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This report describes a case of pulmonary epithelioid haemangioendothelioma presented as multi-organ metastases including lung, liver and bone in a 56-year-old woman with an initial diagnosis made with thoracoscopic wedge biopsy. The diagnosis is confirmed through immunohistochemistry. This is a rare disease, with approximately 90 cases described in the English literature and approximately 10 cases reported in China. The case of PEH presented as multiple pulmonary nodules and metastasing to liver and bone is rare in the English literature. The rarity of this condition, the lack of clear standards for treatment, and the partial-to-complete spontaneous regression of EHE seen in some patients up to 15 years from initial detection makes it difficult to decide on the most appropriate treatment. This report may contribute to the data on clinical findings and natural history of this rare tumor. [ABSTRACT FROM AUTHOR]

Cathelicidins are important antimicrobial peptides in various vertebrate species where they are crucial parts of the innate immune system. The current understanding of amphibian cathelicidins is limited, particularly with regard to their immunomodulatory effects. To address this knowledge gap, we produced the cDNA sequence of the cathelicidin gene from a skin transcriptome of the Chinese spiny frog Quasipaa spinosa. The amino acid sequence of the Quasipaa spinosa cathelicidin (QS-CATH) was predicted to consist of a signal peptide, a cathelin domain, and a mature peptide. Comparative analysis of the QS-CATH amino acid sequence with that of other amphibian cathelicidins revealed high variability in the functional mature peptide among amphibians, whereas the cathelin domain was conserved. The QS-CATH gene was expressed in several tissues, with the highest level of expression in the spleen. Upregulation of QS-CATH after Aeromonas hydrophila infection occurred in the kidney, gut, spleen, skin, and liver. Chemically synthesized QS-CATH exhibited pronounced antibacterial activity against Shigella flexneri, Staphylococcus warneri, Escherichia coli, Salmonella enterica, and Listeria monocytogenes. Furthermore, QS-CATH disrupted the cell membrane integrity of S. flexneri, as evidenced by a lactate dehydrogenase release assay, and it hydrolyzed the genomic DNA of S. flexneri. Additionally, QS-CATH elicited chemotaxis and modulated the expression of inflammatory cytokine genes in RAW264.7 mouse leukemic monocyte/macrophage cells. These findings confirm the antimicrobial effects of amphibian cathelicidin and its ability to influence immune cell function. This will expedite the potential utilization of amphibian antimicrobial peptides as therapeutic agents., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: To review the changes and survey on status quo of the surgical treatment for esophageal cancer in China. The differences in diagnosis and treatment for esophageal cancer among hospitals in different regions across China were also investigated., Methods: We sent questionnaires to 46 hospitals across China, investigating the volume of esophageal cancer surgeries, surgical procedures, and perioperative management under the guidance of esophageal surgery chiefs., Results: A total of 46 questionnaires were sent out and collected. The survey results showed that in the past 5 years, the volume of surgeries for esophageal cancer remained stable by 23.9% of those hospitals, increased by 30.4%, and decreased by 45.7%. Of those patients treated by surgery, 19.1% were in the early stages, and 80.9% were in locally advanced stages. In terms of surgical procedures, 73.4% of the patients were treated by minimally invasive surgery and 85.7% of esophageal substitutes were a gastric conduit, 93.1% of the substitutes were pulled to the neck through the esophageal bed. For the lymph node dissection, 78.5% of the patients had a complete two-field lymph node dissection including the para-recurrent laryngeal nerve lymph nodes. Of the patients with neoadjuvant therapy, 53.5% received chemotherapy or chemotherapy plus immunotherapy (47.0%), and 43.5% had chemoradiation., Conclusions: Currently, in China, minimally invasive surgery-oriented multimodality treatment, including complete two-field lymph node dissection, has become the standard approach for esophageal cancer management. Over the past decade, this standardized approach has significantly improved prognosis compared to previous decades., (© 2024 The Author(s). Thoracic Cancer published by John Wiley & Sons Australia, Ltd.)

The status of lymph node metastasis is an important parameter affecting the survival of patients with esophageal carcinoma, which is primarily determined by histological type and the depth of invasion. However, affected by pathological features, heterogeneity and individual differences of tumors, the present staging system of lymph node in esophageal carcinoma has not been unified, the rule of lymph node metastasis remains unclear, and the extent of lymphadenectomy is still controversial. Current lymph node staging system for esophageal carcinoma may be not effective enough, which may lead to inaccurate assessment of the stage and affect the clinicians' choice of treatment modalities, or even affect the conclusions of clinical trials. Therefore, it is essential to optimize the current lymph node staging system for esophageal carcinoma to guide the surgery-based multidisciplinary treatment, and effectively to evaluate the therapeutic effects and predict patients' prognosis.

Objective: To understand the characteristics and influencing factors of lymph node metastasis of the right recurrent laryngeal nerve in thoracic esophageal squamous cell carcinoma (ESCC), and to explore the reasonable range of lymph node dissection and the value of right recurrent laryngeal nerve lymph node dissection. Methods: The clinicopathological data with thoracic ESCC were retrospectively analyzed, and the characteristics of lymph node metastasis along the right recurrent laryngeal nerve and its influencing factors were explored. Results: Eighty out of 516 patients had lymph node metastasis along the right recurrent laryngeal nerve, the metastasis rate was 15.5%. Among 80 patients with lymph node metastasis along the right recurrent laryngeal nerve, 25 cases had isolated metastasis to the right recurrent laryngeal nerve lymph node but no other lymph nodes. The incidence of isolated metastasis to the recurrent laryngeal nerve lymph node was 4.8% (25/516). A total of 1 127 lymph nodes along the right recurrent laryngeal nerve were dissected, 115 lymph nodes had metastasis, and the degree of lymph node metastasis was 10.2%. T stage, degree of tumor differentiation and tumor location were associated with right paraglottic nerve lymph node metastasis (all P <0.05). The lymph node metastasis rate along the right recurrent laryngeal in patients with upper thoracic squamous cell carcinoma (23.4%, 26/111) was higher than that of patients with middle (13.5%, 40/296) and lower (12.8%, 14/109) thoracic squamous cell carcinoma ( P =0.033). In patients with poorly differentiated ESCC (20.6%, 37/180) the metastasis rate was higher than that of patients with moderately (14.6%, 39/267) and well-differentiated (5.8%, 4/69; P <0.05). The lymph node metastasis rate of patients with stage T4 (27.3%, 3/11) was higher than that of patients with stage T1 (9.6%, 19/198), T2 (19.0%, 16/84) and T3 (18.8%, 42/1 223; P <0.05). Multivariate regression analysis showed that tumor location ( OR =0.61, 95% CI: 0.41-0.90, P =0.013), invasion depth ( OR =1.46, 95% CI: 1.11-1.92, P =0.007), and differentiation degree ( OR =1.67, 95% CI: 1.13-2.49, P =0.011) were independent risk factors for lymph node metastasis along right recurrent laryngeal nerve of ESCC. Conclusions: The lymph node along the right recurrent laryngeal nerve has a higher rate of metastasis and should be routinely dissected in patients with ESCC. Tumor location, tumor invasion depth, and differentiation degree are risk factors for lymph node metastasis along right recurrent laryngeal nerve in patients with ESCC.

Esophageal cancer is a malignant tumor with a high incidence in China. At pesent, advanced esophageal cancer patients are still frequently encountered. The primary treatment for resectable advanced esophageal cancer is surgery-based multimodality therapy, including preoperative neoadjuvant therapy, such as chemotherapy, chemoradiotherapy or chemotherapy plus immunotherapy, followed by radical esophagectomy with thoraco-abdominal two-field or cervico-thoraco-abdominal three-field lymphadenectomy via minimally invasive approach or thoracotomy. In addition, adjuvant chemotherapy, radiotherapy, or chemoradiotherapy, or immunotherapy may also be administered if suggested by postoperative pathological results. Although the treatment outcome of esophageal cancer has improved significantly in China, many clinical issues remain controversial. In this article, we summarize the current hotspots and important issues of esophageal cancer in China, including prevention and early diagnosis, treatment selection for early esophageal cancer, surgical approach selection, lymphadenectomy method, preoperative neoadjuvant therapy, postoperative adjuvant therapy, and nutritional support treatment.

