Lgr5 in colorectal cancer(r=0.615, P<0.001), and both positive expression of CD44 and Lgr5 is associated with histological differentiation, lymph node metastasis and cancer nodules, liver metastasis and TNM staging(P=0.005, 0.003, 0.003, 0.026, 0.014). The Kaplan-Meier survival curve showed that the survival rate of positive expression of CD44 and both positive expression of CD44 and Lgr5 in patients with colorectal cancer was low(P=0.030 and 0.001). Log-rank univariate survival analysis showed that histological differentiation, depth of invasion, lymph node metastasis, liver metastasis, and clinical stage were the influencing factors of postoperative survival time(P=0.035, 0.035, 0.018, 0.016, 0.004). Cox proportional hazards regression model multivariate analysis showed that both positive expression of CD44 and Lgr5, lymph node metastasis, liver metastasis, and clinical stage were independent factors affecting the prognosis of patients with colorectal cancer(P=0.004, 0.044, 0.031, 0.008). Conclusions: The expression of CD44 and Lgr5 is related to the malignant biological behavior of colorectal cancer, and they are important factors in promoting local and distant metastases. Both positive expression of them have a hint of bad prognosis.

[Expression and prognostic significance of microenvironment related prognostic factors in patients with classical Hodgkin's lymphoma].

Objective: To observe the expression of three microenvironment related prognostic factors, i. e. programmed death 1 (PD-1), forkhead box protein 3(FOXP3) and colony-stimulating factor 1 receptor(CSF-1R) protein in classical Hodgkin's lymphoma (CHL) patients, and to explore the correlation between the protein expression and the prognosis of the patients. Methods: A total of 45 cases of CHL patients, who had been admitted to the Tianjin Medical University Cancer Institute and Hospital and Chinese PLA General Hospital from February 2005 to August 2010 were analyzed, including clinical features, prognostic factors, and treatment regimens. CHL patients' specimens were collected and the expression of PD-1, FOXP3, and CSF-1R proteins analyzed by immunohistochemical staining. Epstein-Barr virus encoded mRNA (EBER) was detected by in situ hybridization analysis. The relationship between the protein expression of PD-1, FOXP3 and CSF-1R and the patients' outcome was analyzed with clinical and follow-up data. Survival analysis was performed by Kaplan-Meier method, the Cox proportional hazard model was used to perform multivariate analysis. Results: In this cohort of 45 CHL patients, PD-1 positive was found in 7 cases (15.6%), FOXP3 high expression in 23 cases (51.1%), CSF-1R positive in 18 cases (40.0%). In the univariate analysis, the expression of FOXP3 and CSF-1R, International Prognostic Index (IPI) score, Ann Arbor stage and EBER were related with the patients' 5-year overall survival (OS); IPI score, the expression of FOXP3 and EBER were related with the patients' 5-year progress-free survival (PFS). Multivariate analysis indicated that CSF-1R protein expression was the independent prognostic factor affecting the patients' 5-year OS(HR: 8.918, P=0.020), and FOXP3 protein expression was the independent prognostic factor affecting the patients' 5-year PFS (HR: 0.122, P<0.001). And EBV was an independent prognostic factor of PFS and OS in the CHL patients. Conclusion: Microenvironment related prognostic factors FOXP3, CSF-1R and EBV may be independent prognostic factors of CHL and this study may provide novel strategies for targeted therapy of CHL.

[Effect of CCR1 gene overexpression on the migration of bone marrow - derived mesenchymal stem cells towards hepatocellular carcinoma].

