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A one‐pot method has been developed for synthesizing diverse substituted 5‐aminotetrazoles via the electrochemically induced desulfurizative addition–cyclization of thioureas with azidotrimethylsilane. This methodology enables the construction of C−N and N−N bonds under mild reaction conditions without transition metal catalysts or external oxidizing agents. The applicability of this approach is demonstrated by its broad substrate scope, compatibility with various functional groups, scalability to gram‐scale synthesis, and practicality evidenced by the synthesis of an antibacterial agent. [ABSTRACT FROM AUTHOR]

Transition‐mental‐free multi‐component hydroxysulfenylation of styrenes with NH4SCN and water to from β‐hydroxysulfides is established. The reaction mechanism proceeded via a domino reaction after a radical addition to 2‐phenylimidazo[1,2‐a]pyridines. This approach features a wide substrate scope and functional group compatibility, providing 34 compounds in acceptable yields. [ABSTRACT FROM AUTHOR]

A multicomponent tandem arylation reaction was established under transition‐metal‐free conditions to synthesize structurally diverse imidazo[1,2‐a]pyridines. As N,N‐dimethylaniline is not only a reactant but also a methylation reagent, its use affords an alternative route for methylation. This approach features mild reaction conditions and good functional group tolerance, providing 29 compounds in acceptable yields. [ABSTRACT FROM AUTHOR]

Herein, we report a one-pot tandem reaction for the synthesis of 1,4-benzoxazine derivatives with up to 83% yield. The present protocol, using ethanol as a solvent and avoiding the use of transition metal catalysts, exhibits a wide range of substrate scope and functional group tolerance. This novel, mild and efficient method is highly promising for constructing 1,4-benzoxazine derivatives. [ABSTRACT FROM AUTHOR]

Herein we report an annulation of phenylhydrazone via a tandem nitrification, reduction, cyclization protocol employing cobalt nitrate and 1,2‐dichloroethane to produce substituted 1H‐1,2,4‐triazoles. Notably, 1,2‐dichloroethane serves both the solvent and a hydrogen source for transfer hydrogenation. This methodology works under mild conditions, providing a direct approach for the synthesis of 1H‐1,2,4‐triazoles. [ABSTRACT FROM AUTHOR]

Purpose: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. Methods: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. Results: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93–1.00) and 95.5% (95% CI, 0.91–1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74–0.97) vs 4.2% (95% CI, 0.92–1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82–1.00) vs 12.6% (95% CI, 0.81–0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64–0.92) vs 84.7% (95% CI, 0.78–0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). Conclusion: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised. [ABSTRACT FROM AUTHOR]

Purpose: Local excision is an effective approach for managing rectal cancer exhibiting substantial regression after neoadjuvant chemoradiotherapy. The purpose of this study is to compare the outcomes between local excision and total mesorectal excision in rectal cancer patients achieving clinical complete or near-complete response after neoadjuvant chemoradiotherapy. Methods: This is a retrospective cohort study that includes a consecutive series of rectal cancer patients who responded well to neoadjuvant chemoradiotherapy followed by surgery. A total of 180 rectal cancer patients at a single institution during a 12-year period are included. The main outcomes include short-term outcomes, oncological outcomes, and functional outcomes between the two groups. Results: A total of 180 patients were included in the study. Sixty-one (33.9%) received local excision and 119 (66.1%) received total mesorectal excision. The baseline characteristics were generally balanced between the two groups. The local excision group demonstrated a significantly shorter operative time, less blood loss, and shorter hospital stay (p < 0.001). 3-year overall survival rates were 97.5% (95% CI, 0.93–1.00) and 95.5% (95% CI, 0.91–1.00) between the two groups (p = 0.38). The local excision group exhibited significantly higher 3-year local recurrence rates 15.7% (95% CI, 0.74–0.97) vs 4.2% (95% CI, 0.92–1.00) (p = 0.017), yet lower 3-year distant metastasis rates 9.6% (95% CI, 0.82–1.00) vs 12.6% (95% CI, 0.81–0.94) (p = 0.33) and lower 3-year disease-free survival rates 76.8% (95% CI, 0.64–0.92) vs 84.7% (95% CI, 0.78–0.92) (p = 0.56) comparing with the total mesorectal excision group. The local excision group demonstrated significantly better functional outcomes compared with the total mesorectal excision group (p < 0.001). Conclusion: Patients who achieve either clinical complete or near-complete response after neoadjuvant chemoradiotherapy are suitable candidates for local excision. The local excision group demonstrated superior short-term and functional outcomes, and the oncological outcomes were not compromised. [ABSTRACT FROM AUTHOR]

Herein, we present a strategy for the synthesis of pyrrole alkaloid derivatives through a tandem C−N, C−C coupling reaction employing 2‐pyrrole formaldehyde and proline as starting materials. This cyclization protocol is successfully applied to polarity‐controlled site‐selective and stereoselective C(sp3)−H hydrocarboxylation of proline derivatives, allowing for a remarkably streamlined synthesis of pyrrole alkaloid derivatives which have shown promising biological activities. [ABSTRACT FROM AUTHOR]

Although surgical resection combined with neoadjuvant radiation therapy can reduce the local recurrence rate of rectal cancer, not all patients benefit from neoadjuvant radiation therapy. Therefore, screening for patients with rectal cancer who are sensitive or resistant to radiation therapy has great clinical significance. Patients with rectal cancer were selected according to postoperative tumor regression grade, and tumor samples were taken for detection. Differential genes between radiation-resistant and radiation-sensitive tissues were screened and validated by Illumina Infinium MethylationEPIC BeadChip, proteomics, Agena MassARRAY methylation, reverse transcription quantitative real-time polymerase chain reaction, and immunohistochemistry. In vitro and in vivo functional experiments verified the role of DSTN. Protein coimmunoprecipitation, western blot, and immunofluorescence were used to investigate the mechanisms of DSTN -related radiation resistance. DSTN was found to be highly expressed (P <.05) and hypomethylated (P <.01) in rectal cancer tissues resistant to neoadjuvant radiation therapy. Follow-up data confirmed that patients with high expression of DSTN in neoadjuvant radiation therapy–resistant rectal cancer tissues had shorter disease-free survival (P <.05). DSTN expression increased after methyltransferase inhibitor inhibition of DNA methylation in colorectal cancer cells (P <.05). In vitro and in vivo experiments showed that knockdown of DSTN promoted the sensitivity of colorectal cancer cells to radiation therapy, and overexpression of DSTN promoted the resistance of colorectal cancer cells to radiation (P <.05). The Wnt/β-catenin signaling pathway was activated in colorectal cancer cells overexpressing DSTN. β-catenin was highly expressed in radiation therapy–resistant tissues, and there was a linear correlation between the expression of DSTN and β-catenin (P <.0001). Further studies showed that DSTN can bind to β-catenin and increase its stability. The degree of DNA methylation and the expression level of DSTN can be used as biomarkers to predict the sensitivity of neoadjuvant radiation therapy for rectal cancer. DSTN and β-catenin are also expected to become a reference for the selection of neoadjuvant radiation therapy. [ABSTRACT FROM AUTHOR]

Metastasis is the main cause of mortality in colorectal cancer (CRC) patients. Exploring the mechanisms of metastasis is of great importance in both clinical and fundamental CRC research. CRC is a highly heterogeneous disease with variable therapeutic outcomes of treatment. In this study, we applied spatial transcriptomics (ST) to generate a tissue-wide transcriptome from two primary colorectal cancer tissues and their matched liver metastatic tissues. Spatial RNA information showed intratumoral heterogeneity (ITH) of both primary and metastatic tissues. The comparison of gene expressions across tissues revealed an apparent enrichment of cancer stem cells (CSCs) in metastatic tissues and identified FOXD1 as a novel metastatic CSC marker. Trajectory and pseudo-time analyses revealed distinct evolutionary trajectories and a dedifferentiation-differentiation process during metastasis. CellphoneDB analysis suggested a dominant interaction of CD74-MIF with tumor cells in metastatic tissues. Further analysis confirmed FOXD1 as a maker of CSCs and the predictor of patient survival, especially in metastatic diseases. Our study found ITH of primary and metastatic tissues and provides novel insights into the cellular mechanisms underlying liver metastasis of CRC and foundations for therapeutic strategies for CRC metastasis. In this study, we applied spatial transcriptomics (ST) to generate a tissue-wide transcriptome from two primary colorectal cancer tissues and their matched liver metastatic tissues. Spatial RNA information showed intratumoral heterogeneity (ITH) of both primary and metastatic tissues. • The comparison of gene expressions across tissues revealed an apparent enrichment of cancer stem cells (CSCs) in metastatic tissues and identified FOXD1 as a novel metastatic CSC marker. • CellphoneDB analysis suggested a dominant interaction of CD74-MIF with tumor cells in metastatic tissues. • Further analysis confirmed FOXD1 as a maker of CSCs and the predictor of patient survival, especially in metastatic diseases. • Our study found ITH of primary and metastatic tissues and provides novel insights into the cellular mechanisms underlying liver metastasis of CRC and foundations for therapeutic strategies for CRC metastasis. [ABSTRACT FROM AUTHOR]

Background: The safe distance between the intraoperative resection line and the visible margin of the distal rectal tumor after preoperative radiotherapy is unclear. We aimed to investigate the furthest tumor intramural spread distance in fresh tissue to determine a safe distal intraoperative resection margin length. Methods: Twenty rectal cancer specimens were collected after preoperative radiotherapy. Tumor intramural spread distances were defined as the distance between the tumor's visible and microscopic margins. Visible tumor margins in fresh specimens were identified during the operation and were labeled with 5 - 0 sutures under the naked eye at the distal 5, 6, and 7 o'clock directions of visible margins immediately after removal of the tumor. After fixation with formalin, the sutures were injected with nanocarbon particles. Longitudinal tissues were collected along three labels and stained with hematoxylin and eosin. The spread distance after formalin fixation was measured between the furthest intramural spread of tumor cells and the nanocarbon under a microscope. A positive intramural spread distance indicated that the furthest tumor cell was distal to the nanocarbon, and a negative value indicated that the tumor cell was proximal to the nanocarbon. The tumor intramural spread distance in fresh tissue during the operation was 1.75 times the tumor intramural spread distance after formalin fixation according to the literature. Results: At the distal 5, 6, and 7 o'clock direction, seven (35%), five (25%), and six (30%) patients, respectively, had distal tumor cell intramural spread distance > 0 mm. The mean and 95% confidence interval of tumor cell intramural spread distance in fresh tissue during operation was − 0.3 (95%CI − 4.0 ~ 3.4) mm, − 0.9 (95%CI − 3.4 ~ 1.7) mm, and − 0.4 (95%CI − 3.5 ~ 2.8) mm, respectively. The maximal intraoperative intramural spread distances in fresh tissue were 8.8, 7, and 7 mm, respectively. Conclusions: The intraoperative distance between the distal resection line and the visible margin of the rectal tumor after radiotherapy should not be less than 1 cm to ensure oncological safety. [ABSTRACT FROM AUTHOR]

Background: Early detection of colorectal carcinoma (CRC) would help to identify tumors when curative treatments are available and beneficial. However, current screening methods for CRC, e.g., colonoscopy, may affect patients' compliance due to the uncomfortable, invasive and time-consuming process. In recent decades, methylation profiles of blood-based circulating tumor DNA (ctDNA) have shown promising results in the early detection of multiple tumors. Here we conducted a study to investigate the performance of ctDNA methylation markers in early detection of CRC. Results: In total, 742 participants were enrolled in the study including CRC (n = 332), healthy control (n = 333), benign colorectal disease (n = 65) and advanced adenoma (n = 12). After age-matched and randomization, 298 participants (149 cancer and 149 healthy control) were included in training set and 141 (67 cancer and 74 healthy control) were in test set. In the training set, the specificity was 89.3% (83.2–93.7%) and the sensitivity was 88.6% (82.4–93.2%). In terms of different stages, the sensitivities were 79.4% (62.1–91.2%) in patients with stage I, 88.9% (77.3–95.8%) in patients with stage II, 91.4% (76.9–98.2%) in patients with stage III and 96.2% (80.3–99.9%) in patients with stage IV. Similar results were validated in the test set with the specificity of 91.9% (83.1–97.0%) and sensitivity of 83.6% (72.5–91.6%). Sensitivities for stage I-III were 87.0% (79.7–92.4%) in the training set and 82.5% (70.2–91.3%) in the test set, respectively. In the unmatched total population, the positive ratios were 7.8% (5.2–11.2%) in healthy control, 30.8% (19.9–43.5%) in benign colorectal disease and 58.3% (27.5–84.7%) in advanced adenoma, while the sensitivities of stage I–IV were similar with training and test sets. Compared with methylated SEPT9 model, the present model had higher sensitivity (87.0% [81.8–91.2%] versus 41.2% [34.6–48.1%], P < 0.001) under comparable specificity (90.1% [85.4–93.7%] versus 90.6% [86.0–94.1%]). Conclusions: Together our findings showed that ctDNA methylation markers were promising in the early detection of CRC. Further validation of this model is warranted in prospective studies. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to evaluate the risk factors for anastomotic leakage (AL) after anterior resection for middle and low rectal cancer in order to help surgeons to decide which patients could benefit from a diverting stoma. Methods: Data on 319 patients having a middle and low rectal cancer resection with anastomosis between May 2011 and October 2015 from two hospitals were included in the study. The analysis included the following variables: patient-related variables (gender, age, diabetes mellitus, ASA score, preoperative radiochemotherapy, body mass index, blood hemoglobin, and serum albumin level), tumor-related variables (K-ras status, distance of tumor from the anal verge, histopathologic grade, pathological T stage, pathological N stage, pathological M stage, TNM stage, and tumor size), and surgery-related variables (laparoscopic or open surgery, blood loss, and operative time). Univariate and multivariate regression analysis were carried out to identify risk factors for AL. Results: The AL rate was 11.91% (38/319). Male (OR 2.898, 95% CI 1.265-6.637, p = 0.012), diabetes mellitus (OR 2.482, 95% CI 1.004-6.134, p = 0.049), K-ras mutation (OR 2.544, 95% CI 1.210-5.348, p = 0.014), distance of tumor from the anal verge (OR 3.445, 95% CI 1.631-7.279, p = 0.001), and preoperative radiochemotherapy (OR 2.790, 95% CI 1.056-7.372, p = 0.039) were independent risk factors of AL. One (2.63%) in 38 patients with AL presented with no risk factor of AL, 6 (15.8%) in 38 patients with 1 risk factor, 16 (42.1%) in 38 patients with 2 risk factors, 9 (23.7%) in 38 patients with 3 risk factors, and 6 (15.7%) in 38 patients with 4 risk factors. No patient with 5 risk factors in our study. AL rate increased with the elevated number of risk factors clustering in individuals. Conclusions: K-ras mutation is first reported to be an independent risk factor for AL after sphincter-preserving surgery without diverting stoma. A diverting stoma should be performed in sphincter-preserving surgery for middle and low rectal cancer patients with 2 or more risk factors identified in this analysis. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemoradiotherapy (nCRT) in addition to the curative surgery has been the first of treatment for local advanced rectal cancer because of its benefits in local recurrence and sphincter-saving. However, its side effects on anorectal function have been recognized. The histopathological changes on internal anal sphincter (IAS) have been reported, but ultrastructure changes of external anal sphincter (EAS) are unknown. The aim of this study is to detect the alterations on the gross morphology of IAS and ultrastructure of EAS after nCRT. Methods: We collected 34 anal canal specimens of patients undergoing abdominoperineal resection (APR) prospectively. The length and thickness of IAS were measured with vernier caliper. The EAS was dissected for observation with transmission electron microscope (TEM). Results: Ten patients received nCRT (nCRT group) before surgery and 24 underwent APR directly (control group). The length and thickness of IAS in nCRT group were 22.68 ± 3.56 and 5.39 ± 0.74 mm, respectively. These parameters were 21.28 ± 3.62 and 5.35 ± 1.12 mm in control group, respectively. There were no significant differences in the length and thickness of IAS between the two groups ( P>0.05). In nCRT group, the sarcomere and myofibril were arranged disorderly and parts of them that were filled with collagenous fiber, triads, and mitochondria were destroyed severely and the glycogenosome also distributed disorderly. Such alterations of EAS did not occur in control group. Conclusions: The nCRT cannot change the gross morphology of IAS, while it induces serious damages to the ultrastructures of EAS which may adversely affect the anorectal function. [ABSTRACT FROM AUTHOR]

Background: Colonoscopic perforation (CP) has a low incidence rate. However, with the extensive use of colonoscopy, even low incidence rates should be evaluated to identify and address risks. Information on CP is quite limited in China. Objective: Our study aimed to determine the frequency of CP in colonoscopies performed by surgeons at a large teaching hospital in China over a 12-year period. Methods: A retrospective review of medical records was performed for all patients who had CPs from 1 January 2000 to 31 December 2012. Iatrogenic perforations were identified mainly by abdominal X-ray or computed tomography scan. Follow-up information of adverse events post-colonoscopy was identified from the colorectal surgery database of our hospital. Patients' demographic data, colonoscopy procedure information, location of perforation, treatment, and outcome were recorded. Results: A total of 110,785 diagnostic and therapeutic colonoscopy procedures were performed (86,800 diagnostic cases and 23,985 therapeutic cases) within the 12-year study period. A total of 14 incidents (0.012 %) of CP were reported (seven males and seven females), of which nine cases occurred during diagnostic colonoscopy (0.01 %) and five after therapeutic colonoscopy (three polypectomy cases, one endoscopic mucosal resection, and one endoscopic mucosal dissection). Mean patient age was 67.14 years. One case of CP (7.14 %) after colonoscopy polypectomy was treated using curative colonoscopy endoclips. Other patients underwent operations: six cases (46.15 %) of primary repair, four cases (28.57 %) of resection with anastomosis, and two cases (15.38 %) of resection without anastomosis. No obvious perforation was found in one patient (7.69 %). Surgeons attempted to treat one case laparoscopically but eventually resorted to open surgery. The postoperative course was uncomplicated in eight cases (57.14 %) and complicated in six cases (42.86 %) but without mortality. Conclusion: CP is a serious but rare complication of colonoscopy. A perforation risk of 0.012 % was found in our study. The optimal management of CP remains controversial. Treatment for CP should be individualized according to the patient's condition, related devices, and surgical skills of endoscopists or surgeons. Selective measures such as colonoscopy without intravenous sedation and decrease of loop formation can effectively reduce rates of perforation. [ABSTRACT FROM AUTHOR]