In dimorphic fungi, the yeast-to-filament transition critical for cell survival under nutrient starvation is controlled by both activators and repressors. However, very few filamentation repressors are known. Here we report that, in the dimorphic yeast Yarrowia lipolytica, the conserved transcription factor YlNrg1 plays a minor role whereas Fts1, a newly identified Zn(II) 2 Cys 6 zinc cluster transcription factor, plays a key role in filamentation repression. FTS1 deletion caused hyperfilamentation whereas Fts1 overexpression drastically reduced filamentation. The expression of FTS1 is downregulated substantially during the yeast-to-filament transition. Transcriptome sequencing revealed that Fts1 represses 401 genes, including the filamentation-activating transcription factor genes MHY1, YlAZF1, and YlWOR4 and key cell wall protein genes. Tup1-Ssn6, a general transcriptional corepressor, is involved in the repression of many cellular functions in fungi. We show that both YlTup1 and YlSsn6 strongly repress filamentation in Y. lipolytica. YlTup1 and YlSsn6 together repress 1383 genes, including a large number of transcription factor and cell wall protein genes, which overlap substantially with Fts1-repressed genes. Fts1 interacts with both YlTup1 and YlSsn6, and LexA-Fts1 fusion represses a lexAop-promoter-lacZ reporter in a Tup1-Ssn6-dependent manner. Our findings suggest that Fts1 functions as a transcriptional repressor, directing the repression of target genes through the Tup1-Ssn6 corepressor., (© 2022 John Wiley & Sons Ltd.)

The yeast-to-filament transition is an important cellular response to environmental stimulations in dimorphic fungi. In addition to activators, there are repressors in the cells to prevent filament formation, which is important to keep the cells in the yeast form when filamentation is not necessary. However, very few repressors of filamentation are known so far. Here, we identify a novel repressor of filamentation in the dimorphic yeast Yarrowia lipolytica, Fts2, which is a C 2 H 2 -type zinc finger transcription factor. We show that fts2 Δ cells exhibited increased filamentation under mild filament-inducing conditions and formed filaments under non-filament-inducing conditions. We also show that Fts2 interacts with YlSsn6, component of the Tup1-Ssn6 transcriptional corepressor, and Fts2-LexA represses a lexAop-P YlACT1 -lacZ reporter in a Tup1-Ssn6-dependent manner, suggesting that Fts2 has transcriptional repressor activity and represses gene expression via Tup1-Ssn6. In addition, we show that Fts2 represses a large number of cell wall protein genes and transcription factor genes, some of which are implicated in the filamentation response. Interestingly, about two-thirds of Fts2-repressed genes are also repressed by Tup1-Ssn6, suggesting that Fts2 may repress the bulk of its target genes via Tup1-Ssn6. Lastly, we show that Fts2 expression is downregulated in response to alkaline pH and the relief of negative control by Fts2 facilitates the induction of filamentation by alkaline pH. IMPORTANCE The repressors of filamentation are important negative regulators of the yeast-to-filament transition. However, except in Candida albicans, very few repressors of filamentation are known in dimorphic fungi. More importantly, how they repress filamentation is often not clear. In this paper, we report a novel repressor of filamentation in Y. lipolytica. Fts2 is not closely related in amino acid sequence to CaNrg1 and Rfg1, two major repressors of filamentation in C. albicans, yet it represses gene expression via the transcriptional corepressor Tup1-Ssn6, similar to CaNrg1 and Rfg1. Using transcriptome sequencing, we determined the whole set of genes regulated by Fts2 and identified the major targets of Fts2 repression, which provide clues to the mechanism by which Fts2 represses filamentation. Our results have important implications for understanding the negative control of the yeast-to-filament transition in dimorphic fungi.

Background: Left thoracic approach (LTA) has been a favorable selection in surgical treatment for esophageal cancer (EC) patients in China before minimally invasive esophagectomy (MIE) is popular. This study aimed to demonstrate whether right thoracic approach (RTA) is superior to LTA in the surgical treatment of middle and lower thoracic esophageal squamous cell carcinoma (TESCC)., Methods: Superiority clinical trial design was used for this multicenter randomized controlled two-parallel group study. Between April 2015 and December 2018, cT1b-3N0-1M0 TESCC patients from 14 centers were recruited and randomized by a central stratified block randomization program into LTA or RTA groups. All enrolled patients were followed up every three months after surgery. The software SPSS 20.0 and R 3.6.2. were used for statistical analysis. Efficacy and safety outcomes, 3-year overall survival (OS) and disease-free survival (DFS) were calculated and compared using the Kaplan-Meier method and the log-rank test., Results: A total of 861 patients without suspected upper mediastinal lymph nodes (umLN) were finally enrolled in the study after 95 ineligible patients were excluded. 833 cases (98.7%) were successfully followed up until June 1, 2020. Esophagectomies were performed via LTA in 453 cases, and via RTA in 408 cases. Compared with the LTA group, the RTA group required longer operating time (274.48±78.92 vs . 205.34±51.47 min, P<0.001); had more complications (33.8% vs. 26.3% P=0.016); harvested more lymph nodes (LNs) (23.61±10.09 vs. 21.92±10.26, P=0.015); achieved a significantly improved OS in stage IIIa patients (67.8% vs. 51.8%, P=0.022). The 3-year OS and DFS were 68.7% and 64.3% in LTA arm versus 71.3% and 63.7% in RTA arm (P=0.20; P=0.96)., Conclusions: Esophagectomies via both LTA and RTA can achieve similar outcomes in middle or lower TESCC patients without suspected umLN. RTA is superior to LTA and recommended for the surgical treatment of more advanced stage TESCC due to more complete lymphadenectomy., Trial Registration: ClinicalTrials.gov NCT02448979., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-3810/coif). YSM, SGG, YL, ALH, JFL, XFL, THR, JHF, JQM, MQX, RQZ, GMX, XNF, KNC, WMM, YYL, HXL, ZRZ, YF, DHF, XDW, LGY, SM, WQW, YBG, JH report that this work was supported by the grants from National Science and Technology Support Program (Study ID Number: NKTRDP-2015BAI12B08-01, YSM). The other authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)

Esophageal cancer is one of the most common malignant tumors of digestive tract, lymph node metastasis is a frequently encountered metastasis in the esophageal cancer patients. The number of lymph node metastasis is reported as an important prognostic factor, and it also affects the choice of postoperative treatments in the esophageal cancer. It was reported that the recurrent laryngeal nerve lymph nodes are the most common sites of nodal metastasis and need to be completely dissected during the esophagectomy for thoracic esophageal cancers. Dissection of the lymph nodes along bilateral recurrent laryngeal nerves not only improves the accuracy of staging, but also improves postoperative survival of esophageal cancer patients due to reducing the local recurrence. However, it also brings problems such as injury of laryngeal recurrent nerves, and increases postoperative complications such as pulmonary complications and malnutrition due to aspiration and coughing. Therefore, it is necessary to preserve the structure and function of bilateral recurrent laryngeal nerves during esophagectomy through careful manipulations, and minimize the impact of complications in prognosis and quality of life from injury to the recurrent laryngeal nerve.

With the wide application of high-resolution chest CT in health check-up, the ground glass nodule(GGN) has been increasingly detected. GGNs have a complex etiology and image features, which can develop fast or very slowly. Therefore, whether to follow up or to resect it is usually very difficult to be determined. Overdiagnosis or overtreatment frequently happens. According to the development of GGNs, the process can be clinically divided into four stages: biological onset stage (pre-detection stage), observational stage, clinical treatment stage and postoperative follow-up stage. This review summarizes the progress on the natural development process, imaging monitoring and differentiation, the optimal time of surgical treatment for GGNs based on the decision of multidisciplinary team. This revie wmay be helpful for clinicians to understand the rule of GGN development in the follow-up, and find an optimal time to give surgical intervention for improving the prognosis of and life quality of the GGN patients.

Insulin resistance is the main sign of type 2 diabetes mellitus and is often accompanied by the infiltration of inflammatory factors. These inflammatory factors are mainly produced and secreted by macrophages. The purpose of the current study was to explore the relationship between macrophages and insulin resistance, and to determine its underlying mechanism. The insulin resistance of macrophages was induced by palmitic acid (PA) in vitro . The glucose uptake rate of macrophages, the expression levels of inflammatory cytokines and the expression levels of insulin resistance-related proteins were detected. The protein expression levels of Krüppel-like factor 4 (KLF4), toll-like receptor 4 (TLR4), NF-κB and Galectin-3 (Gal-3) were detected via western blotting and recovery experiments were performed by combining the Gal-3 and TLR4 inhibitors GB1107 and TAK242. The results revealed that PA-induced macrophages demonstrated insulin resistance. Additionally, KLF4 protein was inhibited and the sugar uptake rate was significantly lower than that of the control group. Western blotting and immunofluorescence assays revealed that the expression of Gal-3 in PA-induced macrophages was significantly upregulated. The addition of the Gal-3 inhibitor GB1107 significantly increased glucose utilization and reduced insulin resistance in PA-treated cells. Inhibitor of TLR4 inhibited the protein expression level of the TLR4/NF-κB pathway. In conclusion, PA promoted the TLR4/phosphorylated-NF-κB signaling pathway by inhibiting KLF4, promoted the upregulation of Gal-3 expression and improved the insulin resistance of macrophages., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Li et al.)