Objective: To evaluate the effect of human CCR1 (hCCR1) gene overexpression on the migration of human bone marrow-derived mesenchymal stem cells (hMSCs) towards hepatocellular carcinoma (HCC), and to examine the application prospects of MSCs as gene delivery vectors in the treatment of HCC. Methods: The hCCR1 gene was subcloned into a lentiviral vector to generate the recombinant plasmid pLV-hCCR1. The pLV-hCCR1 plasmid and two other packaging plasmids were co-transfected into 293T cells using calcium phosphate, and the virus-containing supernatant was collected. hMSCs were then infected with the recombinant lentivirus, and the expression of hCCR1 mRNA and protein was analyzed by RT-PCR and Western blot, respectively. The effect of CCR1 gene overexpression on the in vitro migration of hMSCs was examined using the Transwell migration assay. Orthotopic nude mice models of HCC were established using the MHCC-97H-GFP cell line, and the mice were divided into two groups (n = 8 per group). hMSCs were then intravenously injected via the tail vein into the tumor-bearing nude mice to examine the effect of hCCR1 overexpression on the in vivo migration of hMSCs towards HCC. Unpaired Student's t-test was used for two-group comparisons, and one-way ANOVA was used for multi-group comparisons. Results: Restriction enzyme digestion and DNA sequencing demonstrated that the recombinant plasmid pLV-hCCR1 was constructed successfully. The LV-hCCR1 lentivirus packaged by 293T cells has high infection efficiency in hMSCs, and hCCR1 was overexpressed in hMSCs after LV-hCCR1 infection. Transwell migration assay showed that hCCR1-transfected hMSCs had significantly enhanced migration towards HCC cell line-derived condition medium (CM) compared with the control RFP-hMSCs [(134.8±15.7)/LPF vs (83.5±10.9)/LPF, t = 10.40, P < 0.01]. In vivo migration experiment also demonstrated that there was significantly higher number of hCCR1-hMSCs localized within the MHCC-97H-GFP xenografts than hMSCs-RFP on day 14 following intravenous injection of hMSCs in mice [(86.7±14.1)/HPF vs (54.5±9.6)/HPF, t = -7.32, P < 0.01]. Conclusion: Overexpression of CCR1 gene can significantly enhance the migration capacity of hMSCs towards HCC cells in vitro and in vivo. This study provides evidence for potential clinical application of MSCs as more effective delivery vehicles in cancer gene therapy.

[Evaluate the prevalence of trachoma in high risk area of China].

OBJECTIVE: To determine the prevalence of trachoma in urban and rural area in China. To provide the data evidence for the strategies of eliminating trachoma in China. METHODS: Survey was conducted in 13 suspect trachoma high prevalence provinces according to the World Health Organization trachoma grading system and Trachoma Rapid Assessment(TRA). RESULTS: From 2004 to 2007, a total number of examined children which were younger than 10 years old was 59 630. The prevalence of TF was 0.94%. To sum up the data of 2004 and 2005, the prevalence of active trachoma was 1.71% for children.TT and CO was not reported. The results for subjects older than 50 years old showed that the prevalence of TT was 0.34%. We examined 26 857 adults in both 2004 and 2005.The prevalence of TF, TI, TS and CO was 0.03%,0.08%,0.88% and 0.05% respectively. CONCLUSIONS: The prevalence of active trachoma of younger children was under 5%. However,the prevalence of TT of the adults was not reached the target.

Genetic differentiation of Octopus minor (Mollusca, Cephalopoda) off the northern coast of China as revealed by amplified fragment length polymorphisms.

Octopus minor (Sasaki, 1920) is an economically important cephalopod that is found in the northern coastal waters of China. In this study, we investigated genetic differentiation in fishery populations using amplified fragment length polymorphisms (AFLPs). A total of 150 individuals were collected from five locations: Dalian (DL), Yan-tai (YT), Qingdao (QD), Lianyungang (LY), and Zhoushan (ZS), and 243 reproducible bands were amplified using five AFLP primer combinations. The percentage of polymorphic bands ranged from 53.33 to 76.08%. Nei's genetic identity ranged from 0.9139 to 0.9713, and the genetic distance ranged from 0.0291 to 0.0900. A phylogenetic tree was constructed using the unweighted pair group method with arithmetic mean, based on the genetic distance. The DL and YT populations originated from one clade, while the QD, LY, and ZS populations originated from another. The results indicate that the O. minor stock consisted of two genetic populations with an overall significantly analogous FST value (0.1088, P < 0.05). Most of the variance was within populations. These findings will be important for more sustainable octopus fisheries, so that this marine resource can be conserved for its long-term utilization.

