Post-operative vestibular and equilibrium evaluation in patients with cholesteatoma-induced labyrinthine fistulas.

OBJECTIVE: This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods. METHODS: Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion. RESULTS: Patients underwent fistula repair (n = 8), canal occlusion (n = 18) or obliteration procedures (n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises. CONCLUSION: Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.

[IL-8 Links NF-κB and Wnt/ß-Catenin Pathways in Persistent Inflammatory Response Induced by Chronic Helicobacter pylori Infection].

Helicobacter pylori (H. pylori) infection can cause persistent inflammatory response in human gastric mucosal epithelial cells, which may result in the occurrence of cancer. However, the underlying mechanism of carcinogenesis has not been elucidated yet. Herein, we established the models of chronic H. pylori infection in GES-1 cells and C57BL/6J mice. Interleukin 8 (IL-8) level was detected by ELISA. The expression of NF-κB p65, IL-8, Wnt2 and ß-catenin mRNA and proteins was evaluated by real-time PCR, Western blotting, immunofluorescence staining, and immunohistochemistry. The infection of H. pylori in mice was evaluated by rapid urease test, H&E staining and Warthin-Starry silver staining. The morphological changes of gastric mucosa were observed by electron microscopy. Our results showed that in H. pylori infected gastric mucosal cells along with activation of NF-κB signaling pathway and increase of IL-8 level, the expression of Wnt2 was also increased significantly, which preliminarily indicates that IL-8 can positively regulate the expression of Wnt2. Studies in chronic H. pylori infected C57BL/6J mice models showed that there was an increased incidence of premalignant lesions in the gastric mucosa tissue. Through comparing changes of gastric mucosal cell ultrastructure and analyzing the relationship between NF-κB signaling pathway and Wnt2 expression, we found that H. pylori infection activated NF-κB signal pathways, and the massive release of IL-8 was positively correlated with the high expression of Wnt2 protein. Subsequently, the activated Wnt/ß-catenin signal pathways may be involved in the malignant transformation of gastric mucosal cells. Collectively, H. pylori chronic infection may continuously lead to persistent inflammatory response: activate NF-κB pathway, promote IL-8 release and thereby activate Wnt/ß-catenin pathway. IL-8 probably plays an important role of a linker in coupling these two signal pathways.

[Clinical value of nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy].

Objective: To investigate the clinical value and efficacy of the nomogram model in evaluating the prognosis of cholangiocarcinoma after interventional therapy. Methods: The clinical data of 259 patients with cholangiocarcinoma who received interventional therapy at the First Affiliated Hospital of zhengzhou University from January 2014 to June 2021 were retrospectively analyzed, including 148 males and 111 females, aged from 26 to 91 (65±12) years. They were randomly divided into a training group (181 cases) and a validation group (78 cases) in a ratio of 7∶3. Cox regression analysis was performed in the training group, independent risk factors affecting the prognosis of patients were screened, and a nomogram for 6-month, 1-year, and 2-year survival was constructed. The performance of the nomogram was analyzed by calculating the area under the receiver operating characteristic curve (AUC) value, calibration curve, and decision curve, and the predictive efficacy of the model was evaluated in the validation group. Results: There was no significant difference in baseline data between the training group and the validation group, which was comparable. Regression analysis showed that T stage (T2: HR=0.147,95%CI: 0.077-0.281;T3: HR=0.207,95%CI: 0.122-0.351;T4: HR=0.864,95%CI: 0.537-1.393), tumor diameter (17-33 mm: HR=0.201,95%CI: 0.119-0.341;≥33 mm: HR=0.795,95%CI: 0.521-1.211) and differentiation degree(middle differentiation: HR=3.318,95%CI: 2.082-5.289;highly differentiation: HR=1.842,95%CI: 1.184-2.867) were risk factors affecting the prognosis of interventional therapy for cholangiocarcinoma. The AUC values of the survival curve prediction models were generally consistent between the training and validation groups, and the AUC values of the training group at 6 months, 1 year, and 2 years were 0.925 (95%CI: 0.888-0.963), 0.921 (95%CI: 0.877-0.964) and 0.974 (95%CI: 0.957-0.993), respectively. In the validation group, the 6-month, 1-year, and 2-year AUC values were 0.951 (95%CI: 0.911-0.991), 0.917 (95%CI: 0.857-0.977) and 0.848 (95%CI: 0.737-0.959), respectively, and the AUC values were all greater than 0.8, suggesting that the nomogram had better discrimination ability. The calibration curves of the prediction models of the two groups were basically consistent, and the shape of the calibration curves at 6 months and 1 year fitted the ideal curve, while the fitting degree of the calibration curves at 2 years was relatively poor. The decision curve showed the high clinical utility of this nomogram in predicting the 6-month, 1-year survival of patients with cholangiocarcinoma. Conclusions: T stage, tumor diameter, and differentiation are independent risk factors affecting the prognosis of patients with interventional cholangiocarcinoma, and the nomogram model proposed in this study has good distinguishing ability and exact clinical value for prognosis evaluation.