Environmental pH influences cell growth and differentiation. In the dimorphic yeast Yarrowia lipolytica , neutral-alkaline pH strongly induces the yeast-to-filament transition. However, the regulatory mechanism that governs alkaline pH-induced filamentation has been unclear. Here, we show that the pH-responsive transcription factor Y. lipolytica Rim101 (YlRim101) is a major regulator of alkaline-induced filamentation, since the deletion of Yl RIM101 severely impaired filamentation at alkaline pH, whereas the constitutively active Yl RIM101 1-330 mutant mildly induced filamentation at acidic pH. YlRim101 controls the expression of the majority of alkaline-regulated cell wall protein genes. One of these, the cell surface glycosidase gene Yl PHR1 , plays a critical role in growth, cell wall function, and filamentation at alkaline pH. This finding suggests that YlRim101 promotes filamentation at alkaline pH via controlling the expression of these genes. We also show that, in addition to YlRim101, the Msn2/Msn4-like transcription factor Mhy1 is highly upregulated at alkaline pH and is essential for filamentation. However, unlike YlRim101, which specifically regulates alkaline-induced filamentation, Mhy1 regulates both alkaline- and glucose-induced filamentation, since the deletion of MHY1 abolished them both, whereas the overexpression of MHY1 induced strong filamentation irrespective of the pH or the presence of glucose. Finally, we show that YlRim101 and Mhy1 positively coregulate seven cell wall protein genes at alkaline pH, including Yl PHR1 and five cell surface adhesin-like genes, three of which appear to promote filamentation. Together, these results reveal a conserved role of YlRim101 and a novel role of Mhy1 in the regulation of alkaline-induced filamentation in Y. lipolytica IMPORTANCE The regulatory mechanism that governs pH-regulated filamentation is not clear in dimorphic fungi except in Candida albicans Here, we investigated the regulation of alkaline pH-induced filamentation in Yarrowia lipolytica , a dimorphic yeast distantly related to C. albicans Our results show that the transcription factor YlRim101 and the Msn2/Msn4-like transcription factor Mhy1 are the major regulators that promote filamentation at alkaline pH. They control the expression of a number of cell wall protein genes important for cell wall organization and filamentation. Our results suggest that the Rim101/PacC homologs play a conserved role in pH-regulated filamentation in dimorphic fungi., (Copyright © 2021 Shu et al.)

Background: The purpose of this study was to explore the prognostic factors of oesophageal signet ring cell (SRC) carcinoma and to construct a nomogram for predicting the outcome of SRC carcinoma of oesophagus., Methods: A total of 968 cases of oesophageal SRC carcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. Cases were divided into training cohort and validation cohort. Univariate and multivariable Cox analyses was performed to select the predictors of overall survival (OS for the nomogram. The performance of nomogram was validated with Harrell's concordance index (C-index), calibration curves and decision curve analysis (DCA)., Results: The 1- and 5-year OS in the training cohort were 0.446 and 0.146, respectively, and the 1- and 5-year OS in the validation cohort were 0.459 and 0.138. The independent prognostic factors for establishing the nomogram were marital status, invasion of the surrounding tissue, lymph node metastasis, distant metastasis, surgery and chemotherapy. The Harrell's c-index value of the training cohort and validation cohort were 0.723 and 0.708. In the calibration curves, the predicted survival probability and the actual survival probability have a considerable consistency. DCA indicated the favourable potential clinical utility of the nomogram., Conclusions: A nomogram to predict the OS of patients with oesophageal SRC carcinoma was established. The validation of the nomogram fully demonstrates its great performance., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd-20-3084). The authors have no conflicts of interest to declare., (2021 Journal of Thoracic Disease. All rights reserved.)

Background: Signet ring cell carcinoma is a rare type of oesophageal cancer, and we hypothesized that log odds of positive lymph nodes (LODDS) is a better prognostic factor for oesophageal signet ring cell carcinoma., Aim: To explore a novel prognostic factor for oesophageal signet ring cell carcinoma by comparing two lymph node-related prognostic factors, log odds of positive LODDS and N stage., Methods: A total of 259 cases of oesophageal signet ring cell carcinoma after oesopha-gectomy were obtained from the Surveillance, Epidemiology, and End Results database between 2006 and 2016. The prognostic value of LODDS and N stage for oesophageal signet ring cell carcinoma was evaluated by univariate and multivariate analyses. The Akaike information criterion and Harrell's C-index were used to assess the value of two prediction models based on lymph nodes. External validation was performed to further confirm the conclusion., Results: The 5-year cancer-specific survival (CSS) and 5-year overall survival (OS) rates of all the cases were 41.3% and 27.0%, respectively. The Kaplan-Meier method showed that LODDS had a higher score of log rank chi-squared (OS: 46.162, CSS: 41.178) than N stage (OS: 36.215, CSS: 31.583). Univariate analyses showed that insurance, race, T stage, M stage, TNM stage, radiation therapy, N stage, and LODDS were potential prognostic factors for OS ( P < 0.1). The multivariate Cox regression model showed that LODDS was an significant independent prognostic factor for oesophageal signet ring carcinoma patients after surgical resection ( P < 0.05), while N stage was not considered to be a significant prognostic factor ( P = 0.122). Model 2 (LODDS) had a higher degree of discrimination and fit than Model 1 (N stage) (LODDS vs N stage, Harell's C-index 0.673 vs 0.656, P < 0.001; Akaike information criterion 1688.824 vs 1697.519, P < 0.001). The results of external validation were consistent with those in the study cohort., Conclusion: LODDS is a superior prognostic factor to N stage for patients with oesophageal signet ring cell carcinoma after oesophagectomy., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the article., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Total pancreatectomy (TP) is usually considered a therapeutic option for pancreatic cancer in which Whipple surgery and distal pancreatectomy are undesirable, but brittle diabetes and poor quality of life (QoL) remain major concerns. A subset of patients who underwent TP even died due to severe hypoglycemia. For pancreatic cancer involving the pancreatic head and proximal body but without invasion to the pancreatic tail, we performed partial pancreatic tail preserving subtotal pancreatectomy (PPTP-SP) in selected patients, in order to improve postoperative glycemic control and QoL without compromising oncological outcomes., Aim: To evaluate the efficacy of PPTP-SP for patients with pancreatic cancer., Methods: We retrospectively reviewed 56 patients with pancreatic ductal adenocarcinoma who underwent PPTP-SP ( n = 18) or TP ( n = 38) at our institution from May 2014 to January 2019. Clinical outcomes were compared between the two groups, with an emphasis on oncological outcomes, postoperative glycemic control, and QoL. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30 and EORTC PAN26). All patients were followed until May 2019 or until death., Results: A total of 56 consecutive patients were enrolled in this study. Perioperative outcomes, recurrence-free survival, and overall survival were comparable between the two groups. No patients in the PPTP-SP group developed cancer recurrence in the pancreatic tail stump or splenic hilum, or a clinical pancreatic fistula. Patients who underwent PPTP-SP had significantly better glycemic control, based on their higher rate of insulin-independence ( P = 0.014), lower hemoglobin A1c (HbA1c) level ( P = 0.046), lower daily insulin dosage ( P < 0.001), and less frequent hypoglycemic episodes ( P < 0.001). Global health was similar in the two groups, but patients who underwent PPTP-SP had better functional status ( P = 0.036), milder symptoms ( P = 0.013), less severe diet restriction ( P = 0.011), and higher confidence regarding future life ( P = 0.035)., Conclusion: For pancreatic cancer involving the pancreatic head and proximal body, PPTP-SP achieves perioperative and oncological outcomes comparable to TP in selected patients while significantly improving long-term glycemic control and QoL., Competing Interests: Conflict-of-interest statement: We declare that we have no conflicts of interest related to this study., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Preoperative nutritional status plays an important role in predicting postoperative outcomes. Prognostic Nutritional Index (PNI) and Controlling Nutritional Status (CONUT) are good tools to assess patients' nutritional status. They have been used in predicting outcomes in various malignancies, but few studies have focused on pancreatic adenocarcinoma (PDAC) patients. Totally, 306 PDAC patients were enrolled. The propensity score matching (PSM) method was introduced to eliminate the baseline inequivalence. Patients with different PNI (or CONUT) scores showed inequivalence baseline characteristics, and patients with compromised nutritional status were related with a more advanced tumour stage. After PSM, the baseline characteristics were well balanced. Both low PNI (≤45) and high CONUT (≥3) were independent risk factors for poor overall survival (P < 0·05), and the result remained the same after PSM. Survival analysis demonstrated both patients with low PNI and high CONUT score were associated with poorer survival, and the result remained the same after PSM. The results of AUC indicated that CONUT might have a higher sensitivity and specificity in predicting complications and survival. Preoperative low PNI (≤45) and high CONUT (≥3) scores might be reliable predictors of prognosis and surgical complications in PDAC patients. Compared with PNI, CONUT might be more effective.