Comparison of high-intensity focused ultrasound therapy under nasal endoscopy guidance versus first-line drug treatment in patients with persistent allergic rhinitis.

The aim of this study was to determine whether high-intensity focused ultrasound (HIFU) therapy under nasal endoscopy guidance could provide better efficacy and safety in patients with persistent allergic rhinitis (PAR) than the first-line drugs recommended by the World Health Organization. A total of 120 adult patients with PAR were randomly divided into 2 groups (N = 60 each). One group underwent HIFU therapy under nasal endoscopy guidance using an ultrasound rhinitis therapeutic machine. The other group served as the control group and was treated with corticosteroid nasal spray and oral cetirizine hydrochloride. All patients underwent follow-up treatment for 1 year, after which the efficacy and safety were evaluated. There was no significant difference between the two groups (P > 0.05) in the total effective rate. Moreover, no complications such as nasal adhesion, septal perforation, mucosal atrophy, and hyposmia were observed, indicating that HIFU was as effective as the first-line drug treatments recommended by the World Health Organization for symptom relief in PAR patients. The treatment efficacy, repeatability, safety, economical aspects, ease of performance, and few complications of HIFU therapy strongly suggest that HIFU should be routinely incorporated into clinical practice.

[Surveillance of soil-borne nematodiasis in Yancheng City from 2016 to 2020].

OBJECTIVE: To understand the prevalence of soil-transmitted nematode infections in Yancheng City from 2016 to 2020, so as to provide insights into the development of the scheme for further soil-transmitted nematodiasis surveillance. METHODS: Soil-borne nematode infections were detected using the modified Kato-Katz method (two slides for one sample) among the permanent residents living in Yancheng City from 2016 to 2020, and Enterobius vermicularis infection was additionally detected among children at ages of 12 years and lower using the adhesive cellophane-tape perianal swab method. The prevalence and intensity of human soil-borne nematode and E. vermicularis infections were descriptively analyzed. RESULTS: A total of 51 259 person-time residents were detected for soil-borne nematode infections in Yancheng City from 2016 to 2020, and 48 egg-positives were identified, with a 0.09% prevalence. The soil-borne nematodes infecting residents included Ascaris lumbricoides, hookworm and Trichuris trichiura, with 0.04%, 0.05% and 0.002% prevalence rates of infections, and all infections were mild. There was a region-specific prevalence of soil-borne nematode infections in Yancheng City (χ2 = 18.21, P = 0.02), with the highest prevalence seen in Funing County (0.21%), while no infections were detected in Dafeng District for five successive years. The overall prevalence of E. vermicularis infections was 0.22% among children at ages of 12 years and lower in Yancheng City. CONCLUSIONS: The prevalence of soil-borne nematode infections appears a gradual decline in residents living in Yancheng City from 2016 to 2020, and is at an extremely low level. Further surveillance of soil-transmitted nematodiasis requires to be intensified targeting key regions and populations to consolidate the control achievements.

[Investigation of Anisakis infections in market-available marine fish in Dongtai City].

OBJECTIVE: To understand the situation of Anisakis infection of in market-available marine fish in Dongtai City, so as to provide the evidence for the assessment of the risk of human Anisakis infections. METHODS: Raw and fresh marine fish caught in the sea of Dongtai City for sale were collected in 2018. The fish were weighted and dissected for the identification of Anisakis, and the prevalence and intensity of Anisakis infections were calculated. In addition, the correlation between the weight of Anisakis-infected marine fish and the infection intensity of Anisakis was examined. RESULTS: There were four species of marine fish infected with Anisakis, including Trichiurus haumela, Scomberomorus niphonius, Pneumatophorus japonicus and Larimichthys polyactis. Among the 149 fish samples, there were 78 with Anisakis infections, with a prevalence rate of 52.35%. The prevalence of Anisakis infection was 100.00% (28/28), 30.00% (9/30), 0 (0/30), 53.33% (16/30) and 80.65% (25/31) in T. haumela, S. niphonius, cuttle fish, P. japonicus and L. polyactis, respectively. A total of 1 049 Anisakis worms were collected, and the overall intensity of infection was 13.45 worms per fish. Spearman correlation analysis showed a positive correlation between the weight of T. haumela and the intensity of Anisakis infection (rs = 0.38, P = 0.047), and no correlation was found in other fish species. CONCLUSIONS: There is a high rate of Anisakis infection in marine fish along the offshore areas of Dongtai City. Intensification of health education is required and healthy and safe dietary habits are encouranged.

