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Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to “leak” into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.

Background Thousands of papers on testicular germ cell tumor (TGCT) have been published over the past two decades. This study aimed to assess the key topics and future trends in TGCT research from a comprehensive perspective. Methods All literature defined as review and article type on TGCT published between 2000 and 2020 was identified and retrieved from the Web of Science Core Collection (WoSCC) database. Bibliometric analysis was conducted by the online analysis platform and VOSviewer (version 1.6.16). The key directions and future trends in the research field of TGCT were evaluated using Bibliographic Item Co-occurrence Matrix Builder (version 2.0) and gCLUTO software. Results Ultimately, a total of 4,550 papers between 2000 and 2020 were included in the field of TGCT. The leadership of the United States in global TGCT research with 1,549 publications during the last two decades was obvious. The Indiana University was the most productive institution with 360 publications, and it was also the institution most frequently involved in research cooperation. Journal of Urology published the highest number of publications on TGCT. Looijenga LHJ, Bokemeyer C, Ulbright TM, Sheinfeld J and Dieckmann KP were the top productive contributors to TGCT research. Further, five research hotspots have been identified: (I) epidemiology of TGCT; (II) TGCT-related infertility; (III) pathological classification with TGCT; (IV) management options for TGCT; and (V) Prevention of cancer metastasis in TGCT patients. Conclusions During the last two decades, the United States was a global leader, and research hotspots included epidemiology, male infertility, pathology, and therapy in the field of TGCT. Furthermore, the genetics mechanisms and cisplatin resistance will remain hotspots in future TGCT research.

Liposarcoma is a rare malignant tumor type and surgical resection is the gold standard treatment. The present study reported on the case of a 51-year-old woman who presented with a mass in the left upper abdomen. Computed tomography revealed a 32-cm giant retroperitoneal liposarcoma. Complete tumor resection was performed without the removal of other organs. Postoperative pathological examination indicated retroperitoneal well-differentiated liposarcoma and immunohistochemistry revealed S-100(-), MDM2(+), vimentin(+), CDK4(+), p16(+) and STAT6(+) results. The patient recovered well after the surgery. Complete tumor resection during the first surgery is key to cure liposarcoma. The present case report will be helpful for clinical oncologists to fully understand giant retroperitoneal liposarcoma and treat it accordingly.

Zhenming Zhang,1,* Zhentao Hu,1,* Yujie Qin,2,* Jun Qian,3 Song Tu,1,3 Jiaxi Yao3,4 1Department of General Surgery II, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 2Department of Endoscopy Center, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 3Institute of Urology, Hexi University, Zhangye, Gansu, 734000, People’s Republic of China; 4Department of Urology, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxi Yao; Song Tu, Department of Urology, Zhangye People’s Hospital, affiliated to Hexi University, No. 67, Xihuan Road, Ganzhou District, Zhangye City, Gansu, 734000, People’s Republic of China, Tel +86-18093616382, Email 16111210057@fudan.edu.cn; zytusong@126.comPurpose: To determine an accurate method of inspecting low anastomotic leakages and application of transurethral prostate resection instrumentation for treating low rectal anastomotic leakage.Patients and Methods: Clinical data of eight patients treated for anastomotic leakage after rectal cancer surgery at Zhangye People’s Hospital (affiliated to Hexi University), from August 2019 to November 2021, were retrospectively analyzed. Transanal prostate resection instrumentation was used to assess the leakage and surrounding conditions. Using prostate resection instrumentation, the presacral and perirectal residual cavities were washed and removed, and indwelling suprapubic presacral, transanal presacral, and rectal drainage tubes were placed. Continuous presacral saline irrigation and drainage and open negative-pressure suction in the rectal cavity were performed until the patients’ fistula healed.Results: Of the eight patients with anastomotic leakages, one had grade B and seven had grade C International Study Group of Rectal Cancer anastomotic leakage classifications following Dixon operation. Transanal prostate resection instrumentation showed that the leakage of the one patient with grade B was less than a third of the circumference of the anastomosis. Among the seven patients with grade C, one leakage was less than a third of the anastomotic circumference. One patient had complete separation of the anastomosis and one distal colon necrosis, which necessitated immediate descending colostomy. Conservative treatment was successful in six patients; the conservative overall cure rate was 75%, and the median healing time was 43 (21– 68) days.Conclusion: Transanal examination of rectal anastomotic leakage using prostate resection instrumentation is comprehensive, easy to perform, provides clear visualization, accurately guides catheter placement, and can be combined with continuous open negative-pressure drainage, which is a safe, convenient, and effective method for treating low rectal leakage.Keywords: anastomotic leakage, prostate resection instrumentation, catheter, negative-pressure drainage