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, especially in East Asia. ESCC accounts for more than 90% of esophageal cancer. Currently, neoadjuvant therapy in combination with surgical resection is the mainstay of treatment. However, the overall survival rate of patients with locally advanced ESCC is not satisfactory even when treated following the standard treatment guidelines. With neoadjuvant chemoradiotherapy, chemotherapy, or emerging immunotherapy, continuous exploration of efficacy in relation to ESCC is expected to improve overall survival further. Here, we review and summarize current evidence for efficacy of preoperative therapy for locally advanced ESCC., (© 2020 New York Academy of Sciences.)

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue., Method: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis., Result: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22-90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively., Conclusion: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years., (© The Author(s) 2019. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To explore the safety and therapeutic effect of programmed death 1 (PD-1) antibody combined with chemotherapy as a neoadjuvant therapy for patients with stage Ⅱ to Ⅲ non-small cell lung cancer (NSCLC). Methods: Thirteen patients, who had been diagnosed as stage Ⅱ-Ⅲ NSCLC and received PD-1 inhibitor plus chemotherapy as a neoadjuvant treatment in National Cancer Center/Cancer Hospital were recruited. The patients received consecutive neoadjuvant chemotherapy for 21 days as a cycle and the therapeutic efficacy was evaluated after two cycles. Results: At the last time of follow-up on December 2, 2019, the objective response rate (ORR) and disease control rate (DCR) of these patients were 61.5% (95% CI 30.9%-92.1%) and 100%, respectively. The downregulation rate of disease stage was 61.5% (8/13). The resectable rate was 38.5% (5/13), among them, the major pathologic response (MPR) was 60.0% (3/5) and the complete pathologic response (CPR) was 20.0% (1/5). The neoadjuvant chemotherapy displayed a low incidence of adverse reaction. The main grade 3 to 4 toxicities were neutropenia (38.5%) and leukopenia (23.1%). There was no significant immune-related toxicity. The safety and tolerability of perioperative period of patients underwent resection were promising. Conclusions: Immunotherapy combined with chemotherapy as a neoadjuvant treatment is an effective, low-toxicity treatment manner, which has perioperative safety and high rate of MPR for patients with resectable NSCLC. It is a promising treatment option for patients with stage Ⅱ to Ⅲ NSCLC.

Objective: To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China. Methods: A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014. Results: Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusions: The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

Msn2/Msn4-family zinc finger transcription factors play important roles in stress response in yeast. However, some members of this family show significant functional divergence in different species. Here, we report that in the dimorphic yeast Yarrowia lipolytica, the Msn2/Msn4-like protein Mhy1 is a key regulator of yeast-to-hypha dimorphic transition but not stress response. Both MHY1 deletion and overexpression affect filamentation. In contrast, YlMsn4, the other Msn2/Msn4-like protein, regulates tolerance to acid-induced stress. We show that MHY1 has an unusually long (about 3800 bp) promoter featuring an upstream located enhancer and a double stress response element (STRE) motif, the latter of which mediates Mhy1's regulation on its own transcription. Transcriptome profiling conducted in wild-type strain, mhy1Δ mutant and MHY1-overexpressing mutant revealed about 100 genes that are highly differentially expressed (≥ 5-fold) in each of the 2 mutants compared to the wild-type strain. The largest group of genes downregulated in mhy1Δ mutant encodes cell wall proteins or enzymes involved in cell wall organization, suggesting that Mhy1 may regulate dimorphic transition by controlling these cell wall genes. We confirmed that the genes YALI0C23452, YALI0C15268 and YALI0B09955 are directly regulated by Mhy1. We also characterized the Mhy1 consensus binding site as 5'-WNAGGGG-3' (W = A or T; N = A, T, G or C). These results provide new insight in the functions of Msn2/Msn4-family transcription factors in fungi and the mechanism by which Mhy1 regulates dimorphic transition.

Nanodiamonds (NDs) are considered to be relatively safe carbon nanomaterials used for the transmission of DNA, proteins and drugs. The feasibility of utilizing the NDs to deliver CRISPR-Cas9 system for gene editing has not been clearly studied. Therefore, in this study, we aimed to use NDs as the carriers of CRISPR-Cas9 components designed to introduce the mutation in RS1 gene associated with X-linked retinoschisis (XLRS). ND particles with a diameter of 3 nm were functionalized by carboxylation of the surface and covalently conjugated with fluorescent mCherry protein. Two linear DNA constructs were attached to the conjugated mCherry: one encoded Cas9 endonuclease and GFP reporter, another encoded sgRNA and contained insert of HDR template designed to introduce RS1 c.625C>T mutation. Such nanoparticles were successfully delivered and internalized by human iPSCs and mouse retinas, the efficiency of internalization was significantly improved by mixing with BSA. The delivery of ND particles led to introduction of RS1 c.625C>T mutation in both human iPSCs and mouse retinas. Rs1 gene editing in mouse retinas resulted in several pathological features typical for XLRS, such as aberrant photoreceptor structure. To conclude, our ND-based CRISPR-Cas9 delivery system can be utilized as a tool for creating in vitro and in vivo disease models of XLRS. STATEMENT OF SIGNIFICANCE: X-linked retinoschisis (XLRS) is a prevalent hereditary retinal disease, which is caused by mutations in RS1 gene, whose product is important for structural organization of the retina. The recent development of genome editing techniques such as CRISPR-Cas9 significantly improved the prospects for better understanding the pathology and development of treatment for this disease. Firstly, gene editing can allow development of appropriate in vitro and in vivo disease models; secondly, CRISPR-Cas9 can be applied for gene therapy by removing the disease-causative mutation in vivo. The major prerequisite for these approaches is to develop safe and efficient CRISPR-Cas9 delivery system. In this study, we tested specifically modified nanodiamonds for such a delivery system. We were able to introduce Rs1 mutation into the mouse retina and, importantly, observed several XLRS-specific effects., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical features, pathogenesis, diagnosis and scrotal reconstruction in the treatment of idiopathic scrotal calcinosis (ISC)., Methods: From March 2007 to October 2018, 10 ISC patients, aged 28－79 (mean 45) years and with a disease course of 6－497 (mean 128.4) months, were treated in our hospital. We retrospectively analyzed their clinical data and reviewed related literature., Results: All the patients underwent physical examination and biochemical and parathyroid function tests. None of them had a history of endocrine or metabolic disease, or trauma, or a family member with similar diseases, and none had subjective symptoms except local pruritus in 1 case. All were treated surgically and post-operative follow-up revealed no recurrence. Histopathological examination of the excised lesion confirmed it to be ISC., Conclusions: ISC is a rare localized benign disease, of which surgery seems an effective option for the definite diagnosis and treatment. Occasionally scrotal reconstruction may be required in case of extensive involvement of the scrotal skin.