MiR-146a-5p inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma cells by regulating NF-κB signaling pathway.

OBJECTIVE: The aim of this study was to investigate the function and potential mechanism of micro ribonucleic acid (miR)-146a-5p in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The expression of miR-146a-5p in OSCC tissues and cell lines was examined by quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis. Then, the role of miR-146a-5p in proliferation was analyzed by Cell Counting Kit-8 (CCK-8) assay. Besides, the proliferation and apoptosis of OSCC cells were detected by the colony formation assay and flow cytometry, respectively. Finally, the regulatory effect of miR-146a-5p/nuclear factor-kappa B subunit 1 (NF-κB1) was determined by Western blotting assay and Luciferase reporter assay system. RESULTS: The expression of miR-146a-5p was markedly upregulated in OSCC cell lines. In addition, the silence of miR-146a-5p inhibited the proliferation and promoted the apoptosis of OSCC cells. According to the results of the Western blotting analysis and Luciferase reporter gene assay, NF-κB1 was identified as a direct target of miR-146a-5p. Moreover, the downregulation of NF-κB1 restored the inhibitory effect of silenced miR-146a-5p on the proliferation of SCC-9 cells. CONCLUSIONS: MiR-146a-5p can inhibit the proliferation and accelerate the apoptosis of OSCC cells by directly targeting NF-κB1, and it plays a carcinogenic role in OSCC.

[Investigation on the risk of of Anisakis infection among high - risk populations along the coastal areas of Jiangsu Province].

OBJECTIVE: To investigate the risk of Anisakis infections among high-risk populations along the coastal areas of Jiangsu Province, so as to develop the strategy for the prevention and control of anisakiasis in the province. METHODS: Three counties along the coastal areas of Jiangsu Province were selected as the study sites in 2018, including Rudong County in Nantong City, Haizhou District in Lianyungang City and Dongtai City in Yancheng City. The knowledge, attitude and practice (KAP) of anisakiasis prevention and control, and the prevalence of serum specific IgG antibody against Anisakis were investigated among high-risk populations among these three study sites, including fishermen, fish seller and people who liked eating fresh and live marine fish. Factors affecting the prevalence of the specific IgG antibody against Anisakis were identified using a multiple logistic regression model. In addition, Anisakis larvae infections were detected in fresh and live marine fish samples collected from local markets, and the prevalence and intensity of Anisakis infections were estimated. RESULTS: A total of 625 high-risk populations were investigated, including 349 men (55.8%). Only 13.0% of the subjects heard about anisakiasis, and a low awareness rate of anisakiasis prevention and control knowledge was seen among these three types of high-risk populations. There were 21.6% of the subjects eating raw or half-cooked marine fish, 5.8% eating undercooked marine fish, 3.2% presenting vomiting, nausea and diarrhea after eating marine fish, 5.1% developing systemic allergic symptoms, and 65.6% using the same chopping board for raw and cooked food. The sero-prevalence of the anti-Anisakis IgG antibody was 7.0% among the study subjects. Multiple logistic regression analysis identified education level [OR = 0.687, 95% CI (0.478, 0.987)] and development of systemic allergic symptoms [OR = 4.641, 95% CI(1.411, 15.268)]as factors affecting the positive anti-Anisakis IgG antibody among the study subjects. Among 494 fresh and live marine fish detected, the prevalence and intensity of Anisakis larvae infection was 64.0% and 8.1 larvae per fish, with high prevalence seen in Trichiurus haumela and Pneumatophorus japonicas. CONCLUSIONS: The awareness of anisakiasis prevention and control knowledge is low among the high-risk populations living along the coastal areas of Jiangsu Province, and there are high-risk behaviors, such as eating raw or half-cooked food, using the same chopping board for raw and cooked food. In addition, the prevalence of Anisakis infections is high in the marine fish in these areas. Therefore, the health education and health promotion for anisakiasis prevention and control should be intensified.

Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action.

To assess the role of exocytotic release in signaling by monoamines, we have disrupted the neuronal vesicular monoamine transporter 2 (VMAT2) gene. VMAT2-/- mice move little, feed poorly, and die within a few days after birth. Monoamine cell groups and their projections are indistinguishable from those of wild-type littermates, but the brains of mutant mice show a drastic reduction in monoamines. Using midbrain cultures from the mutant animals, amphetamine but not depolarization induces dopamine release. In vivo, amphetamine increases movement, promotes feeding, and prolongs the survival of VMAT2-/- animals, indicating that precise, temporally regulated exocytotic release of monoamine is not required for certain complex behaviors. In addition, the brains of VMAT2 heterozygotes contain substantially lower monoamine levels than those of wild-type littermates, and depolarization induces less dopamine release from heterozygous than from wild-type cultures, suggesting that VMAT2 expression regulates monoamine storage and release.

[Analysis of curative effect of transoral radiofrequency ablation microsurgery on glottic carcinoma with anterior commissure involvement at the early stage].

Objective: To explore the key technique and outcome of transoral radiofrequency ablation microsurgery for early stage of glottic carcinoma with anterior commissure involvement (ACI). Methods: A retrospective analysis was conducted on 31 patients, who were diagnosed as early stage glottic carcinoma during January 2010 to March 2016 in ENT Department. According to whether the anterior commissure was involved or not, two groups were divided. There were eleven cases with ACI (stages T1a, T1b, and T2). Twenty cases without ACI (stages Tis, T1a, and T2). All the patients received transoral radiofrequency ablation microsurgery and followed up closely.Only one case received radiotheraphy after surgery. SPSS19.0 software was used to analyze data. Results: The follow-up time was 12-67 months, and the median follow-up time was 30 months. Nine among 11 cases with ACI obtained good oncologic outcomes, initial local recurrence was identified in 2/11 cases, including 2 cases of T2. Two cases ultimately required salvage total laryngectomy. Meanwhile, initial local recurrence was identified in 2/20 cases without ACI, including 1 case of T1a and 1 case of T2. One case underwent elective neck dissection, and another one received salvage total laryngectomy.Compared to the patients without ACI, it seemed that the cases with ACI always accomponied with a little higher initial local recurrence and lower overall laryngealpreservation, but the difference had no significance (P>0.05). Conclusions: Transoral radiofrequency ablation microsurgery is an effective treatment for glottic carcinoma with ACI. Its advantages, such as more flexibility and deformability, make it more feasible to operate at the narrow space of anterior commissure assisted with laryngeal endoscopy.Good oncologic outcomes can be obtained by this technique with lower initial local recurrence as well as higher overall laryngeal preservation rate.

[Expressions and prognostic significance of PTEN and PD-1 protein in patients with classical Hodgkin's lymphoma].

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin's lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions: This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

Exogenous biliverdin ameliorates ischemia-reperfusion injury in small-for-size rat liver grafts.