Introduction Complement C5a is an important component of the innate immune system. An increasing number of reports have revealed the relevance of C5a in tumor progression; however, its exact role in metastatic renal cell carcinoma (mRCC) remains unknown. Methods We evaluated C5a expression in tumor tissue microarrays of 231 mRCC patients and analyzed the relationship between C5a levels and clinical outcomes, and the expression of epithelial-mesenchymal transition (EMT)-related proteins, programmed cell death protein 1 (PD-1), and programmed cell death-ligand 1 (PD-L1). In-vitro functional experiments using exogenous C5a stimulation and C5a silencing in renal cell carcinoma cells were used to validate the tissue findings. Results High C5a expression was associated with poor therapeutic responses, poor overall and progression-free survival, and high expression of EMT-related proteins and PD-1/PD-L1 in mRCC patients. Exogenous C5a promoted proliferation, migration, and invasion of renal cell carcinoma cells, and induced the expression of EMT-related proteins and PD-1/PD-L1. Conversely, C5a silencing inhibited migration and invasion of renal cell carcinoma cells and decreased the expression of EMT-related proteins and PD-1/PD-L1. Conclusions Our findings indicate that elevated C5a expression is associated with poor outcomes in patients with mRCC, and this effect may be partly attributed to the ability of C5a to promote EMT and PD-1/PD-L1 expression. C5a may be a potential novel target for the treatment of mRCC.

Serum protein fraction (SPF) is a common parameter reflecting the nutritional and inflammatory status of the human body. However, its role in patients with cancer, particularly those treated with targeted agents, is unknown. We conducted this study to explore the prognostic value of SPF in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors and its association with clinical characteristics. Patients with mRCC (n = 213) who initiated first-line sunitinib or sorafenib systemic therapy for metastatic disease between March 2007 and June 2017 at Zhongshan Hospital, Fudan University, were retrospectively included in our analysis. Clinical and pathological data were collected. SPF was measured by capillary electrophoresis. Prognostic factors of overall survival (OS) and progression-free survival (PFS) were analyzed using the Cox proportional hazards model. Correlation was estimated with Spearman’s correlation coefficient. Among all SPF components, high α1-globulin was an independent prognostic factor for OS and PFS (dichotomized by median, hazard ratio [HR] 2.356; 95% confidence interval [CI] 1.399–3.966, p = 0.001; and HR 1.994; 95% CI 1.360–2.923, p

Tumour-infiltrating mast cells (TIMs) have been reported to play functional roles in the tumour microenvironment. However, controversial evidences exist regarding their impact in different cancers. In order to study their role in metastatic renal cell carcinoma (mRCC), we have investigated the prognostic value of TIMs and their association with tumour-infiltrating lymphocytes (TILs) in patients with mRCC treated with sunitinib or sorafenib. Baseline clinical characteristics and follow-up data were collected from 231 patients with mRCC; TIMs (mast cells density positive to tryptase), along with CD8+ and CD4+ TILs, were evaluated by immunohistochemistry using a tissue microarray. The log-rank test and univariate and multivariate COX regression models were used for survival analyses. Our results revealed that patients with high mast cell density had significantly better overall and progression-free survival (OS, P = .008, and PFS, P = .016, respectively) than those with low mast cell density. Additionally, multivariate COX regression analyses identified TIMs as an independent prognostic factor for OS (HR = 0.624, 95% CI: 0.420-0.927, P = .020) and PFS (HR = 0.658, 95% CI: 0.466-0.930, P = .019). Further, combining TIMs with the International mRCC Database Consortium (IMDC) risk model achieved statistically significant and better predictive ability for one- and two-year OS (P = .002 and P = .004, respectively). Moreover, the cases with high mast cell density were associated with a high density of CD8+ and CD4+ TILs (P = .008 and P = .001, respectively). Thus, better OS in patients with mRCC exhibiting a high mast cell density population may be attributed to the co-existence of CD8+ and CD4+ TILs, which have anti-tumour effects on activation status.