[Study on protective effects and mechanisms of total glucosides of Paeony on Graves disease in BALB/c mice].

Objective: To investigate the protective effect and its immunoregulatory mechanism of Total Glucosides of Paeony (TGP) against Graves' Disease (GD) model on BALB/c mice. Methods: Fifty female (6 weeks old, weighing 16-18 g) BALB/c mice of specific pathogen free were divided into control group according to random number table method, model group, early low-dose TGP intervention group (250 mg·kg-1·d-1), early high-dose TGP intervention group (500 mg·kg-1·d-1), and late TGP intervention group, with 10 mice in each group. Except the control group, the other 4 groups were immunized 3 times (0, 3rd, and 6th week) with recombinant adenovirus expressing the thyroid stimulating hormone receptor (TSHR) A subunit to establish the GD model. The early low-dose and high-dose intervention group were given diets containing different doses of TGP throughout the whole process, and the late intervention group was given diets containing low doses of TGP from the 1st week after the 2nd immunization (week 4). The levels of thyrotropin receptor antibody (TRAb) and total thyroxine (TT4) were detected in the tail venous blood of mice at the 4th week. At the 10th week, the serum TRAb and TT4 levels and the ratio of regulatory T cells (Treg) in each group were detected, and the pathological changes of thyroid tissue were observed. Serum helper T cell 1(Th1) and Th2 cell-related factors interleukin-2 (IL-2), IL-4, IL-5, IL-10, IL-12p70, granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon-γ (IFN-γ) and tumor necrosis factors-α (TNF-α) were detected to investigate the protective effect of TGP on GD model in BALB/c mice and its mechanism. Results: At the 4th week, The level of TT4 [(55.07±12.89) µg/L] in early high-dose intervention group was lower than that in model group [(74.33±8.63) µg/L] (all P<0.05). The level of TT4 in early low-dose intervention group and late intervention group and model group had no statistical significance (all P>0.05). TRAb level of mice between early low-dose, early high-dose, late intervention groups and model group was no significant difference (all P>0.05). At the 10th week, TRAb [(90.00±26.89) U/L] and TT4[(32.66±8.11) µg/L] levels in the early high-dose intervention group were lower than those in the model group [(396.97±95.35) U/L, (73.70±16.33) µg/L] (all P<0.05). The TRAb and TT4 levels in the early low-dose intervention group and late intervention group were not significantly different from those in the model group (all P>0.05). The thyroid tissue of hyperthyroidism mice in the early high dose intervention group showed focal hypertrophic changes, while the thyroid tissue of other hyperthyroidism mice showed diffuse hypertrophic changes. The CD4+CD25+/CD4+Treg ratio in early high-dose intervention group was higher than that in model group at the 10th week (4 weeks after three recombinant adenovirus immunization) (P<0.05). Compared with the model group at the 10th week, the levels of IL-2, IL-12p70 and IFN-γ in the early high-dose intervention group were all decreased (all P<0.05), and the levels of IL-10 were increased (P<0.05). Conclusion: Early high-dose (500 mg·kg-1·d-1) TGP intervention group displays a protective effect against GD mice, the mechanism of which may be related to regulatory T cell function changes and Th1/Th2 cytokine balance restoration.

[Multiple pulmonary masses with diffuse cystic lesions].