Objective: The role of planned neoadjuvant radiotherapy or chemoradiotherapy in the non-radical resection of esophageal squamous cell carcinoma was unclear. The study aimed to evaluate their therapeutic effect and analyze the prognostic factors. Methods: We retrospectively analyzed the clinical data of locally advanced esophageal squamous cell carcinoma who received neoadjuvant radio therapy (33 patients) and concurrent chemoradiotherapy (119 patients) from January 2004 to December 2016 in our single-institution database.The survival rates were calculated by Kaplan-Meier method. The prognostic factors were analyzed by using Log rank test and Cox proportional hazards model. Results: The median follow-up was 29.8 months. One hundred and one patients survived more than 3 years. The rates of overall survival (OS) and disease-free survival (DFS) at 3 years were 63.9% and 55.6%, respectively.The rates of complete, partial and minimal pathological response of the primary tumor were 50.3%, 38.4%, 11.3%, the corresponding 3-year OS were 75.5%, 57.4%, 27.3% ( P <0.001) and 3-year DFS were 72.0%, 44.7%, 17.6% ( P <0.001), respectively.The postoperative lymph node metastasis rate was 27.0%. The 3-year OS and DFS of the lymph node positive group was 45.6% and 32.8%, significantly lower than 70.8% and 63.7% of the negative group (both P <0.001). The 3-year OS and DFS of pathologic stage Ⅰ, Ⅱ, ⅢA, ⅢB and Ⅵ A were 76.2%, 57.4%, 64.7%, 35.0%, 33.3% ( P <0.001) and 70.1%, 49.3%, 41.2%, 22.1%, 33.3% ( P <0.001), respectively.The operation-related mortality was 3.3%. Multivariate analysis showed that chest pain, postoperative respiratory failure, pathological differentiation, more than 15 lymph node dissection and ypTNM stage were the independent prognostic factors of OS ( P <0.05 for all). Conclusions: The planned neoadjuvant radiotherapy or chemoradiotherapy for the non-radical resection of advanced esophageal squamous cell carcinoma could result in favorable survival. The chest pain, postoperative respiratory failure, pathological differentiation, the number of lymph node resection and ypTNM stage are the independent prognostic factors of the prognosis of these patients.

Esophageal cancer is the sixth leading cause of cancer-related death worldwide due to its high malignancy and poor prognosis. In recent decades, the applications of new technologies, devices and neoadjuvant therapy lead to the great progress in the diagnosis and treatment of esophageal cancer. However, the five-year survival rate of esophageal cancer remains unsatisfied. Clinical and pathological factors such as the primary tumor (T), regional lymph nodes (N) and distant metastasis (M) and the longitudinal margins of esophageal lesions, lymphatic invasion, peripheral nerve invasion have been identified as important predictors of the prognosis of esophageal cancer. However, the effect of circumferential resection margin on the prognosis evaluation of esophageal cancer is still controversial, and no definite identification of circumferential resection margin of esophageal cancer has been acknowledged worldwide. Therefore, the studies of circumferential resection margin involvement in predicting the prognosis of esophageal cancer are reviewed.

Background: The abnormal expression of leucine-rich-alpha-2-glycoprotein 1 (LRG-1) is reported to be associated with multiple malignancies, but its role in the progression of pancreatic ductal adenocarcinoma (PDAC) remains to be determined., Methods: The expression of LRG-1 was assessed in PDAC tissues by RT-PCR, Western blot and immunohistochemistry. LRG-1-silenced or overexpressed cell lines were constructed using shRNA or LRG-1-overexpressing plasmids. EdU incorporation assay, Transwell invasion and wound-healing assays were performed to evaluate the proliferation, invasion and migration of PDAC cells. In addition, protein expression of the mitogen-activated protein kinase (MAPK) pathway was detected using Western blot. Finally, Co-immunoprecipitation assay was conducted in search of the potential interaction between LRG-1 and epidermal growth factor receptor (EGFR)., Results: The expression of LRG-1 in PDAC tissue was significantly higher than that in adjacent normal tissue, and high LRG-1 expression predicted poor survival and a late tumor stage. In addition, LRG-1 markedly promoted the viability, proliferation, migration and invasion of PDAC cells in vitro and facilitated tumor growth in vivo. More importantly, we revealed that these bioactivities of LRG-1 might result from its selective interaction with EGFR, which might further activate the p38/MAPK signaling pathways., Conclusion: LRG-1 may prove to be a promising biomarker for predicting prognosis of PDAC patients. Inhibition of LRG-1 or its downstream pathway could be a potential therapeutic target for the treatment of PDAC.

Three-field lymph node dissection improved the postoperative survival and accuracy of pathological staging of patients with esophageal cancer, and reduced the postoperative local recurrence rate of esophageal cancer patients. However, this surgical procedure enlarged the trauma, cansed more complications, prolonged postoperative hospital stays, and seriously impaired the postoperative adjuvant therapy. Therefore, selection of patients who are suitable for three-field lymph node dissection is extremely important. The special anatomical location of recurrent laryngeal nerve lymph nodes is potentially suitable for it to serve as sentinel lymph node for the evacuation of cervical lymph nodes dissection in esophageal cancer. The guiding value of recurrent laryngeal nerve lymph node metastasis in cervical lymph node dissection of thoracic esophageal cancer is reviewed.

Esophageal cancer is one of the most prevalent cancers in China. Lymph node metastasis is one of the most important prognostic factors and severely affect the long-term survival after surgical treatment. Therefore, systemic two-field lymph node dissection including thoracic and abdominal draining nodes of the esophagus during surgery is essential in order to improve the long-term survival for the patients with thoracic esophageal cancer, and it is also the basis for precise staging and postoperative adjuvant treatment regimen- making. As reported in the literature, lymph node metastases along bilateral recurrent laryngeal nerve was the highest, therefore, the lymph node dissection along bilateral recurrent laryngeal nerve is the most important manipulation during esophagectomies, however, it is also the most technically difficult procedure during operation. It usually results in postoperative complications especially the respiratory complications due to paralysis of recurrent laryngeal nerves caused by lymph node dissection. Therefore, the gain and loss of lymph node dissection along bilateral recurrent laryngeal nerve has been a disputed and entangle topic for thoracic surgeons, and the purpose of this paper is to summarize author's experience and the key technology to prevent the associated complications in lymph node dissection along recurrent laryngeal nerve during esophagectomies for the patients with thoracic esophageal cancer.

Objective: To discuss the affect of glycosylated hemoglobin (HbA1c) level for the onset of nonalcoholic fatty liver disease (NAFLD) in cohort population. Methods: An epidemiological survey of the relationship between HbA1c and NAFLD conducted in 2012 was based at cohort baseline, and three follow-up sessions conducted in 2013, 2014 and 2015. In total 2 811 subjects were included in the study after exclusion of NAFLD patients at baseline and those who lost their lives due to relocation, and death. The Cox proportional hazard model was used to analyze the relationship between glycosylated hemoglobin and other risk factors of NAFLD. Continuous variables were compared using the t -test or the Mann-Whitney test. χ (2)-test was used for the measurement of categorical data. Results: A total of 2 811 subjects with mean age of 59 (58.2±9.8) years old, including 1 664 males and 1 147 females. Age, waist circumference, body mass index, systolic blood pressure, γ-glutamyltransferase and fasting blood glucose level of HbA1c abnormal group were higher than normal group. The incidence of NAFLD in the abnormal HbA1c level group (25.4%) was higher than normal group (14.9 %), and diastolic blood pressure, high-density lipoprotein cholesterol was lower than normal group and the differences were statistically significant. During the three follow-up intervals, there were 440 new cases of NAFLD, consisting 285 males and 155 females with cumulative incidence of 15.7% (440/2 811). Multivariate Cox regression analysis showed that patients with elevated HbA1c had a higher risk of developing NAFLD ( HR 1.796; 95% CI 1.335~2.418; P < 0.01), and the increased HbA1c level after adjustment for gender, age, and metabolic syndrome-related factors remained an independent risk factors for NAFLD ( HR 1.580; 95.0% CI 1.161-2.152; P < 0.01). Conclusion: An elevated HbA1c levels have a positive predictive value for the onset of NAFLD.

Background: Esophageal cancer is one of the most prevalent malignancies with a high incidence and mortality in China, the main treatment for esophageal cancer at present is still surgery-based multimodality treatment, and surgery is still the most effective measure. However, the modes of surgical treatment for esophageal cancer have been diverse. The surgical approaches can be mainly divided into the left thoracic approach and right thoracic approach in China. The long-term survival of the patients treated through right approach was reported better than that through left thoracic approach, but until now no statistically significant difference was found between two approaches, especially, for those with middle and lower thoracic esophageal cancer without suspected upper mediastinal lymph node metastasis in preoperative examinations, no definite conclusion have been made on selection of the approach, therefore, this studies try to compare the long-term survival between two approaches ., Methods: The data of 402 cases with complete resection and two-field lymph node dissection from January, 2011 to December, 2011 in the Cancer Hospital, Chinese Academy of Medical Sciences was retrospectively reviewed and analyzed. Propensity score matching (PSM) analysis and life-table in SPSS 22.0 and Stata 14.0 were used to analyze the survival., Results: Totally, 402 cases were surgically treated either via left or right thoracic approach. The overall 5-year survival rate of this series was 38%, it was 37% in 281 cases surgically treated through left approach, and 39% in 121 cases through right approach (P=0.908). The 5-year survival of 256 patients without suspected lymph node metastasis in the upper mediastinum based on the preoperative examinations surgically treated through left approach was 38% versus 43% of 88 cases through right approach (P=0.404). After PSM, the 5-year survival of 110 cases surgically treated through left approach was 32% versus 40% of another matched 110 cases through right approach (P=0.146). for the patients without suspected lymph node metastasis in the upper mediastinum based on preoperative examinations, the 5-year survival of 88 surgically treated through left approach was 33% versus 44% of another matched 88 cases through right approach (P=0.239)., Conclusions: For the middle and lower thoracic esophageal cancer patients, whether or not who has suspected lymph node metastasis in the upper mediastinum based on preoperative CT and EUS, the surgical treatment through right thoracic approach can achieve better but not significantly better overall survival than that through left thoracic approach. Further prospective randomized clinical trials are still needed to verify this disputed issue on approach selection., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Objective: To study the impact of the advance of the times and technological progress on the surgical treatment of lung cancer. Methods: The data of patients with non-small cell lung cancer treated by thoracic surgery at Cancer Hospital of Chinese Academy of Medical Sciences from 2005 to 2015 were retrospectively analyzed. The population distribution, operation methods and treatment results were analyzed retrospectively. Results: 510 patients (in 2005) and 1 235 (in 2015) non-small cell lung cancer patients were included in this study. The proportions of male patients (79.0% vs. 55.8%), smoking (52.9% vs. 30.1%), squamous cell carcinoma (50.2% vs. 22.4%) and video-assisted thoracoscopic surgery (VATS) (0 vs. 61.1%), stage Ⅰ (15.2% vs. 36.8%), the number of lymph node dissection (21.8 vs. 16.6), intraoperative blood transfusion rate (9.6% vs. 1.9%), palliative resection rate (7.5% vs. 2.0%), the average length of stay (10.8 d vs. 7.6 d) were significantly changed. There was no significant difference in the average age of patients and operation time. Conclusion: There was a significant change in the distribution of population and surgical techniques in patients undergoing lung cancer surgery in last ten years.

Objective: To investigate the diagnosis and management of penile fracture., Methods: From June 1993 to May 2017, 46 cases of penile fracture were treated in our hospital, averaging 33.5 (25－42) years of age and 3.45 (1－10) hours in duration, of which 41 occurred during sexual intercourse, 4 during masturbation and 1 during prone sleeping, 4 with hematuria, but none with dysuria or urethral bleeding. Hematoma was confined to the penis. Emergency surgical repair was performed for all the patients, 45 under spinal anesthesia and 1 under local anesthesia, 16 by coronal proximal circular incision and the other 30 by local longitudinal incision according to the rupture location on ultrasonogram. The tunica albuginea ruptures averaged 1.31 (0.5－2.5) cm in length, which were sutured in the "8" pattern for 6 cases and with the 3－0 absorbable thread for 18 cases. The skin graft or negative pressure drainage tube was routinely placed, catheters indwelt, and gauze used for early pressure dressing. In the recent few years, elastic bandages were employed for 3－5 days of pressure dressing and antibiotics administered to prevent infection. The stitches and catheter were removed at 7 days after surgery., Results: Short-term postoperative foreskin edema occurred in 14 of the 16 cases of circular degloving incision, but no postoperative complications were observed in any of the cases of local incision. Twenty-eight of the patients completed a long-term follow-up of 49.4 (10－125) months, which revealed good erectile function, painless erection, and satisfactory sexual intercourse., Conclusions: For most penile fractures, local longitudinal incision is sufficient for successful repair of the tunica albuginea, with mild injury, no influence on the blood supply or lymph reflux, and a low rate complications. It therefore is obviously advantageous over circular degloving incision except when the cavernous body of urethra is to be explored, which necessitates circular degloving incision below the coronal groove.

Breast cancer-specific gene 1 (BCSG1), also referred to as γ-synuclein (SNCG), is highly expressed in human infiltrating breast carcinomas, but not in normal or benign breast tissue. The present study aimed to evaluate the effects of BCSG1 siRNA delivered by lentiviral vector on breast cancer cells and investigate the underlying mechanisms. BCSG1 RNAi lentiviral vector was constructed and transfected into MDA-MB-231 cells. BCSG1 mRNA levels were determined by quantitative polymerase chain reaction analysis. Cell proliferation, migration and apoptosis were evaluated by using the cell counting kit‑8, Transwell assay and flow cytometry, respectively, followed by western blotting to determine the relative levels of AKT, extracellular signal‑regulated kinase (ERK), p-AKT and p-ERK expression. BCSG1 mRNA levels were significantly reduced in MDA-MB‑231 cells following transfection of BCSG1 siRNA delivered by lentiviral vector. Cell migration and proliferation were significantly decreased and the cell cycle was arrested. Western blot analysis indicated that the protein levels of p-AKT and p-ERK were significantly lower in the BCSG1 siRNA-treated groups compared with the control and negative control groups. Therefore, BCSG1 siRNA delivered by lentiviral vector was able to significantly reduce BCSG1 expression, suppress cell migration and proliferation, possibly through the reduction of the protein levels of p-AKT and p-ERK.

The MALAT1 (Metastasis-Associated Lung Adenocarcinoma Transcript 1) gene encodes a noncoding RNA that is processed into a long nuclear retained transcript (MALAT1) and a small cytoplasmic tRNA-like transcript (mascRNA). Using an RNA sequence- and structure-based covariance model, we identified more than 130 genomic loci in vertebrate genomes containing the MALAT1 3' end triple-helix structure and its immediate downstream tRNA-like structure, including 44 in the green lizard Anolis carolinensis. Structural and computational analyses revealed a co-occurrence of components of the 3' end module. MALAT1-like genes in Anolis carolinensis are highly expressed in adult testis, thus we named them testis-abundant long noncoding RNAs (tancRNAs). MALAT1-like loci also produce multiple small RNA species, including PIWI-interacting RNAs (piRNAs), from the antisense strand. The 3' ends of tancRNAs serve as potential targets for the PIWI-piRNA complex. Thus, we have identified an evolutionarily conserved class of long noncoding RNAs (lncRNAs) with similar structural constraints, post-transcriptional processing, and subcellular localization and a distinct function in spermatocytes., (Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Thymoma is an uncommon tumor without a widely accepted standard care to date. We aimed to investigate the clinicopathologic variables of patients with thymoma and identify possible predictors of survival and recurrence after initial resection., Methods: We retrospectively selected 307 patients with thymoma who underwent complete resection at the Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (Beijing, China) between January 2003 and December 2014. The associations of patients' clinical characteristics with prognosis were estimated using Cox regression and Kaplan-Meier survival analyses., Results: During follow-up (median, 86 months; range, 24-160 months), the 5- and 10-year disease-free survival (DFS) rates were 84.0% and 73.0%, respectively, and the 5- and 10-year overall survival (OS) rates were 91.0% and 74.0%, respectively. Masaoka stage (P < 0.001), World Health Organization (WHO) histological classification (P < 0.001), and postoperative radiotherapy after initial resection (P = 0.006) were associated with recurrence (52/307, 16.9%). Multivariate analysis revealed that, after initial resection, WHO histological classification and Masaoka stage were independent predictors of DFS and OS. The pleura (25/52, 48.0%) were the most common site of recurrence, and locoregional recurrence (41/52, 79.0%) was the most common recurrence pattern. The recurrence pattern was an independent predictor of post-recurrence survival. Patients with recurrent thymoma who underwent repeated resection had increased post-recurrence survival rates compared with those who underwent therapies other than surgery (P = 0.017)., Conclusions: Masaoka stage and WHO histological classification were independent prognostic factors of thymoma after initial complete resection. The recurrence pattern was an independent predictor of post-recurrence survival. Locoregional recurrence and repeated resection of the recurrent tumor were associated with favorable prognosis.