Bladder cancer (BC) is one of the most common malignancies in terms of incidence and recurrence worldwide. The aim of this study was to identify novel prognostic biomarkers related to BC progression utilizing weighted gene co-expression network analysis (WGCNA) and further bioinformatic analysis. First, we constructed a co-expression network by using WGCNA among 274 TCGA-BLCA patients and preliminarily screened out four genes (CORO1C, TMPRSS4, PIK3C2B, and ZNF692) associated with advanced clinical traits. In support, GSE19915 and specimens from 124 patients were used to validate the genes selected by WGCNA; then, CORO1C and TMPRSS4 were confirmed as hub genes with strong prognostic values in BC. Moreover, the result of gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) indicated that CORO1C and TMPRSS4 might be involved in the process of epithelial to mesenchymal transition (EMT) reversely. In addition, high expression of CORO1C was found to be significantly correlated with tumor-infiltrating neutrophils (TINs), a negative regulatory component that facilitates tumor distant progression and induces poor clinical outcome. In conclusion, our study first identified CORO1C and TMPRSS4 as vital regulators in the process of tumor progression through influencing EMT and could be developed to effective prognostic and therapeutic targets in future BC treatment.

Background Gastric lavage (GL) is one of the most critical early therapies for acute paraquat (PQ) poisoning; however, details of the treatment protocol remain to be established. Methods A rapid quantitative method involving sodium dithionite testing was developed. It was validated for the determination of the PQ concentrations in gastric juice and eluate samples from a swine acute PQ poisoning model with early or delay GL, or without. The vital signs, laboratory testing, and PQ plasma concentrations were collected for therapeutic effect evaluation. Results The reaction conditions of the test were optimized for two types of samples. Early GL at one hour (H1) could improve the signs and symptoms after acute PQ poisoning at 24 hours (H24). In contrast, GL at 6 hours (H6) could only partially relieve the vital signs. The H1 GL group effectively reduced the peak of the plasma PQ concentration. In addition, the PQ concentrations in the plasma and the gastric juice were significantly decreased in both the GL groups as compared to the untreated group at H24. Moreover, there was no significant difference in the washing efficiencies calculated from the total eluates between the two GL groups. However, the washing efficiency of the first 10 L eluate is superior to that of the additional 10 L eluate. Conclusion GL only at early stage may it benefit PQ poisoning in an animal model. The currently used 20 L GL volume may need to be reduced in view of the low washing efficiency in the later 10 L eluate. The rapid quantitative method can be used for gastric juice sample and has a certain value for clinical GL practices.

The aim of this study was to investigate the effects of chromatin-remodeling genes on the prognosis of patients with clear cell renal cell carcinoma (ccRCC). In TCGA-KIRC patients, two subgroups based on 86 chromatin-remodeling genes were established. The random forest algorithm was used for feature selection to identify BPTF, SIN3A and CNOT1 as characterized chromatin remodelers in ccRCC with good prognostic value. YY1 was indicated to be a transcription factor of genes highly related to BPTF, SIN3A and CNOT1. Functional annotations indicated that BPTF, SIN3A, CNOT1 and YY1 are all involved in the ubiquitin-mediated proteolysis process and that high expression of any of the five associated E3 ubiquitin ligases found in the pathway suggests a good prognosis. Protein network analysis indicated that BPTF has a targeted regulatory effect on YY1. Another independent dataset from International Cancer Genome Consortium (ICGC) showed a strong consistency with results in TCGA. In conclusion, we demonstrate that BPTF, SIN3A and CNOT1 are novel prognostic factors that predict good survival in ccRCC. We predicted that the good prognostic value of chromatin-remodeling genes BPTF and SIN3A is related to the regulation of YY1 and that YY1 regulates E3 ubiquitin ligases for further degradation of oncoproteins in ccRCC.

Perinatal exposure to bisphenol A (BPA) contributes to neurological disorders in offspring, but the underlying mechanisms are still poorly understood. The abnormal release of neuroactive metabolites in the tryptophan (TRP) and dopamine (DA) pathways is considered to be closely associated with some disorders. Thus, in this study, TRP and DA pathways in adult female mouse offspring were investigated when the pregnant mice were given either vehicle or BPA (2, 10, or 100 μg/kg/d) from day 6 of gestation until weaning. Then, the serum and brain samples of offspring were collected at 3, 6 and 9 months, and 12 neuroactive metabolites in the TRP and DA pathways were detected. The results showed that, in the TRP pathway, TRP levels decreased, whereas kynurenine (KYN) levels and TRP turnover increased in the brain. In the serum, TRP, KYN and 5-hydroxytryptamine (5-HT) levels decreased significantly. For the DA pathway, DA and DA metabolites, including 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT) and homovanillic acid (HVA), reduced significantly in the brain and serum. DA turnover decreased dramatically in the brain but enhanced in the serum. The disturbance of these two metabolic pathways might be one of the potential mechanisms of BPA-induced neuropsychiatric disorders.