OBJECTIVE: This study sought to investigate the protective potential of exogenous biliverdin (BV) for small-for-size rat liver transplants. METHODS AND RESULTS: We employed a rat orthotopic liver transplantation model using small-for-size grafts. BV (50 mumol/kg, intravenously) given to the recipient immediately before reperfusion increased 7-day survival rates (90% vs 40% in controls) and significantly diminished hepatocyte injury, as compared with a control group. These effects correlated with improved liver function and preserved hepatic architecture. BV adjuvant increased antioxidant ability, suppressed proinflammatory tumor necrosis factor-alpha expression, down-regulated proapoptotic molecules (cytochrome C and caspase-3), and inhibited most apoptotic cells. After reperfusion, there was a significant increase of c-Jun NH(2)-terminal kinase (JNK) activation and AP-1 binding ability. BV treatment effectively repressed JNK/AP-1 activation, indicating that a beneficial effect of BV treatment may be related to suppression of the JNK/AP-1 pathway. CONCLUSIONS: BV treatment alleviated ischemia-reperfusion injury at least in part via inhibition of the proinflammatory and proapoptotic JNK/AP-1 pathway. Our findings provide a rationale for a novel therapeutic approach using BV to maximize the availability of small-for-size liver grafts.

[Complications analysis of adenoidectomy and tonsillectomy assisted with ablation on children].

Objective:To analyze the complications of adenotonsilectomy assisted with coblation in children. Method:Complications of 2 089 cases of children with adenoid and tonsil surgery assisted with coblation, in our hospital nearly 10 years, were analyzed by epidemiological methods through the method of retrospective analysis. Result:①the sex ratio of male to female was 2.08：1, average age (5.87±3.12) years old, and most of 2 089 cases 76.35% (1 595/2 089) were 3-7 years old; ②all cases underwent adenoidectomy. Different surgery methods of tonsil consisted of three groups as partial resection associated with ablation was 69.17% (1 445/2 089), ablation (channeling) alone was 22.26% (465/2 089) and total resection was 8.57% (179/208). The amount of bleeding in operation was (8.52±3.18)ml, average operation time was (30.15±8.26) minutes, the postoperative pain score was (3.77±1.61); ③The incidence of postoperative complications: postoperative bleeding (all were secondary bleeding cases) rate was 0.24% (5/2 089), recurrence rate was 0.14% (3/2 089), prevertebral lymphadenitis was 0.96% (20/2 089), the other was 0.29% (torus hyperplasia in 2 cases, dyspnea in 2 cases, 1 cases of angle of mouth burned, nasopharyngeal adhesion in 1 cases). Postoperative fever rate was 9.81% (205/2 089). Conclusion:coblation technique is a good method for the treatment of children's adenoids and tonsil diseases with high efficiency and low complications. But improving the operation procedure proficiency level and skills of operation is an important link to reduce complications.

[Clinical effect analysis of adenoidectomy and tonsillectomy assisted with ablation on children].

Objective:This study aims to explore the clinical effect of adenoidectomy and tonsillectomy assisted with ablation on children.Method:The investigation took the form of retrospective review of 2 089 cases of children applied with adenoidectomy and tonsillectomy assisted with ablation in our hospital in recent 10 years. We obtained data of these children with epidemiological methods based on analyzing the status of general information and operation selections, and then analyzing the scores of snoring and breath preoperation and postoperation.Result:①General information of 2 089 cases followed with: the ratio of male and female was 2.08∶1，the average onset age was（5.87±3.12）years old, mostly ranged from 3 to 7 years old, which consists of 76.35%（1595/2089）of the group.②Different surgery methods of tonsil consisted of three groups as: partial resection associate with ablation was 69.17%(1445/2089), ablation alone was 22.26%(465/2089) and partial resection alone was 8.57%(179/2089) of the group.③A high level scores of snoring and breath more frequently found in preoperative cases than in postoperative cases(P <0.01).There are no differentiation among the scores of above three groups(P >0.05).The postoperative effect evaluation were related to allergic rhinitis, recurrent of tonsillitis, obesity, circular occipital hyperplasia and nasopharyngeal adhesion.Conclusion:The results suggested that surgery assisted with ablation has its advantage in adenoidectomy and tonsillectomy. Individual therapy for different children will improve the curative effect and relieve the pain of operation, thus is worth a wide application.