Objective: To analyze risk factors of anastomotic leakage after McKeown'sesophagectomy. Methods: The clinical data of 635 esophageal cancer patients, who underwent McKeown's esophagectomy at Cancer Hospital of Chinese Academy of Medical Sciences from January 2012 to December 2015, were retrospectively analyzed. The risk factors of cervical anastomotic leakage were identified through analysis of medical history, surgical procedure, tumor characteristics and vascular calcification. Results: Among all the 635 patients, anastomotic leakage occurred in 111 (17.5%)patients. Univariate analysis showed that the American Society of Anesthesiologists (ASA) risk class, prior thoracic surgery, upper digestive tract ulcer, COPD, hypertension, peripheral vascular disease, renal insufficiency, FEV1% predicted, DLCO% predicted, duration of surgery and calcification of descending aorta, celiac trunk and left postceliac arteries were associated with a statistically significant increase in risk of cervical anastomotic leakage ( P <0.05 for all). Logistic regression analysis showed that ASA risk class, peripheral vascular disease, renal insufficiency and calcification of descending aorta and celiac trunk were independent risk factors of cervical anastomotic leakage after McKeown's esophagectomy ( P <0.05 for all). Conclusions: ASA risk class, peripheral vascular disease, renal insufficiency, calcification of descending aorta and celiac trunk are independent risk factors of cervical esophageal anastomotic leakage after McKeown's esophagectomy.

Objective: To evaluate the feasibility and efficacy of biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma. Methods: We retrospectively analyzed the clinicopathological data of 20 patients with esophageal squamous cell carcinoma treated in our hospital between January 2012 and March 2016. All patients received biweekly paclitaxel and platinum chemotherapy followed by surgery. Results: 20 cases received preoperative chemotherapy for 3-8 cycles with an average of 4 cycles. The main chemotherapy-related adverse events were bone marrow suppression (18/20, 90.0%), followed by vomiting and nausea (10/20, 50.0%). Five patients (25.0%) had grade 4 neutropenia and all toxicities were torlerable and manageable. After chemotherapy, all patients received surgery. The histological responses in the primary tumors were grade 1 in 13 (65.0%) patients, grade 2 in 7 (35.0%) patients, and grade 3 in 0 (0%) patient. None had disease progression. Downstaging of T-stage was observed in 5 cases (25.0%) after chemotherapy. Among them, 4 cases were with moderate histologicl responses and one case with mild histological response. The incidence of postoperative complications was 25.0%(5/20), and the complications were improved following symptomatic treatments. There was no treatment-related death. Conclusions: Biweekly paclitaxel and platinum chemotherapy followed by surgery for esophageal squamous cell carcinoma is safe and effective. Further randomized clinical trial should be conducted to assess the value of this therapeutic regimen in the preoperative chemotherapy for esophageal cancer.

Possible association between Helicobacter pylori infection (HPI) and nonalcoholic fatty liver disease (NAFLD) has been proposed by several studies with inconsistent conclusions. Here, we studied the association between HPI and NAFLD at 3 levels: (i) genetic level; (ii) small molecular level; and (iii) clinical level. Relation data between diseases, genes, and small molecules were acquired from Pathway Studio ResNet Mammalian database. Clinical data were acquired from 2263 elderly South Chinese subjects, including 603 NAFLD patients and 1660 subjects without NAFLD. Results showed that HPI and NAFLD present significantly shared genetic bases (95 genes, p value = 2.5E-72), demonstrating multiple common genetic pathways (enrichment p value ≤ 4.38E-20 for the top 10 pathways). Genetic network analysis suggested that mutual regulation may exist between HPI and NAFLD through 21 out of 95 genes. Furthermore, 85 out of the 95 genes manifested strong interaction with 12 small molecules/drugs that demonstrate effectiveness in treating both diseases. Clinical results showed that HPI rate in the NAFLD group was significantly higher than that in the group without NAFLD (51.9% vs. 43.6%; p value = 4.9E-4). Multivariate logistic regression results supported the observations and suggested that HPI served as a risk factor for NAFLD in the experiment data studied (odds ratio: 1.387, p value = 0.018). Results from this study support the hypothesis that complex biological association may exist between HPI and NAFLD, which partially explains the significant clinical co-incidence in the elderly population of south China.

Background: The aim of this study was to compare the short-term outcomes and three-year survival between dual-incision esophagectomy (DIE) and total minimally invasive McKeown esophagectomy (MIME) for esophageal cancer patients with negative upper mediastinal lymph nodes requiring esophagectomy and neck anastomosis., Methods: One hundred and fifty patients underwent DIE, while 361 patients received total MIME. Perioperative outcomes and three-year survival were compared in unmatched and propensity score matched data between two groups., Results: Both unmatched and matched analysis demonstrated that there were no significant differences in the number of lymph nodes harvested, or major or minor complication rates between the DIE and MIME groups. Compared with patients who underwent DIE, patients who underwent total MIME had longer operation duration (310 minutes vs. 345 minutes; P  = 0.002). However, there was significantly less intraoperative blood loss in the total MIME compared with the DIE group (191 mL vs. 287 mL, respectively; P  < 0.001). Kaplan-Meier analysis demonstrated a trend that patients who underwent MIME had longer overall (79.5% vs. 64.1%; P  = 0.063) and disease-free three-year survival (65.3% vs. 82.8%; P  = 0.058) compared with patients who underwent DIE., Conclusions: Both total MIME and DIE are feasible for the surgical treatment of esophageal cancer patients with negative upper mediastinal lymph nodes requiring esophagectomy and neck anastomosis. However, MIME was associated with better overall and disease-free three-year survival compared with DIE., (© 2017 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

The major depressive disorder (MDD) is a relatively common mental disorder from which that hundreds of million people have suffered, leading to displeasing life quality, which is characterized by health damage and even suicidal thoughts. The complicated development and functioning of MDD is still under exploration. Long noncoding RNA (lncRNAs) are highly expressed in the brain, could affect neural stem cell maintenance, neurogenesis and gliogenesis, brain patterning, synaptic and stress responses, and neural plasticity. The dysregulation of certain lncRNAs induces in neurodevelopmental, neurodegenerative and neuroimmunological disorders, primary brain tumors, and psychiatric diseases. Although advances have been made, no fully satisfactory treatments for major depression are available, further investigation is requested. And recently data showed that the expression level of the majority of lncRNAs demonstrated a clear tendency of upregulation, and the certain dysregulated miRNAs and lncRNAs in the MDD have been proved to have a co-synergism mechanism, that is why we speculate lncRNA might get the capability to regulate MDD. Few identified lncRNAs have been deeply studied in detailed experiments up until now, little predictions of their function have been raised, and further researches is calling for discover their signal pathway and related regulatory networks., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: The aim of this study was to investigate the perioperative outcomes and 3-year overall survival (OS) of 2 approaches including Sweet and open Ivor Lewis esophagectomy in the surgical treatment of middle and lower third esophageal squamous cell carcinoma., Methods: The medical records of 1,746 consecutive patients who underwent esophagectomy for middle and lower esophageal cancer between January 2009 and September 2015 at the First Department of Thoracic Oncologic Surgery of Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College were retrospectively reviewed. The clinical variables and 3-year survival were compared between Sweet (n=1,701) and open Ivor Lewis (n=45) approaches in unmatched and propensity score matching analysis., Results: Patients who received esophagectomy by Sweet approach had shorter duration of surgery (mean 212 vs. 390 min; P<0.001), more lymph nodes removed (mean 24 vs. 19; P=0.005), lower overall complications rate (24.4% vs. 11.7%; P=0.009), lower total hospital cost (¥77,200 vs. 106,000; P=0.045) compared with patients who received open Ivor Lewis approach. After propensity score matching analysis, Sweet approach was still associated with decreased duration of surgery (mean 210 vs. 390 min; P<0.001), more lymph nodes removed (mean 24 vs. 19; P=0.050), and lower total hospital cost (¥86,800 vs. 106,000; P=0.045) compared with Ivor Lewis approach. However, there were no significant differences in overall complication rates (24.4% vs. 24.4%; P=1.000) between two approaches. There was no significant difference in 3-year OS between Sweet and open Ivor Lewis approaches (59.9% vs. 61.4%; P=0.637) in unmatched analysis and in matched analysis (77.8% vs. 61.4%; P=0.264)., Conclusions: In this cohort, for middle and lower third esophageal squamous cell carcinoma patients, both Sweet and open Ivor Lewis approaches are feasible in terms of perioperative outcomes and 3-year OS., Competing Interests: The authors have no conflicts of interest to declare.

Background: The prognostic value of serum lactate dehydrogenase (LDH) has been demonstrated in various solid tumors. We attempted to determine whether serum LDH was predictive of survival in thymic carcinoma after surgical resection., Methods: Ninety-five patients with thymic carcinoma treated in our hospital between January 2005 and December 2015 were retrospectively enrolled. Serum LDH was measured before surgery and categorized as low or high relative to the upper limit of normal (ULN) (225 U/L). The relationships of serum LDH level and other clinical variables with survival were estimated by Cox regression and Kaplan-Meier survival analysis., Results: Serum LDH levels were found to be significantly associated with overall survival (OS) and progression-free survival (PFS) of these patients. The 1-, 3-, and 5-year PFS were 76%, 51%, and 38%, and the 1-, 3- and 5-year OS were 97%, 75%, and 46%, respectively. Univariate analysis found that high serum LDH (>225 U/L) was associated with both lower OS [hazard ratio (HR) =2.710; 95% confidence interval (CI): 1.363-1.5.391; P=0.004] and PFS (HR =3.365; 95% CI: 1.776-6.374; P<0.001). Multivariate analysis found that high serum LDH was associated with lower PFS (HR =2.122; 95% CI: 1.056-4.267; P=0.035). Moreover, high LDH was significantly associated with advanced Masaoka stage (P=0.001)., Conclusions: High serum LDH (>225 U/L) was an independent predictor of decreased PFS in thymic carcinoma patients. It was also significantly associated with reduced OS, but was not an independent predictor of death in those patients., Competing Interests: The authors have no conflicts of interest to declare.

Background: To summarize our experiences of single-port, two-port vs. three-port VATS pulmonary resection for lung cancer patients., Methods: Data of consecutive 1,553 patients who underwent video assisted thoracoscopic surgery (VATS) pulmonary resection for lung cancer in the Department of Thoracic Surgery of Cancer Hospital of Chinese Academy of Medical Sciences and Peking Union Medical College between November 2014 and January 2016 were prospectively collected and analyzed. A propensity-matched analysis was used to compare the short-term outcomes of lung cancer patients who received VATS single-port, two-port and three-port pulmonary resection., Results: There were 716 males and 837 females. The mean age was 58.90 years (range, 25-82 years) and the conversion rate was 2.7% (42/1,553) in this cohort. After propensity score matching, there were 207 patients in single-port and two-port group, and 680 patients in three-port group. Propensity-matched analysis demonstrated that there were no significant differences in duration of operation (129 vs. 131 min, P=0.689), intra-operative blood loss (63 vs. 70 mL, P=0.175), number of dissected lymph nodes (12 vs. 13, P=0.074), total hospital expense (﹩9,928 vs. ﹩9,956, P=0.884) and cost of operation (﹩536 vs. ﹩535, P=0.879) between VATS single-port, two-port and conventional three-port pulmonary resection groups. There was no significant difference in the complication rate between two groups (5.3% vs. 4.7%, P=0.220). However, compared with three-port group, patients who underwent single port and two-port experienced shorter postoperative length of stay (6.24 vs. 5.61 d, P=0.033), shorter duration of chest tube (4.92 vs. 4.25 d, P=0.008), and decreased volume of drainage (926 vs. 791 d, P=0.003)., Conclusions: The short term outcomes between VATS single-port, two-port and conventional three-port groups for the surgical treatment of lung cancer were comparable. However, compared with three-port VATS pulmonary resection, single-port and two-port were associated with shorter postoperative length of stay, shorter duration of chest tube, and decreased volume of drainage.

Background: Preoperative neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) have prognostic value in patients with various operable tumors. The aim of our study was to determine whether NLR and PLR are predictive of survival in thymic carcinoma patients after complete resection., Methods: A total of seventy-nine patients who underwent complete resection of thymic carcinoma at our hospital between January 2005 and December 2015 were retrospectively enrolled. Differential leukocyte counts were collected before surgery, and the relationships of NLR, PLR, and other patient clinical variables with survival were estimated by Cox regression analysis and Kaplan-Meier survival analysis., Results: Univariate analysis found that a high level of NLR was associated with lower disease-free survival (DFS) (HR: 3.385, 95% CI: 1.073-10.678, P=0.037) and lower overall survival (OS) (HR: 12.836, 95% CI: 1.615-101.990, P=0.016). The optimal NLR threshold of 4.1 could stratify the patients with high risk of recurrence or metastasis (P=0.026) and death (P=0.006). Meanwhile, the NLR value of >4.1 in those patients was associated with bigger tumor size (P=0.035) and more advanced Masaoka stages (P=0.040) compared with NLR ≤4.1. However, the PLR and other variables were not significantly associated with survival in thymic carcinoma patients., Conclusions: The preoperative NLR of >4.1 was significantly associated with larger tumor size, more advanced Masaoka stages and reduced DFS and OS, but was not an independent predictor of survival in thymic carcinoma patients after complete resection.

Objective: To explore the clinical characteristics of patients with bilateral synchronous multiple primary non-small cell lung cancer (NSCLC) and identify the prognostic indicators associated with survival., Methods: From January 2010 to December 2014, clinicopathological data of 96 patients with bilateral synchronous multiple primary NSCLC, who met the modified Martini-Melamed criteria and underwent radical surgical resection, were retrospectively reviewed. Survival was estimated using the Kaplan-Meier method, and the clinical parameters associated with survival were analyzed using a log-rank test. Cox proportional hazards regression models were used to identify the risk factors for this cancer., Results: Of the 96 patients, two patients who died of severe postoperative complications were excluded, and 94 patients were analyzed. Of the 94 cases, a two-stage operation was performed in 93 patients, while a single-stage bilateral surgery was performed in only one patient using video-assisted thoracic surgery (VATS). 79 patients had 2 tumors and the other 15 patients had 3 or more tumors. There were 82 patients with synchronous tumors located in different lobes and 12 patients had at least two tumors located in the same lobe. Seventy-six patients were found to have multiple lung adenocarcinoma and 12 patients had multiple squamous cell carcinoma (SCCs). Five patients had adenocarcinoma and SCC, and one patient had adenocarcinoma and adenosquamous carcinoma simultaneously. Univariate analysis showed that the large maximum tumor diameter, highest pT stage and lymph node involvement were associated with an unfavorable DFS (P<0.01 for all), while female gender, small maximum tumor diameter, early highest pT stage and pN0 were associated with a better overall survival (OS). Multivariate analysis showed that highest pT stage and lymph node metastasis were independent prognostic factors for DFS and OS. Patients with a lower highest pT stage and negative lymph node metastasis had longer DFS and OS (P<0.05 for both)., Conclusions: The diagnosis for patients with bilateral synchronous multiple primary NSCLCs should be made very carefully. Two stage surgical treatment is safe, reasonable and effective for patients with bilateral synchronous multiple primary NSCLCs in a relatively early stage. The highest pT stage and pN status are important predictors for long-term survival. Adequate pulmonary tissue resection with complete resection of multiple nodules and systematic lymphadenectomy are suggested.

Aim: To update our experiences with minimally invasive McKeown esophagectomy for esophageal cancer., Methods: We retrospectively reviewed the medical records of 445 consecutive patients who underwent minimally invasive McKeown esophagectomy between January 2009 and July 2015 at the Cancer Hospital of Chinese Academy of Medical Sciences and used 103 patients who underwent open McKeown esophagectomy in the same period as controls. Among 375 patients who underwent total minimally invasive McKeown esophagectomy, 180 in the early period were chosen for the study of learning curve of total minimally invasive McKeown esophagectomy. These 180 minimally invasive McKeown esophagectomies performed by five surgeons were divided into three groups according to time sequence as group 1 (n = 60), group 2 (n = 60) and group 3 (n = 60)., Results: Patients who underwent total minimally invasive McKeown esophagectomy had significantly less intraoperative blood loss than patients who underwent hybrid minimally invasive McKeown esophagectomy or open McKeown esophagectomy (100 mL vs 300 mL vs 200 mL, P = 0.001). However, there were no significant differences in operation time, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between total minimally invasive McKeown esophagectomy, hybrid minimally invasive McKeown esophagectomy and open McKeown esophagectomy groups. There were no significant differences in 5-year survival between these three groups (60.5% vs 47.9% vs 35.6%, P = 0.735). Patients in group 1 had significantly longer duration of operation than those in groups 2 and 3. There were no significant differences in intraoperative blood loss, number of harvested lymph nodes, or postoperative morbidity including incidence of pulmonary complication and anastomotic leak between groups 1, 2 and 3., Conclusion: Total minimally invasive McKeown esophagectomy was associated with reduced intraoperative blood loss and comparable short term and long term survival compared with hybrid minimally invasive McKeown esophagectomy or open Mckeown esophagectomy. At least 12 cases are needed to master total minimally invasive McKeown esophagectomy in a high volume center.