Laparoscopic Ureteric Reconstruction After Partial Ureterectomy for Locally Advanced and Recurrent Pelvic Malignancies (with Video).

BACKGROUND: The urinary tract is one of the most frequently involved organs in advanced non-urologic pelvic malignances. Extensive resection of ureteric organs is mandatory during a curative surgery. Urinary reconstruction after partial ureterectomy, the most challenging situation, is associated with a higher incidence of complication than cystectomy, especially when performed with laparoscopy. Furthermore, to date, no generally accepted strategy for urinary reconstruction after extensive tumor resection with partial ureterectomy has been established. METHODS: The study identified and scrutinized intraoperative videos and clinical records of patients with locally advanced or recurrent pelvic malignancies who underwent segmental ureterectomy during en bloc resection of advanced tumors between February 2020 and February 2024. RESULTS: The study enrolled nine patients, including four cases managed by ureteroureteral anastomosis, two cases managed by ureteroneocystomy, two cases managed by Boari flap reconstruction, and one case managed by ileal interposition. In all nine cases, R0 margins were obtained, and no case needed conversion to laparotomy. No clinical evidence of postoperative urinary leakage was identified. The median follow-up period was 14 months (range, 5-19 months). In three of the nine cases, recurrence was identified, at the 3rd, 18th, and 19th month follow-up evaluations, respectively. One patient died of systemic metastasis. CONCLUSIONS: Laparoscopic ureteric reconstruction is feasible for patients who undergo segmental ureterectomy during extensive surgery for locally advanced or recurrent pelvic malignancies. A low anastomotic leakage rate and favorable postoperative renal function could be achieved in this study when anastomosis was performed laparoscopically.

Laparoscopic Pelvic Exenteration with Bladder Sparing for Men with Locally Advanced Rectal Cancer (with Video).

OBJECTIVE: The aim of this article was to introduce a fascial space priority approach for laparoscopic pelvic exenteration (PE) with bladder-sparing for men with locally advanced rectal cancer. METHODS: We present a video of bladder-sparing laparoscopic PE with fascial space priority approach in a 70-year old man. The systematic de-arterialization of the prostate on the basis of complete separation of the avascular lateral pelvic spaces is introduced in detail. RESULTS: The operation time was 360 min and the estimated intraoperative blood loss was 50 mL. The postoperative course was uneventful and the patient was discharged on postoperative day 14. Histopathological examination showed all margins to be tumor-free. CONCLUSIONS: Bladder-sparing laparoscopic PE using a fascial space priority approach is a feasible and safe procedure that can be performed in well-selected patients following neoadjuvant chemoradiotherapy. Extensive multivisceral resection is possible without a permanent stoma.

Fascial space priority approach for laparoscopic total pelvic exenteration in patients with locally advanced rectal cancer.

BACKGROUND: Total pelvic exenteration (TPE) with intent to achieve a pathological R0 resection is now considered as the only chance of a long-term survival for locally advanced rectal cancer (LARC) invading into adjacent organs. Lately, laparoscopic total pelvic exenteration (LTPE) is performed and achieved in several specialized centers and showed a promising application prospect. Although this is universally realized by surgeons, there are only few specialized centers to perform this complex surgery, due to concerns about the high morbidity and mortality. The techniques associated need to be disclosed and facilitated. OBJECTIVE: The aim of this article is to introduce a fascial space priority approach for laparoscopic TPE step by step (with video). METHODS: We describe here a fascial space priority approach for LTPE in highly selected patients with locally advanced rectal cancer. The main principle of this approach is that all of the pelvic organs are considered as a whole, the non-vascular spaces surrounding it are separated in the first place, the vascular pedicle and nerve pedicle of pelvic organs can be isolated and then transected precisely. Meanwhile, the associated key landmarks of this approach are disclosed (see the video). RESULTS: The ureterohypogastric nerve fascia (UHGNF) and the vesicohypogastric fascia (VHGF) are two vital embryological planes on the lateral compartment of pelvis. The spaces on either side of them together with the retrorectal space, the space of Retzius, are all non-vascular spaces, and dissection of these spaces in LTPE surgery can be achieved simply and practicably. The ureter, the umbilical artery, the arcus tendinous fasciae pelvis (ATFP), piriformis and the puboprostatic ligament (PPL) are all important landmarks during surgery. Step-by-step illustration with precise anatomical landmarks in the present video may lead to less intraoperative blood loss and complications. CONCLUSIONS: LTPE with fascial space priority approach might be a standard surgical procedure for total pelvic exenteration with clear anatomy and reduced blood loss.

Metastasis to lateral lymph nodes with no mesenteric lymph node involvement in low rectal cancer: a retrospective case series.

PURPOSE: The aim of this study is to examine the pattern of lymph node metastasis (lateral vs. mesenteric lymph nodes) in low rectal cancer. METHODS: This retrospective analysis included all patients undergoing laparoscopic total mesorectal excision plus lateral lymph node dissection for advanced low rectal cancer (up to 8 cm from the anal verge) during a period from July 1, 2017, to August 31, 2019, at the Department of Colorectal Surgery, Tianjin Union Medical Center. The decision to conduct lateral lymph node dissection was based on positive findings in preoperative imaging assessments. RESULTS: A total of 42 patients were included in data analysis. Surgery was successfully completed as planned, without conversion to open surgery in any case. A minimum of 10 mesenteric lymph nodes and 1 lateral lymph node on each side were dissected in all patients. Pathologic examination of resected specimens showed no metastasis to either mesenteric or lateral lymph nodes in 7 (16.7%) case, metastasis to both mesenteric and lateral lymph nodes in 26 (61.9%) cases, metastasis to mesenteric but not lateral lymph nodes in 4 (9.5%) cases, and metastasis to lateral but not mesenteric lymph nodes in 5 (11.9%) cases (n = 2 in the obturator region; n = 3 in the iliac artery region). CONCLUSION: A clinically significant proportion of low rectal cancer patients have metastasis to lateral lymph nodes without involvement of mesenteric lymph nodes. More carefully planned prospective studies are needed to verify this preliminary finding.

Inhibitory Effects of Resveratrol on the Human Alveolar Rhabdomyosarcoma Cell Line PLA-802 through Inhibition of the TGF-ß1/Smad Signaling Pathway.

While anti-tumor activity of resveratrol has been demonstrated for many cancers, little is known about its effects on soft tissue sarcoma. Overexpression of TGF-ß1, a protein inhibited by resveratrol, is a well-known feature of the rhabdomyosarcoma (RMS), a type of soft tissue sarcoma. In the present study, we examined the effects of resveratrol on the human alveolar RMS (ARMS) cell line PLA-802. Cultured PLA-802 cells were treated with different concentrations of resveratrol at distinct time points and changes in their growth, cell cycle progression and TGF-ß1 signaling were assessed. MTT assay showed a decrease in the viability of PLA-802 cells treated with resveratrol (p < 0.05). Cell cycle analysis using flow cytometry revealed that resveratrol induced a significant decrease in the number of cells in S phase and an increase in the number of cells in G1 phase (p < 0.05). Furthermore, expression of TGF-ß1 and its downstream factor Smad4 mRNA and protein, assessed by RT-PCR and Western blot, were inhibited by resveratrol in a concentration- and time-dependent manner. Immunofluorescent staining results confirmed these changes in expression and showed that co-localization of TGF-ß1 with Smad4 was gradually decreased by resveratrol. Together, our results suggest that resveratrol may inhibit cell proliferation and cell cycle progression in PLA-802 cells through inhibiting activity of the TGF-ß1 signaling pathway. Our findings highlight the therapeutic potential of resveratrol for suppressing the tumorigenicity of human ARMS.

Bencycloquidium bromide inhibits nasal hypersecretion in a rat model of allergic rhinitis.

OBJECT AND DESIGN: This study is aimed at exploring the effect of Bencycloquidium bromide (BCQB), a novel M1/M3 receptor antagonist, on mucus secretion in a murine model of allergic rhinitis (AR). MATERIALS AND METHODS: Sprague-Dawley rats were sensitized with ovalbumin to induce AR. After BCQB treatment, nasal symptoms were evaluated. Nasal lavage fluid was used to detect the protein level of cytokines and histamine by the method of enzyme-linked immunosorbent assay. The nasal mucosa of all animals was prepared for western blot, quantitative real-time polymerase chain reaction and histochemical analysis. RESULTS: BCQB could not only alleviate typical AR symptoms including rhinorrhea, nasal itching and sneezing, but also inhibit the overexpression of mucin 5AC at the level of protein and mRNA. The release of histamine, the mRNA and protein level of IL-6, IL-13 and TNF-α, and the nuclear translocation of NF-κB (p65 and p50) were inhibited by BCQB. In addition, histological studies showed BCQB dramatically inhibited ovalbumin-induced nasal lesions, eosinophil infiltration, aggregation of mast cells, globlet cell hyperplasia and metaplasia. CONCLUSIONS: BCQB attenuates mucus hypersecretion in AR, possibly involving in the NF-κB signaling pathway.

The indications for hepatectomy for multinodular hepatocellular carcinoma: experience from a single institution.

AIMS: This study was conducted in order to investigate the indications for hepatecomy for multinodular hepatocellular carcinoma (MNHCC) in single institution. METHODS: We retrospectively analyzed the medical records from 55 MNHCC patients, mainly with Child-Pugh A liver function, who underwent hepatectomy from January 2006 to December 2008. Both short- and long-term outcomes were analyzed. In addition, the prognostic significance of clinicopathological factors on overall survival (OS) was investigated by univariate analysis using the log-rank test. A Cox proportional hazards model was used in a subsequent multivariate analysis. RESULTS: The perioperative morbidity rate (grade II or higher) was 18.2% (n = 10), and the in-hospital mortality rate was 3.6%. The median OS was 23.9 months (range, 2.5-84 months), whereas the median disease-free survival was 8.75 months (range, 1-65 months). Independent prognostic risk factors of 5-year OS included the number of tumors >2 (p = 0.032) and gross morphology indicating multiple tumor nodules scattered throughout the liver (p = 0.009). CONCLUSIONS: The postoperative morbidity and mortality rates were acceptable. The number of tumors >2 and gross morphology indicating multiple tumor nodules scattered throughout the liver were independent prognostic risk factors for patients with MNHCC after hepatectomy. Patients with both of these features had a very poor prognosis and were not considered suitable for surgery.

Preformulation characterization and in vivo absorption in beagle dogs of JFD, a novel anti-obesity drug for oral delivery.

JFD (N-isoleucyl-4-methyl-1,1-cyclopropyl-1-(4-chlorine)phenyl-2-amylamine·HCl) is a novel investigational anti-obesity drug without obvious cardiotoxicity. The objective of this study was to characterize the key physicochemical properties of JFD, including solution-state characterization (ionization constant, partition coefficient, aqueous and pH-solubility profile), solid-state characterization (particle size, thermal analysis, crystallinity and hygroscopicity) and drug-excipient chemical compatibility. A supporting in vivo absorption study was also carried out in beagle dogs. JFD bulk powders are prismatic crystals with a low degree of crystallinity, particle sizes of which are within 2-10 µm. JFD is highly hygroscopic, easily deliquesces to an amorphous glass solid and changes subsequently to another crystal form under an elevated moisture/temperature condition. Similar physical instability was also observed in real-time CheqSol solubility assay. pK(a) (7.49 ± 0.01), log P (5.10 ± 0.02) and intrinsic solubility (S0) (1.75 µg/ml) at 37 °C of JFD were obtained using potentiometric titration method. Based on these solution-state properties, JFD was estimated to be classified as BCS II, thus its dissolution rate may be an absorption-limiting step. Moreover, JFD was more chemically compatible with dibasic calcium phosphate, mannitol, hypromellose and colloidal silicon dioxide than with lactose and magnesium stearate. Further, JFD exhibited an acceptable pharmacokinetic profiling in beagle dogs and the pharmacokinetic parameters T(max), C(max), AUC(0-t) and absolute bioavailability were 1.60 ± 0.81 h, 0.78 ± 0.47 µg/ml, 3.77 ± 1.85 µg·h/ml and 52.30 ± 19.39%, respectively. The preformulation characterization provides valuable information for further development of oral administration of JFD.

Bimodal voltage dependence of TRPA1: mutations of a key pore helix residue reveal strong intrinsic voltage-dependent inactivation.

Transient receptor potential A1 (TRPA1) is implicated in somatosensory processing and pathological pain sensation. Although not strictly voltage-gated, ionic currents of TRPA1 typically rectify outwardly, indicating channel activation at depolarized membrane potentials. However, some reports also showed TRPA1 inactivation at high positive potentials, implicating voltage-dependent inactivation. Here we report a conserved leucine residue, L906, in the putative pore helix, which strongly impacts the voltage dependency of TRPA1. Mutation of the leucine to cysteine (L906C) converted the channel from outward to inward rectification independent of divalent cations and irrespective to stimulation by allyl isothiocyanate. The mutant, but not the wild-type channel, displayed exclusively voltage-dependent inactivation at positive potentials. The L906C mutation also exhibited reduced sensitivity to inhibition by TRPA1 blockers, HC030031 and ruthenium red. Further mutagenesis of the leucine to all natural amino acids individually revealed that most substitutions at L906 (15/19) resulted in inward rectification, with exceptions of three amino acids that dramatically reduced channel activity and one, methionine, which mimicked the wild-type channel. Our data are plausibly explained by a bimodal gating model involving both voltage-dependent activation and inactivation of TRPA1. We propose that the key pore helix residue, L906, plays an essential role in responding to the voltage-dependent gating.

Microarray analysis points to LMNB1 and JUN as potential target genes for predicting metastasis promotion by etoposide in colorectal cancer.

Etoposide is a second-line chemotherapy agent widely used for metastatic colorectal cancer. However, we discovered that etoposide treatment induced greater motility potential in four colorectal cancer cell lines. Therefore, we used microarrays to test the mRNA of these cancer cell lines to investigate the mechanisms of etoposide promoting colorectal cancer metastasis. Differentially expressed genes (DEGs) were identified by comparing the gene expression profiles in samples from etoposide-treated cells and untreated cells in all four colorectal cancer cell lines. Next, these genes went through the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway analysis. Among the top 10 genes including the upregulated and downregulated, eight genes had close interaction according to the STRING database: FAS, HMMR, JUN, LMNB1, MLL3, PLK2, STAG1 and TBL1X. After etoposide treatment, the cell cycle, metabolism-related and senescence signaling pathways in the colorectal cancer cell lines were significantly downregulated, whereas necroptosis and oncogene pathways were significantly upregulated. We suggest that the differentially expressed genes LMNB1 and JUN are potential targets for predicting colorectal cancer metastasis. These results provide clinical guidance in chemotherapy, and offer direction for further research in the mechanism of colorectal cancer metastasis.

A radiomics model based on T2WI and clinical indexes for prediction of lateral lymph node metastasis in rectal cancer.

OBJECTIVE: The aim of this study was to explore the clinical value of a radiomics prediction model based on T2-weighted imaging (T2WI) and clinical indexes in predicting lateral lymph node (LLN) metastasis in rectal cancer patients. METHODS: This was a retrospective analysis of 106 rectal cancer patients who had undergone LLN dissection. The clinical risk factors for LLN metastasis were selected by multivariable logistic regression analysis of the clinical indicators of the patients. The LLN radiomics features were extracted from the pelvic T2WI of the patients. The least absolute shrinkage and selection operator algorithm and backward stepwise regression method were adopted for feature selection. Three LLN metastasis prediction models were established through logistic regression analysis based on the clinical risk factors and radiomics features. Model performance was assessed in terms of discriminability and decision curve analysis in the training, verification and test sets. RESULTS: The model based on the combined T2WI radiomics features and clinical risk factors demonstrated the highest accuracy, surpassing the models based solely on either T2WI radiomics features or clinical risk factors. Specifically, the model achieved an AUC value of 0.836 in the test set. Decision curve analysis revealed that this model had the greatest clinical utility for the vast majority of the threshold probability range from 0.4 to 1.0. CONCLUSION: Combining T2WI radiomics features with clinical risk factors holds promise for the noninvasive assessment of the biological characteristics of the LLNs in rectal cancer, potentially aiding in therapeutic decision-making and optimizing patient outcomes.

Early-stage voiding function following uni- versus bilateral inferior vesical vessel resection during therapeutic lateral lymph node dissection with autonomic nerve sparing for advanced low rectal cancer (with video).

Introduction: Lateral lymph node dissection (LLND) has now been widely accepted as the optimal procedure to minimize lateral local recurrence (LLR) for selected cases with advanced lower rectal cancer in Asian countries. However, there is still controversy over the preservation or resection of the inferior vesical vessels (IVVs) during LLND due to concerns of impaired post-operative urinary function. Moreover, the standardized procedure for autonomic nerve preservation has not yet been established. Aim: To evaluate the early-stage postoperative voiding function in patients who underwent LLND with uni- versus bilateral resection of the IVVs and to introduce an autonomic nerve sparing technique with a fascial space priority approach (FSPA). Material and methods: LLND was performed in 106 consecutive patients with advanced low rectal cancer at Tianjin Union Medical Center from May 2017 to October 2022. Prospectively collected clinical data were retrospectively compared between patients who received uni-lateral and bilateral LLND. A video with narration was provided to introduce the stepwise procedure of autonomic nerve preservation during IVV resection. Results: The unilateral lymph node dissection (LND) group and the bilateral LND group included 75 and 31 cases, respectively. All LLNDs were performed with FSPA with IVV resection as a standard procedure. No significant differences were observed in overall catheterization days (p = 0.336) and re-catheterization rate (p = 0.575) between groups. No patients in either group suffered from long-term (≥ 30 days) voiding dysfunction. Conclusions: Autonomic nerve sparing is achievable with resection of IVVs during LLND. Satisfactory early-stage voiding function could be obtained with IVV resection on both sides.

Prediction of lateral lymph node metastasis in rectal cancer patients based on MRI using clinical, deep transfer learning, radiomic, and fusion models.

Introduction: Lateral lymph node (LLN) metastasis in rectal cancer significantly affects patient treatment and prognosis. This study aimed to comprehensively compare the performance of various predictive models in predicting LLN metastasis. Methods: In this retrospective study, data from 152 rectal cancer patients who underwent lateral lymph node (LLN) dissection were collected. The cohort was divided into a training set (n=86) from Tianjin Union Medical Center (TUMC), and two testing cohorts: testing cohort (TUMC) (n=37) and testing cohort from Gansu Provincial Hospital (GSPH) (n=29). A clinical model was established using clinical data; deep transfer learning models and radiomics models were developed using MRI images of the primary tumor (PT) and largest short-axis LLN (LLLN), visible LLN (VLLN) areas, along with a fusion model that integrates features from both deep transfer learning and radiomics. The diagnostic value of these models for LLN metastasis was analyzed based on postoperative LLN pathology. Results: Models based on LLLN image information generally outperformed those based on PT image information. Rradiomics models based on LLLN demonstrated improved robustness on external testing cohorts compared to those based on VLLN. Specifically, the radiomics model based on LLLN imaging achieved an AUC of 0.741 in the testing cohort (TUMC) and 0.713 in the testing cohort (GSPH) with the extra trees algorithm. Conclusion: Data from LLLN is a more reliable basis for predicting LLN metastasis in rectal cancer patients with suspicious LLN metastasis than data from PT. Among models performing adequately on the internal test set, all showed declines on the external test set, with LLLN_Rad_Models being less affected by scanning parameters and data sources.

The anti-inflammatory effect of kaempferol on early atherosclerosis in high cholesterol fed rabbits.

BACKGROUND: Atherosclerosis has been widely accepted as an inflammatory disease of vascular, adhesion molecules play an important role in the early progression of it. The aim of the present study was to evaluate the effect of kaempferol on the inflammatory molecules such as E-selectin (E-sel), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesionmolecule-1 (VCAM-1) and monocyte chemotactic protein-1 (MCP-1) in high cholesterol induced atherosclerosis rabbit models. METHODS: Thirty male New Zealand white (NZW) rabbits were randomly divided into five groups, control group, model group, fenofibrate (12 mg/kg) group and kaempferol groups (150 mg/kg and 30 mg/kg). The rabbits were fed with a normal diet or a high cholesterol diet for 10 weeks. Levels of blood lipids, serum tumour-necrosis factor-alpha (TNF-α) and serum interleukin-1beta (IL-1ß) were detected at the end of the sixth and tenth week. Malonaldehyde (MDA) level and superoxide dismutase (SOD) activity in serum were also determined. Lesion areas of the aorta were measured with morphometry analysis after ten weeks. Gene expression of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas was determined by RT-PCR (reverse transcription-polymerase chain reaction). Immunohistochemical staining was employed to measure protein expression of E-sel, ICAM-1, VCAM-1 and MCP-1. RESULTS: Model rabbits fed with ten weeks of high-cholesterol diet developed significant progression of atherosclerosis. Compared with the control, levels of blood lipids, TNF-α, IL-1ß and MDA increased markedly in serum of model rabbits, while SOD levels decreased. Gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in atherosclerotic aortas increased remarkably in model group. However, comparing to the model rabbits, levels of TNF-α, IL-1ß and MDA decreased significantly and serum SOD activity increased, gene and protein expressions of E-sel, ICAM-1, VCAM-1 and MCP-1 in aortas decreased significantly with the treatment of kaempferol. CONCLUSION: Kaempferol shows anti-atherosclerotic effect by modulating the gene and protein expression of inflammatory molecules.

The consequences of laparoscopic fascial space priority approach to lateral lymph node dissection on urinary and sexual functionality.

Introduction: In this prospective observational study, we aimed to evaluate the consequences of laparoscopic fascia space priority lymph node dissection on urination and sexual function. Aim: To assess the consequences of laparoscopic lateral lymph node dissection (LLND) using the fascial space priority approach on urinary and sexual function in patients with advanced middle and low rectal cancer. Material and methods: Consecutive patients undergoing laparoscopic LLND using the fascial space priority approach from December 2020 to November 2022 were identified from Tianjin Union Medical Center. Clinical data including patient characteristics, surgical details, and pathology were analysed. The urinary function was assessed by international prostate symptom score (IPSS) questionnaire and residual urine volume. The sexual function was investigated using the international index of erectile function (IIEF) questionnaire. Results: A total of 51 patients, mean age 60.5 ±10.9 years, were identified. The lymph nodes were positive in 70.6% (36/51) of the patients. There was no significant difference between the preoperative IPSS score and that at 6 months (5.2 ±2.1 vs. 5.6 ±1.5; p = 0.16). And there was no significant difference between the residual urine volume and that at 6 months (9.5 ±10.6 vs. 8.6 ±6.3; p = 0.61). The IIEF score before the surgery showed no significant difference from that at 6 months after the surgery (21.1 ±2.2 vs. 20.6 ±2.3; p = 0.26). Conclusions: Laparoscopic LLND using a fascial space priority approach can effectively protect the autonomic nerves. The procedure reduces short-term urination and sexual function, but it has little effect on long-term function.

An Analysis of the Gene Expression Associated with Lymph Node Metastasis in Colorectal Cancer.

Objective: This study aimed to explore the genes regulating lymph node metastasis in colorectal cancer (CRC) and to clarify their relationship with tumor immune cell infiltration and patient prognoses. Methods: The data sets of CRC patients were collected through the Cancer Gene Atlas database; the differentially expressed genes (DEGs) associated with CRC lymph node metastasis were screened; a protein-protein interaction (PPI) network was constructed; the top 20 hub genes were selected; the Gene Ontology functions and the Kyoto Encyclopedia of Genes and Genomes pathways were enriched and analyzed. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to further screen the characteristic genes associated with CRC lymph node metastasis in 20 hub genes, exploring the correlation between the characteristic genes and immune cell infiltration, conducting a univariate COX analysis on the characteristic genes, obtaining survival-related genes, constructing a risk score formula, conducting a Kaplan-Meier analysis based on the risk score formula, and performing a multivariate COX regression analysis on the clinical factors and risk scores. Results: A total of 62 DEGs associated with CRC lymph node metastasis were obtained. Among the 20 hub genes identified via PPI, only calcium-activated chloride channel regulator 1 (CLCA1) expression was down-regulated in lymph node metastasis, and the rest were up-regulated. A total of nine characteristic genes associated with CRC lymph node metastasis (KIF1A, TMEM59L, CLCA1, COL9A3, GDF5, TUBB2B, STMN2, FOXN1, and SCN5A) were screened using the LASSO regression method. The nine characteristic genes were significantly related to different kinds of immune cell infiltration, from which three survival-related genes (TMEM59L, CLCA1, and TUBB2B) were screened. A multi-factor COX regression showed that the risk scores obtained from TMEM59L, CLCA1, and TUBB2B were independent prognostic factors. Immunohistochemical validation was performed in tissue samples from patients with rectal and colon cancer. Conclusion: TMEM59L, CLCA1, and TUBB2B were independent prognostic factors associated with lymphatic metastasis of CRC.

Network Pharmacology-Based Analysis of the Potential Biological Mechanisms of Coix Seed against Colorectal Cancer.

Objective: The aim of this study was to explore the potential biological mechanisms of coix seed in the treatment of colorectal cancer (CRC) based on network pharmacology analysis. Methods: The active components of coix seed and their potential action targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP). The disease targets related to CRC were obtained from the DisGeNET database. The intersection targets of the drug targets and disease targets were selected, and a component-target-disease network was built using Cytoscape 3.8.0 tool. A global network of the core target protein interactions was constructed using String database. Biological function analysis and pathway enrichment analysis of core targets were conducted to explore the potential. Results: A total of nine active components were obtained from the TCMSP database corresponding to 37 targets. Further analysis showed that 18 overlapping targets were associated with CRC. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted based on the 18 targets and 11 significantly enriched signaling pathways implicated in CRC were identified. Conclusion: The multicomponent and multitarget characteristics of coix seed are preliminarily verified, and the potential biological mechanisms of coix seed in the treatment of CRC are predicted, which provides a theoretical basis for the experimental research.

Subchronic toxicity and toxicokinetics of long-term intranasal administration of bencycloquidium bromide: a 91-day study in dogs.

The subchronic toxicity and toxicokinetics of Bencycloquidium bromide (BCQB) were evaluated after 91-day intranasal administration in dogs at daily dose levels of 2.5, 5.0, and 10.0 mg/kg. Following repeated exposure to medium- or high-dose of BCQB, apparent changes were observed in the levels of blood glucose, creatinine or blood urea nitrogen in both male and female dogs. The no-observed-adverse-effect level (NOAEL) of BCQB was considered to be 2.5 mg/kg/day under the present study conditions. There were no significant gender differences in most indexes of subchronic toxicity throughout the experimental period with the exception of food consumption and body weight, or in the parameters of plasma toxicokinetics after either single-dose or repeated administrations of BCQB at each dosage. In dog, BCQB did not accumulate in blood plasma, while much higher concentrations of BCQB residues were found in most tissues examined (especially the kidney) following 91-day repeated exposure relative to a single dose. In all tissues except the reproductive organs, BCQB concentrations reverted to low levels by 2 weeks post-dosing. The results indicate that blood glucose levels and renal function should be closely monitored when BCQB is used in long-term therapy.

[Study on pharmacokinetics and absolute bioavailability of sinomenine in beagle dogs].

OBJECTIVE: To study pharmacokinetic parameters and absolute bioavailability for oral use of sinomenine tablet in beagle dogs. METHOD: Applying to double cycle self crossover design, a single oral or intravenous dose of 10 mg x kg(-1) sinomenine was given to 10 beagle dogs. Drug concentrations in plasma were determined by HPLC. The pharmacokinetic parameters were calculated by 3P97 pharmacokinetic program. RESULT: The concentration-time curves of oral administration fitted to one compartment model in the beagle dogs. The T(max), C(max), t1/2 and AUC(0-T) was (82.5 +/- 13.9) min, (0.15 +/- 0.027) mg x L(-1), (87.6 +/- 28.3) min and (28.43 +/- 3.48) mg x min x L(-1), respectively. The concentration -time curves of i.v. fitted to two compartment model in the beagle dogs. The t1/2beta and AUC(0-T) was (106.7 +/- 120.2) min and (93.32 +/- 82.08) mg x min x L(-1). The absolute bioavailability for oral use was (30.46 +/- 4.24)%. CONCLUSION: The absolute bioavailability of sinomenine is low, and the elimination of sinomenine tablet is fast.