A 50-year-old female patient, presenting with a past history of Reynaud's syndrome, xerostomia and xerophthalmia, was admitted to Fujian Provincial Hospital because of coughing for 10 days and left anterior chest pain for 1 day. Chest imaging showed multiple nodules and masses, and diffuse cystic lesions in both lungs. Based on the differential diagnosis of multiple pulmonary masses and diffuse cystic lesions respectively, autoantibodies, radionuclide dynamic imaging of the parotid, positron emission tomography-CT, CT-guided percutaneous transthoracic needle biopsy, and other examinations were performed. The diagnosis of diffuse large B-cell lymphoma stage ⅣA (lung, parotid gland) and Sjögren's syndrome was confirmed. By analyzing the imaging features and pathogenesis in detail, the diffuse cystic lesions of both lungs were considered to be related to lymphocytic interstitial pneumonia caused by Sjögren's syndrome. The pulmonary space-occupying lesions in the lungs were significantly absorbed after RCHOP regimen for lymphoma.

[Preliminary analysis of the promotion effect of laparoscopic standardized surgical treatment for gastric cancer in regional medical centers in Shanghai].

Objective: To explore the promotion effect of laparoscopic standardized surgery for gastric cancer observational in some regional medical centers in Shanghai. Methods: A retrospective cohort study was carried out. Eleven regional medical centers in Shanghai received the promotion program of laparoscopic standardized surgery for gastric cancer, which was led by Ruijin Hospital, Shanghai Jiaotong University School of Medicine (Shanghai Minimally Invasive Surgery Center) from January to December 2020. Clinicopathological data of gastric cancer patients treated at these 11 regional medical centers before and after the promotion program were collected. Inclusion criteria were as follows: patients undergoing laparoscopic distal gastrectomy or total gastrectomy; gastric cancer confirmed by pathology; without distant metastasis or peritoneal metastasis. Patients who did not undergo laparoscopic D2 radical resection, or received neoadjuvant chemotherapy before surgery, or without complete clinical data were excluded. Patients undergoing laparoscopic surgery from January to December 2019 were included in the pre-promotion group (46 cases). Patients undergoing laparoscopic surgery from January to December 2021 were included in the post-promotion group (102 cases). In addition, patients undergoing laparoscopic surgery at Ruijin Hospital from January 2021 to December were included in the control group (138 cases). The baseline data, perioperative measurements postoperative complications, and pathological results of the three groups were analyzed and compared. Results: There were no significant differences in baseline characteristics among the three groups (all P>0.05). Compared with the pre-promotion group, the operation time in post-promotion group was significantly shorter [(207.3±36.0) minutes vs. (254.2±47.1) minutes, t=7.038,P<0.001], and the number of harvested lymph node was significantly more (24.4±12.2 vs. 18.9±5.5, t=2.900, P=0.004). However, there were no significant differences in the extent of resection, time to fluid intake, and postoperative hospital stay between the two groups (all P>0.05). Compared with the control group, the operation time [(207.3±36.0) minutes vs (172.6±26.0) minutes, t=8.281, P<0.001], time to fluid intake [(6.3±3.2) days than (5.5±3.0) days, t=2.029, P=0.044], and the postoperative hospital stay [(14.3±5.6) days vs. (10.1±4.8) days, t=6.036, P<0.001] in the post- promotion group were still longer. Total gastrectomy was less common in the post-promotion group compared with the control group [18 cases (17.6%) vs. 41 cases (29.7%), χ2=7.380, P=0.007]. However, there was no significant difference in the number of harvested lymph node between the two groups (P>0.05). The morbidity of postoperative complication in the post-promotion group (9.8%, 10/102) was significantly lower than that in the pre-promotion group (23.9%, 11/46) (χ2=5.183, P=0.023), while above morbidity was not significantly different between the post-promotion group and the control group [9.8% vs. 6.5% (9/138), χ2=0.867, P=0.352]. Conclusion: After the promotion of laparoscopic standardized surgery for gastric cancer in regional medical centers, the standardization degree of surgery has been improved, and the morbidity of postoperative complication decreases. Laparoscopic standardized surgery for gastric cancer can be promoted to more regional medical centers.

[Clinicopathological features of low-grade oncocytic renal tumor (CD117-negative, cytokeratin 7-positive): report of seven cases].

Objective: To explore clinicopathological features of low-grade oncocytic tumor (LOT) of the kidney and to analyze its relationship to hybrid oncocytic/chromophobe tumor (HOCT) of the kidney, renal oncocytoma (RO), and chromophobe renal cell carcinoma (chRCC). Methods: Seven LOTs were identified from the pathologic archives of two hospitals, including Xiangya Hospital (5 cases) and the Second Xiangya Hospital (2 cases) of Central South University between 2012 and 2019. Clinical data of the LOTs were collected. The tumor morphology was analyzed and immunohistochemistry was performed. Results: All LOTs occurred in adults, aged from 49 to 72 years (median 56.0 years, mean 60.7 years). The tumor size ranged from 2.5 to 6.0 cm (median 4.3 cm, mean 4.3 cm). There were three male and four female patients. Three cases occurred in the left kidney and four in the right. All the tumors were solitary lesions without the clinicopathologic background of Birt-Hogg-Dubé (BHD) syndrome or oncocytosis. Five patients had available follow-up data (follow-up period 23-95 months, median 69.0 months, mean 64.6 months) and all were alive without disease. Microscopically, all LOTs were well-circumscribed (7/7). Three LOTs were partly encapsulated. The tumors demonstrated a predominant growth pattern comprising prominently compact small nests surrounded by delicately branching thin-walled blood vessels, imparting an organoid architecture (7/7), but variable numbers of glandular or gland-like structures were often seen among the small nests (7/7). There were frequently areas with loose, edematous stroma, and the tumor cells exhibited reticular, trabecular, or single cell arrangements (6/7). Focal hemorrhage was also commonly present in both compact and loose areas (5/7). In addition, focally cystic formation and ossification occurred in the compact area of one case and in the loose area of another case. The tumor cells in LOT showed intermediate cytologic characteristics between RO and chRCC, including abundantly eosinophilic granular cytoplasm, ovoid to round nuclei with mostly smooth contours, discernable small nucleoli (RO features), frequently delicate perinuclear halos, and occasional binucleation (chRCC features). The tumors were typically CK7-positive and CD117-negative (7/7), and variable staining for PAX8 (5/7), P504s (2/7), and vimentin (1/7). They were negative for CK20, CD10 and FOXI1. All tumors retained SDHB immunostaining. Conclusions: LOT is a rare and indolent oncocytic renal tumor with homogeneously intermediate cytologic features between RO and chRCC. There are some clinicopathologic overlaps between LOT and sporadic HOCT. The distinctive morphology and immunophenotype of LOT suggest that it is potentially a distinct tumor entity.

LINC00839 Promotes the Progression of Gastric Cancer by Sponging miR-1236-3p.

In this paper, LINC00839 expression in gastric cancer (GC) was confirmed by real-time quantitative PCR. The function of LINC00839 in GC was detected by loss of function assays. Luciferase assays was performed to confirm the interaction between LINC00839 and miR-1236-3p. Then we investigated the regulatory effect of LINC00839 on miR-1236-3p. The results confirmed that the expression level of LINC00839 in GC was significantly up-regulated. LINC00839 could promote GC cell proliferation, mobility, and invasion. The detection of luciferase reporter gene confirmed that LINC000839 could bind to the binding site of miR-1236-3p. Our findings suggest that LINC00839 promotes GC progression through sponging miR-1236-3p.

Attenuated cell-cycle division protein 2 and elevated mitotic roles of polo-like kinase 1 characterize deficient myoblast fusion in peripheral arterial disease.

INTRODUCTION: We propose that MuSC-derived myoblasts in PAD have transcriptomic differences that can highlight underlying causes of ischemia-induced myopathy. METHODS: Differentiation capacity among perfused and ischemic human myoblasts was compared. Following next generation sequencing of mRNA, Ingenuity Pathway Analysis (IPA) was performed for canonical pathway enrichment. Live cell imaging and immunofluorescence were performed to determine myocyte fusion index and protein expression based on insights from IPA, specifically concerning cell cycle regulators including cell-division cycle protein 2 (CDC2) and polo-like kinase 1 (PLK1). RESULTS: Ischemic myoblasts formed attenuated myotubes indicative of reduced fusion. Additionally, myoblasts from ischemic segments showed significant differences in canonical pathways associated with PLK1 (upregulated) and G2/M DNA damage checkpoint regulation (downregulated). PLK1 inhibition with BI2536 did not affect cell viability in any group over 24 h but deterred fusion more significantly in PAD myoblasts. Furthermore, PLK1 inhibition reduced the expression of checkpoint protein CDC2 in perfused but not ischemic cells. CONCLUSION: Differentiating myoblasts derived from ischemic muscle have significant differences in gene expression including those essential to DNA-damage checkpoint regulation and cell cycle progress. DNA-damage checkpoint dysregulation may contribute to myopathy in PAD.

Metabolomics Changes of Serum and Tissues in Mice Died of Acute Tetracaine Poisoning.

ABSTRACT: Objective To study the changes of metabolites in serum and tissues （kidney, liver and heart） of mice died of acute tetracaine poisoning by metabolomics, to search for potential biomarkers and related metabolic pathways, and to provide new ideas for the identification of cause of death and research on toxicological mechanism of acute tetracaine poisoning. Methods Forty ICR mice were randomly divided into control group and acute tetracaine poisoning death group. The model of death from acute poisoning was established by intraperitoneal injection of tetracaine, and the metabolic profile of serum and tissues of mice was obtained by ultra-high performance liquid chromatography-electrostatic field orbitrap high resolution mass spectrometry （UPLC-Orbitrap HRMS）. Multivariate statistical principal component analysis （PCA） and orthogonal partial least square-discriminant analysis （OPLS-DA） were used, combined with t-test and fold change to identify the differential metabolites associated with death from acute tetracaine poisoning. Results Compared with the control group, the metabolic profiles of serum and tissues in the mice from acute tetracaine poisoning death group were significantly different. Eleven differential metabolites were identified in serum, including xanthine, spermine, 3-hydroxybutylamine, etc.; twenty-five differential metabolites were identified in liver, including adenylate, adenosine, citric acid, etc.; twelve differential metabolites were identified in heart, including hypoxanthine, guanine, guanosine, etc; four differential metabolites were identified in kidney, including taurochenodeoxycholic acid, 11, 12-epoxyeicosatrienoic acid, dimethylethanolamine and indole. Acute tetracaine poisoning mainly affected purine metabolism, tricarboxylic acid cycle, as well as metabolism of alanine, aspartic acid and glutamic acid. Conclusion The differential metabolites in serum and tissues of mice died of acute tetracaine poisoning are expected to be candidate biomarkers for this cause of death. The results can provide research basis for the mechanism and identification of acute tetracaine poisoning.

[Clinical diagnosis and treatment of 27 cases of metanephric adenoma].

The clinical features, imaging features, treatment methods and pathological features of 27 patients with metanephric adenoma were analyzed. It was found that the clinical features and imaging features of metanephric adenoma were difficult to differentiate from renal malignantology. Pathology can be clearly diagnosed and some can be combined with malignant components. Nephron sparing surgery is the first choice, and the prognosis is good, but still need regular follow-up.

MiR-223-3p inhibits inflammation and pyroptosis in monosodium urate-induced rats and fibroblast-like synoviocytes by targeting NLRP3.

Down-regulated miR-223-3p was found in rheumatoid arthritis. This study aimed to further explore the level and role of miR-223-3p in gout arthritis (GA). After monosodium urate (MSU)-induced GA rat and fibroblast-like synoviocytes (FLSs) models were established, the rat paw volume and gait score were documented and the FLSs were transfected with miR-223-3p mimic/inhibitor or NLR family pyrin domain containing 3 (NLRP3) over-expression plasmids. The MiR-223-3p target was found through bioinformatics and the dual-luciferase reporter. The rat joint pathological damage was observed by hematoxylin and eosin staining. The levels of interleukin (IL)-1ß, tumor necrosis factor (TNF)-α and articular elastase in rats were detected by enzyme-linked immunosorbent assay (ELISA). The viability and pyroptosis of FLSs were detected by methyl thiazolyl tetrazolium (MTT) and flow cytometry. The expressions of miR-223-3p, NLRP3, cleaved caspase-1, IL-1ß, apoptosis-associated speck-like protein (AS) and cleaved N-terminal gasdermin D (GSDMD) in FLSs or rat synovial tissues were detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Western blot or immunohistochemistry analysis. MSU increased the paw volume, gait score, inflammation in synovial tissues and increased the levels of IL-1ß, TNF-α and articular elastase in rats. MSU decreased the viability and increased the pyroptosis of FLSs, up-regulated the expression of NLRP3, ASC, cleaved caspase-1, cleaved N-terminal GSDM, and IL-1ß, and down-regulated miR-223-3p expression in synovial tissues of rat joints and FLSs. MiR-223-3p mimic reversed the effect of MSU on lowering cell viability, increasing pyroptosis in FLSs, while miR-223-3p inhibitor further enhanced the effect of MSU on FLSs. NLRP3 was a target of miR-223-3p. Also, NLRP3 over-expression reversed the effects of miR-223-3p on MSU-induced FLSs. MiR-223-3p inhibited pyroptosis in MSU-induced rats and FLSs by targeting NLRP3.

[Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer].

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

Identification of ELAVL1 gene and miRNA-139-3p involved in the aggressiveness of NSCLC.

OBJECTIVE: Tumor metastasis remains the main cause for the cancer-associated death of human non-small-cell lung carcinoma (NSCLC). Many studies have verified that microRNAs (miRNAs) exert crucial functions in the development of NSCLC. Nevertheless, the functions of miR-139-3p in NSCLC remain unexplored. PATIENTS AND METHODS: The quantitative Real Time-PCR (qRT-PCR) assay was applied to assess the level of miR-139-3p and ELAV like RNA binding protein 1 (ELAVL1) in NSCLC tissues and cell lines. The growth of NSCLC cell was analyzed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and colony formation assay. The migration ability and invasiveness of NSCLC cells were analyzed using wound healing and transwell invasion analysis. The expression of ELAVL1 was determined by immunoblotting assay. The growth of NSCLC cell in vivo was assessed using xenograft model. RESULTS: We uncovered that miR-139-3p was down expressed in NSCLC. MiR-139-3p repressed NSCLC cell growth, migration as well as invasion in vitro, and suppressed the progression of NSCLC cell in vivo. Mechanistically, ELAVL1 was proved as a downstream target of miR-139-3p. The level of ELAVL1 was upregulated in NSCLC and inversely associated with miR-139-3p level. Immunoblotting assay suggested that ELAVL1 was negatively modulated by miR-139-3p in NSCLC cell. In vivo, miR-139-3p repressed NSCLC cell growth and metastasis. Several recuse assays revealed that ELAVL1 mediated the inhibitory actions of miR-139-3p on the growth and metastatic-related traits of NSCLC cell. CONCLUSIONS: Our results indicate that miR-139-3p acts as a suppressor in modulating the aggressiveness of NSCLC via regulating ELAVL1.

[Influence of different anastomotic methods on gastric function].

Segmental gastrectomy is a common function preserving operation, and its combination with sentinel lymph node navigation technology shows a broad prospect in the treatment of early gastric cancer. Commonly anastomosis methods include the follows: (1) Hand-sewn anastomosis: this method is relatively simple, reduces the use of stapler, and can effectively reduce surgical cost. However, laparotomy or small-incision assisted laparoscopic surgery is required to accomplish anastomosis, so the surgical wound is relatively large. (2) Delta anastomosis: this anastomosis is entirely endoscopic, requiring no small incision with less surgical trauma. However, due to the presence of residual cavities in the small curvature of the side-to-side anastomosis, and the possibility of excessive incision of the posterior wall of the stomach, which may shorten the pyloric sleeve, there is an increased risk of gastric stasis after the operation. (3) Hybrid technique: this anastomosis method is safe and effective. However, it requires total endoscopic gastric anterior wall suture, which represents higher requirements for surgeons. Therefore, surgeons experienced in minimally invasive surgeries are recommended to perform this anastomosis. (4) Puncture technique: this anastomotic method is end-to-end anastomosis with low risk of gastric stasis, and is applicable for entirely endoscopic anastomosis. However, the stapler is not typically used for gastrointestinal surgery, which brings certain limitations to clinical promotion. These anastomoses have their own advantages and disadvantages, and their effects on gastric function are also controversial. In conclusion, the development of segmental gastrectomy is still in its infancy, and prospective multicenter randomized controlled trials are awaited to confirm the safety of oncology and standardize the techniques.

[Laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis].

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.

MicroRNA-215-3p suppresses the growth and metastasis of cervical cancer cell via targeting SOX9.

OBJECTIVE: The aim of the current study was to investigate the potential roles of miR-215-3p in the progression of cervical cancer. PATIENTS AND METHODS: The levels of miR-215-3p in both cervical cancer tissues and cell lines were detected using quantitative Real-time polymerase chain reaction (qRT-PCR) assay. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, migration and invasion assays were applied to investigate the role of miR-215-3p on the growth and aggressiveness of cervical carcinoma SiHa cell. The expression of SRY-Box 9 (SOX9) was assessed by Western blotting assay. The Xenograft model and lung metastasis model were applied to reveal the impact of miR-215-3p on the growth and distant metastasis of cervical carcinoma cell in vivo. Moreover, miR-215-3p and a SOX9 siRNA were co-transfected into the SiHa cell to investigate the underlying mechanism of miR-215-3p-SOX9 on cervical cancer tumorigenesis. RESULTS: We used genome-wide gene expression analysis using clinical cervical cancer samples to identify that miR-215-3p was down-regulated in cervical cancer. We then collected 31 pairs of cervical cancer and the corresponding non-cancerous tissues to determine miR-215-3p level and indicated that miR-215-3p was significantly down-expressed in cervical cancer. Furthermore, the functional analysis suggested that over-expression of miR-215-3p suppressed the aggressiveness of SiHa cell, whereas down-regulation led to the opposite results. We identified SOX9 as a direct target of miR-215-3p, and its level was negatively related to the level of miR-215-3p in cervical carcinoma tissue. Up-regulation of SOX9 reversed the suppressive impact of miR-215-3p on cervical carcinoma cell, and down-regulation of SOX9 reversed the promote effects of miR-215-3p CONCLUSIONS: These findings showed the important role of the miR-215-3p/SOX9 axis in the progression of cervical carcinoma.

EFFECT OF DORSOMEDIAL HYPOTHALAMUS NEUROPEPTIDE Y KNOCKDOWN ON HEPATIC INSULIN SENSITIVITY.

OBJECTIVE: In this study we investigated the effect of dorsomedial hypothalamus (DMH) neuropeptide Y (NPY) knock-down on hepatic insulin sensitivity in high-fat (HF) diet-fed rats. METHODS: Forty-eight Sprague-Dawley rats were randomly assigned to receive bilateral DMH injections of adeno-associated virus AAVshNPY or AAVshCTL and then accessed to regular chow. Five weeks after viral injection, half rats in each group were given access to the HF diet. At 16 weeks, rat livers were collected. Insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) mRNA expression was measured by qRT-PCR. Blood glucose levels were measured by the oxidase method, serum insulin, triglyceride, and TC levels were measured by Elisa. Pathological changes in the liver were assessed by hematoxylin-eosin (HE) staining. AKT, p-AKT, and GSK-3 levels were measured by western blotting. RESULTS: Compared with AAVshCTL-injected rats, AAVshNPY-injected rats showed a significant decrease in blood glucose concentrations; serum insulin, triglyceride, and TC; HOMA-IR; and IRS-1 and PI3K mRNA levels (P<0.05). ISI, GSK-3, and p-AKT levels were significantly increased (P<0.05). HE staining showed that AAVshNPY-injected rats fed the HF diet had mild fatty degeneration. CONCLUSION: These results suggest that DMH NPY knock-down improves hepatic insulin sensitivity in HF diet-fed rats by activating the hepatic PI3K/AKT insulin signalling pathway.

[Basal squamous cell carcinoma of external auditory meatus: a case report].

Summary The patient developed repeated itching and scabbing at the mouth of the left external auditory canal 5 years ago. In the last two years, the tumor is enlarged. After admission, the left external auditory canal can be seen as a reddish mass, brittle and easy to bleed. CT of temporal bone showed that the soft tissue shadow of left external auricle and external auditory canal was thickened. Postoperative pathological findings: (left external auditory canal) basal cell squamous cell carcinoma. According to the history, physical examination and laboratory examination, the diagnosis is considered as basal squamous cell carcinoma of the external auditory meatus.