Tryptophan (TRP) and dopamine (DA) pathways are of great importance for their related pathology and physiology. In the present study, a new reliable and sensitive analytical method was developed and validated for 12 neuroactive metabolites in TRP and DA pathways in mouse serum and brain by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UHPLC–MS/MS). The method exhibited good sensitivity as the lower limit of detections ranged from 0.10 to 0.50 ng/ml and the lower limit of quantifications ranged from 0.20 to 2.00 ng/ml by derivatization with dansyl chloride (DNS-Cl) following solid phase extraction (SPE) on C18 cartridges. Good linearity (R2 > 0.99), intra-day precision (

// Li Liu 1, * , Ying Xiong 1, * , Wei Xi 1, * , Jiajun Wang 1 , Yang Qu 1 , Zhiyuan Lin 1 , Xiang Chen 1 , Jiaxi Yao 1 , Jiejie Xu 2 , Jianming Guo 1 1 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai 200032, China 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China * These authors contributed equally to this work Correspondence to: Jiejie Xu, email: jjxufdu@fudan.edu.cn Jianming Guo, email: guo.jianming@zs-hospital.sh.cn Keywords: metastatic renal cell carcinoma, GALNT10, prognosis, biomarker, tyrosine kinase inhibitors Received: November 11, 2016 Accepted: January 11, 2017 Published: January 21, 2017 ABSTRACT Background and Purpose: A previous study demonstrated that GALNT10 affects the sensitivity of cancer cells to tyrosine kinase inhibitor (TKI) therapy. The aim of this study was to assess whether GALNT10 holds a prognostic role in metastatic renal cell carcinoma (mRCC) patients treated with TKI agents. Results: GALNT10 had no statistical correlation with any other clinicopathological parameters except for route of gaining samples ( P = 0.001) and Heng's risk stratification ( P = 0.011). Patients with high level of GALNT10 had significantly shorter overall survival (OS) ( P < 0.001) and progression-free survival (PFS) ( P = 0.002). Importantly, this relationship existed in OS and PFS analyses in sunitinib-treated patients and in OS analyses in sorafenib-treated patients ( P = 0.024). In contrast to sorafenib group, percentage of partial response (PR) and stable disease (SD) were higher in sunitinib group, while percentage of progression disease (PD) was much lower. Univariate and multivariate analyses identified that GALNT10 was an independent prognostic factor for OS (HR = 1.938, P = 0.014), not for PFS (HR = 1.532, P = 0.065), in mRCC. Incorporating it into Heng's risk model could sharpen its efficacy in distinguishing patients with potential higher risk. Materials and Methods: We retrospectively enrolled 138 mRCC patients treated with sunitinib or sorafenib at Zhongshan Hospital, Shanghai, China. A total of 111 valid cases were finally applied for analyses. Conclusions: These findings suggest that GALNT10 could be applied as a prognostic marker for OS in mRCC patients.

The aim of this study was to determine whether CD8A total of 231 mRCC patients, from 2007 to 2017, treated with sunitinib or sorafenib in Zhongshan Hospital, Fudan University were included in the study analyses. CD8, PD-1, and PD-L1 was assessed by immunohistochemistry on continuous paraffin-embedded slides. Kaplan-Meier method and COX regression model were applied in the survival analyses.Baseline characteristics were comparable between the training (n=118) and validation (n=113) sets. Patients with high CD8Our findings suggest that abundant CD8

A method for the identification and quantification of bisphenol A and 12 bisphenol analogues in river water and sediment samples combining liquid-liquid extraction, precolumn derivatization, and ultra high-performance liquid chromatography coupled with tandem mass spectrometry was developed and validated. Analytes were extracted from the river water sample using a liquid-liquid extraction method. Dansyl chloride was selected as a derivatization reagent. Derivatization reaction conditions affecting production of the dansyl derivatives were tested and optimized. All the derivatized target compounds were well separated and eluted in 10 min. Dansyl chloride labeled compounds were analyzed using a high-resolution mass spectrometer with electrospray ionization in the positive mode, and the results were confirmed and quantified in the parallel reaction monitoring mode. The method validation results showed a satisfactory level of sensitivity. Linearity was assessed using matrix-matched standard calibration, and good correlation coefficients were obtained. The limits of quantification for the analytes ranged from 0.005 to 0.02 ng/mL in river water and from 0.15 to 0.80 ng/g in sediment. Good reproducibility of the method in terms of intra- and interday precision was achieved, yielding relative standard deviations of less than 10.1 and 11.6%, respectively. Finally, this method was successfully applied to the analysis of real samples.

Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases.