Clinical performance of the TrueMark™ MSI assay for microsatellite instability detection in a Chinese colorectal cancer cohort.

BACKGROUND: Microsatellite instability (MSI) and mismatch repair (MMR) detection is valuable in assessing prognosis and treatment options. However, the conventional detection methods such as immunohistochemistry (IHC) are limited by not fully consistent results as well as a long turnaround time. TrueMark™ MSI Assay is a novel solution for MSI analysis, but lack of research support in the Chinese colorectal cancer (CRC) patients. MATERIALS AND METHODS: 60 dMMR and 60 pMMR CRC samples identified by IHC were collected and their MSI status were detected using TrueMark™ MSI assay with an expanded panel of 13 markers. The overall performance and diagnostic concordance between TrueMark™ MSI test and MMR IHC analysis were assessed and analyzed. RESULTS: According to the TrueMark™ test, 55 out of the 120 (45.8 %) CRCs were identified as MSI-high (MSI-H) with an instability at ≥ 4/13 markers. Compared with the MMR IHC analysis, an overall percent agreement of 94.2 % and a Kappa of 0.883 were achieved. For the seven inconsistent samples, tumor mutation burden analysis was performed and the results supported the diagnosis by TrueMark™ test. To confirm the robustness of the above findings, a validation was performed in an independent cohort comprising 51 consecutive CRCs. Furthermore, an optimized panel composed of NR-21, NR-24, NR-27, ABI-16, ABI-17 and ABI-20B was developed by multivariate logistic regression model, and showed 100 % agreement with the 13-marker panel for MSI detection in both the derivation and validation sets. CONCLUSION: TrueMark™ MSI provides a fast, reliable and highly automated solution to MSI detection in Chinese CRC patients, and the new 6-marker panel we established shows promise deserving further evaluation.

Exploring the Effects of Online Physician Voice Pitch Range and Filled Pauses on Patient Satisfaction in Mobile Health Communication.

The convenience of mobile devices has driven the widespread use of voice technology in mobile health communication, significantly improving the timeliness of online service. However, the issue of listening to therapeutic content, which requires great cognitive effort and may exceed the patient's information processing capacity (i.e., information overload), is of concern. Based on information processing theory, this study reports how online physicians' voice characteristics (pitch range and filled pauses) affect patient satisfaction. We obtained 10,585 mobile voice consultation records of 1,416 doctors from China's largest mHealth platform and analyzed them using audio mining and empirical methods. Results showed that pitch range (ß = 0.0539, p < .01) and filled pauses (ß = 0.0365, p < .01) in doctors' voice positively influenced online patient satisfaction. However, the effect of filled pauses becomes weaker for patients with higher health literacy and higher disease risk. This suggests that there is heterogeneity in the way different patients process audio information. This study provides important insights for guiding online physician behaviors, enhancing patient satisfaction, and improving mobile health platform management.

A new membrane anatomy-oriented classification of radical surgery for rectal cancer.

For patients with different clinical stages of rectal cancer, tailored surgery is urgently needed. Over the past 10 years, our team has conducted numerous anatomical studies and proposed the "four fasciae and three spaces" theory to guide rectal cancer surgery. Enlightened by the anatomical basis of the radical hysterectomy classification system of Querleu and Morrow, we proposed a new classification system of radical surgery for rectal cancer based on membrane anatomy. This system categorizes the surgery into four types (A-D) and incorporates corresponding subtypes based on the preservation of the autonomic nerve. Our surgical classification unifies the pelvic membrane anatomical terminology, validates the feasibility of classifying rectal cancer surgery using the theory of "four fasciae and three spaces," and lays the theoretical groundwork for the future development of unified and standardized classification of radical pelvic tumor surgery.

New classification system for radical rectal cancer surgery based on membrane anatomy.

BACKGROUND: Total mesorectal excision along the "holy plane" is the only radical surgery for rectal cancer, regardless of tumor size, localization or even tumor stage. However, according to the concept of membrane anatomy, multiple fascial spaces around the rectum could be used as the surgical plane to achieve radical resection. AIM: To propose a new membrane anatomical and staging-oriented classification system for tailoring the radicality during rectal cancer surgery. METHODS: A three-dimensional template of the member anatomy of the pelvis was established, and the existing anatomical nomenclatures were clarified by cadaveric dissection study and laparoscopic surgical observation. Then, we suggested a new and simple classification system for rectal cancer surgery. For simplification, the classification was based only on the lateral extent of resection. RESULTS: The fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side around the rectum and form three spaces (medial, middle and lateral), and blood vessels and nerves are precisely positioned in the fascia or space. Three types of radical surgery for rectal cancer are described, as are a few subtypes that consider nerve preservation. The surgical planes of the proposed radical surgeries (types A, B and C) correspond exactly to the medial, middle, and lateral spaces, respectively. CONCLUSION: Three types of radical surgery can be precisely defined based on membrane anatomy, including nerve-sparing procedures. Our classification system may offer an optimal tool for tailoring rectal cancer surgery.

Physicians' Online Writing Language Style and Patient Satisfaction: The Mediator of Depth of Physician-Patient Interactions.

Online health counseling (OHC) is increasingly important in modern healthcare. This development has attracted considerable attention from researchers. However, the reality of the lack of physician-patient communication and dissatisfaction with online health services remains prevalent, and more research is needed to raise awareness about important issues related to OHC services, especially in terms of patient satisfaction and depth of interaction (i.e., the product of the number of interactions and the relevance of the content). This study constructs an empirical model to explore the relationship between physicians' online writing language style (inclusive language and emojis), depth of physician-patient interactions, and patient satisfaction. The study obtained 5064 online health counseling records from 337 pediatricians and analyzed them using text mining and empirical methods. The results showed that physicians' inclusive language (ß = 0.3198, p < 0.05) and emojis (ß = 0.6059, p < 0.01) had a positive impact on patient satisfaction. In addition, the depth of the physician-patient interaction partially mediated this effect. This study promotes a better understanding of the mechanisms of physician-patient interactions in online settings and has important implications for how online physicians and platforms can better provide online healthcare services.

Laparoscopic Lateral Lymph Node Dissection Based on Membrane Anatomy for Lower Rectal Cancer: Surgical Technique and Short-Term Outcomes.

Background: Lateral lymph node dissection (LLND) is an effective treatment for metastatic lateral lymph nodes (LLNs) in lower rectal cancer, but with high complication rates due to a complicated procedure. This study aimed to introduce a new technique for LLND based on membrane anatomy to simplify the procedure and report short-term outcomes. Methods: Twenty-three patients with clinical stage II-III lower rectal cancer underwent three-dimensional (3D) laparoscopic total mesorectal excision (TME) plus LLND between July 2018 and December 2020. Demographic data, perioperative variables, and oncologic outcomes were recorded and analyzed. Complications were graded using the Clavien-Dindo (CD) score. Results: Based on the theory of "four fasciae and three spaces," we proposed a fascia-to-space surgical approach to perform LLND. 3D laparoscopic TME plus LLND was performed successfully in all patients. The mean operating time was 172 minutes with a mean blood loss of 85 mL. Postoperative complications were present in 5 (17.4%) patients (CD I-II), including a case of urinary retention. The median number of harvested LLNs was 9, and positive LLNs were detected in 7 (30.4%) patients. After a median follow-up of 26.5 months, 2 (8.7%) patients developed liver metastases, but no local recurrence. Conclusions: Laparoscopic LLND based on membrane anatomy is a safe, feasible, and reproducible procedure and thus worthy of clinical promotion. Further studies with long-term follow-up in larger patient series are still required.

Alcohol dehydrogenase 4 is a TP53-associated gene signature for the prediction of prognosis in hepatocellular carcinoma.

Tumor protein p53 (TP53) is one of the most frequently mutated genes in hepatocellular carcinoma (HCC), an event that has been associated with a poor prognosis. Therefore, availability of an accurate prognostic signature would be beneficial for improving therapeutic efficacy and patient prognosis. In the present study, HCC genetic mutation data, transcriptomic data and clinical data were downloaded from The Cancer Genome Atlas database to screen for specific TP53-associated signatures based on differentially expressed genes. Subsequently, the predictive value of any signatures found for the overall survival (OS) and the immune response were investigated, followed by validation in clinical specimens. The present study revealed 270 mutant genes, of which 28% were TP53 mutations. In addition, 81 upregulated genes and 27 downregulated genes were identified. Enrichment analysis revealed that mutant TP53 was particularly enriched for pathways associated with the cell cycle and cell metabolism, and whilst clustered, most enriched for terms associated with metabolic processes and the immune response. The alcohol dehydrogenase 4 (ADH4) gene was selected using univariate and multivariate Cox regression analysis. A nomogram was constructed to validate this prognostic signature. Patients in the low-ADH4 expression group displayed significantly worse OS time regardless of the TP53 mutation status compared with the high-ADH4 expression group. In addition, a higher degree of B-cell infiltration was observed in the low-ADH4 expression group, revealing differential immune microenvironments. Subsequently, ADH4 expression and the prognostic prediction values were validated further in clinical HCC samples by IHC assay, Risk score, OS analysis and ROC analysis. To conclude, these data suggest that the TP53-associated immune-metabolic signature is a specific and independent prognostic biomarker for patients with HCC that will help to facilitate novel immunotherapy development.

The Impact of Popular Science Articles by Physicians on Their Performance on Online Medical Platforms.

The public demand for popular science knowledge regarding health is increasing, and physicians' popular science practices on online medical platforms are becoming frequent. Few studies have been conducted to address the relationship between specific characteristics of popular science articles by physicians and their performance. This study explored the impact of the characteristics of popular science articles on physicians' performance based on the elaboration likelihood model (ELM) from the central path (topic focus and readability) and the peripheral path (form diversity). Data on four diseases, namely, lung cancer, brain hemorrhage, hypertension, and depression, were collected from an online medical platform, resulting in relevant personal data from 1295 doctors and their published popular science articles. Subsequently, the independent variables were quantified using thematic analysis and formula calculation, and the research model and hypotheses proposed in this paper were verified through empirical analysis. The results revealed that the topic focus, readability, and form diversity of popular science articles by physicians had a significant positive effect on physicians' performance. This study enriches the research perspective on the factors influencing physicians' performance, which has guiding implications for both physicians and platforms, thereby providing a basis for patients to choose physicians and enabling patients to receive popular science knowledge regarding health in an effective manner.

Novel multiplex stool-based assay for the detection of early-stage colon cancer in a Chinese population.

BACKGROUND: Stool DNA (sDNA) methylation analysis is a promising, noninvasive approach for colorectal cancer screening; however, reliable biomarkers for detecting early-stage colon cancer (ECC) are lacking, particularly in the Chinese population. AIM: To identify a novel stool-based assay that can improve the effectiveness of ECC screening. METHODS: A blinded case-control study was performed using archived stool samples from 125 ECC patients, and 125 control subjects with normal colonoscopy. The cohort was randomly divided into training and test sets at a 1.5:1 ratio. Targeted bisulfite sequencing (TBSeq) was conducted on five pairs of preoperative and postop-erative sDNA samples from ECC patients to identify DNA methylation biomarkers, which were validated using pyrosequencing. By logistic regression analysis, a multiplex stool-based assay was developed in the training set, and the detection performance was further assessed in the test set and combined set. The χ 2 test was used to investigate the association of detection sensitivity with clinico-pathological features. RESULTS: Following TBSeq, three hypermethylated cytosine-guanine sites were selected as biomarkers, including paired box 8, Ras-association domain family 1 and secreted frizzled-related protein 2, which differed between the groups and were involved in important cancer pathways. An sDNA panel containing the three biomarkers was constructed with a logistic model. Receiver operating characteristic (ROC) analysis revealed that this panel was superior to the fecal immunochemical test (FIT) or serum carcinoembryonic antigen for the detection of ECC. We further found that the combination of the sDNA panel with FIT could improve the screening effectiveness. In the combined set, the sensitivity, specificity and area under the ROC curve for this multiplex assay were 80.0%, 93.6% and 0.918, respectively, and the performance remained excellent in the subgroup analysis by tumor stage. In addition, the detection sensitivity did not differ with tumor site, tumor stage, histological differentiation, age or sex, but was significantly higher in T4 than in T1-3 stage tumors (P = 0.041). CONCLUSION: We identified a novel multiplex stool-based assay combining sDNA methylation biomarkers and FIT, which could detect ECC with high sensitivity and specificity throughout the colon, showing a promising application perspective.

Detecting Suicidal Ideation in Social Media: An Ensemble Method Based on Feature Fusion.

Suicide has become a serious problem, and how to prevent suicide has become a very important research topic. Social media provides an ideal platform for monitoring suicidal ideation. This paper presents an integrated model for multidimensional information fusion. By integrating the best classification models determined by single and multiple features, different feature information is combined to better identify suicidal posts in online social media. This approach was assessed with a dataset formed from 40,222 posts annotated by Weibo. By integrating the best classification model of single features and multidimensional features, the proposed model ((BSC + RFS)-fs, WEC-fs) achieved 80.61% accuracy and a 79.20% F1-score. Other representative text information representation methods and demographic factors related to suicide may also be important predictors of suicide, which were not considered in this study. To the best of our knowledge, this is the good try that feature combination and ensemble algorithms have been fused to detect user-generated content with suicidal ideation. The findings suggest that feature combinations do not always work well, and that an appropriate combination strategy can make classification models work better. There are differences in the information contained in different functional carriers, and a targeted choice classification model may improve the detection rate of suicidal ideation.

Clinical features and management of 20 patients with hepatic portal venous gas.

The present study investigated the characteristics, diagnosis, treatment and prognosis of hepatic portal venous gas (HPVG) using the data of 20 patients from the Tongji University School of Medicine Affiliated with Yangpu Hospital (Shanghai, China). The aim of the present study was to optimize the management method and improve the prognosis of patients with HPVG. A total of 20 patients were selected using a CT scan to confirm HPVG. All patients were enrolled and identified via a search engine, which examined all CT radiology reports containing the words pneumatosis and/or portal venous gas/air. Data were collected and analyzed, including sex, age, laboratory evidence, etiologies at admission, therapeutic method and in-hospital mortality. The patients consisted of 14 women (mean age, 79.1 years) and six men (mean age, 67.8 years). The results demonstrated that HPVG indicated a higher inflammatory index. The etiologies of HPVG included abdominal infection, pulmonary infection and hemorrhage, whereas the comorbidities included hypertension, diabetes, coronary disease, cerebrovascular disease and renal insufficiency. The present study determined that intestinal obstruction, acute enteritis and pulmonary infection were the main causes of HPVG. Of the 20 patients enrolled in the present study, four patients received surgery and 16 patients received conservative treatment. The overall in-hospital mortality was 25%. The present study indicated that the causes of HPVG may be closely related to inflammation and blood vessel injury. It was also determined that hemodynamic disorders of the intestinal tract and the combination of different types of infection were important contributors towards patient mortality.

Genomic profiling identifies genes and pathways dysregulated by HEY1-NCOA2 fusion and shines a light on mesenchymal chondrosarcoma tumorigenesis.

Mesenchymal chondrosarcoma is a rare, high-grade, primitive mesenchymal tumor. It accounts for around 2-10% of all chondrosarcomas and mainly affects adolescents and young adults. We previously described the HEY1-NCOA2 as a recurrent gene fusion in mesenchymal chondrosarcoma, an important breakthrough for characterizing this disease; however, little study had been done to characterize the fusion protein functionally, in large part due to a lack of suitable models for evaluating the impact of HEY1-NCOA2 expression in the appropriate cellular context. We used iPSC-derived mesenchymal stem cells (iPSC-MSCs), which can differentiate into chondrocytes, and generated stable transduced iPSC-MSCs with inducible expression of HEY1-NCOA2 fusion protein, wildtype HEY1 or wildtype NCOA2. We next comprehensively analyzed both the DNA binding properties and transcriptional impact of HEY1-NCOA2 expression by integrating genome-wide chromatin immunoprecipitation sequencing (ChIP-seq) and expression profiling (RNA-seq). We demonstrated that HEY1-NCOA2 fusion protein preferentially binds to promoter regions of canonical HEY1 targets, resulting in transactivation of HEY1 targets, and significantly enhances cell proliferation. Intriguingly, we identified that both PDGFB and PDGFRA were directly targeted and upregulated by HEY1-NCOA2; and the fusion protein, but not wildtype HEY1 or NCOA2, dramatically increased the level of phospho-AKT (Ser473). Our findings provide a rationale for exploring PDGF/PI3K/AKT inhibition in treating mesenchymal chondrosarcoma. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

Laparoscopic total mesorectal excision with urogenital fascia preservation for mid-low rectal cancer: Anatomical basis and clinical effect - Experimental research.

BACKGROUND: Total mesorectal excision (TME) is conventionally performed according to Heald's principles through the so-called 'holy plane', between the visceral and parietal fasciae. However, urinary and sexual dysfunctions remain frequent postoperative complications. We proposed to preserve urogenital fascia (UGF) in TME, and this study aimed to clarify the anatomical basis of this technique and evaluate its efficacy and safety. MATERIALS AND METHODS: Cadaveric dissection was performed on 26 pelvises, and laparoscopic TME with UGF preservation was performed in 212 patients with mid-low rectal cancer. The fasciae and spaces related to TME were observed and described, and the clinical effect of UGF-preserving TME was analyzed. RESULTS: In the 26 cadavers, fascia propria of the rectum (FPR) presents as a fibrous capsule enveloping the mesorectum. UGF extends postero-laterally to the rectum, enveloping the hypogastric nerves and ureters. We demonstrated that the visceral fascia is actually the UGF, and FPR and visceral fascia (i.e. UGF) are two independent layers of fascia. Thus, FPR, UGF and parietal fascia form two avascular spaces behind the rectum. The plane ventral to the UGF is the real 'holy plane' for TME, rather than that dorsal to the UGF as is traditionally thought. Laparoscopic TME with UGF preservation was successfully performed in all 212 patients, with low perioperative complications (10.8%) and a low 3-year local recurrence rate (4.2%). Furthermore, the incidences of urinary and sexual dysfunctions at postoperative 6 months were only 6.1% and 10.8%, respectively. CONCLUSION: The avascular plane between the FPR and UGF (i.e. visceral fascia) is the real 'holy plane'. Laparoscopic TME with UGF preservation is a feasible radical surgery for mid-low rectal cancer, with better protection of urinary and sexual functions.

Targeted deep sequencing reveals APC mutations as predictors of overall survival in Chinese colorectal patients receiving adjuvant chemotherapy.

Objective: Targeted deep sequencing was used to characterize the mutational spectrum of APC in Chinese colorectal tumors in comparison to that in Caucasians from The Cancer Genome Atlas (TCGA) and to investigate whether APC mutations can predict overall survival in CRC patients receiving adjuvant chemotherapy.Methods: A total of 315 Chinese CRC patients including 241 stage II/III patients receiving fluorouracil-based adjuvant chemotherapy were included in this study. Next generation sequencing was carried out to detect somatic mutations on all APC exons. The associations between APC mutations and overall survival were determined by the Cox proportional hazards model.Results:APC was mutated in 221 of 315 colorectal tumors (70.2%). Chinese CRC had a much higher frequency of missense mutations (16.2% vs. 2.4%), but a lower frequency of nonsense (41.0% vs. 54.2%) and frameshift mutations (10.5% vs. 18.4%) than Caucasian CRC. Among stage II/III patients receiving fluorouracil-based adjuvant chemotherapy, APC mutations showed a significant association with worse survival (HR = 1.69; 95% CI, 1.10-2.62; p = .0179). Of the mutation types, frameshift mutations conferred the highest risk of death (HR = 2.88; 95% CI, 1.54-5.37; p =.0009). Among individual mutation sites, Arg232Ter, the most frequent mutation in Chinese CRC, exhibited the strongest negative impact on survival (HR = 2.65; 95% CI, 1.16-6.03; p =.0202).Conclusion:APC overall mutation was an independent predictor for overall survival of stage II/III CRC patients receiving fluorouracil-based chemotherapy.

Squalene synthase predicts poor prognosis in stage I-III colon adenocarcinoma and synergizes squalene epoxidase to promote tumor progression.

Colon adenocarcinoma (COAD) is one of the most prevalent malignancies, with poor prognosis and lack of effective treatment targets. Squalene synthase (FDFT1) is an upstream enzyme of squalene epoxidase (SQLE) in cholesterol biosynthesis. In a previous study, we revealed that SQLE promotes colon cancer cell proliferation in vitro and in vivo. Here, we investigate the prognostic value of FDFT1 in stage I-III COAD and explore the potential underlying mechanisms. Squalene synthase was significantly upregulated in stage I-III COAD and positively correlated with poor differentiation and advanced tumor stage. High expression of FDFT1 was an independent predictor of overall and relapse-free survival, and the nomograms based on FDFT1 could effectively identify patients at high risk of poor outcome. Squalene synthase accelerated colon cancer cell proliferation and promoted tumor growth. Lack of FDFT1 resulted in accumulating NAT8 and D-pantethine to lower reactive oxygen species levels and inhibit colon cancer cell proliferation. Moreover, the combined inhibition of FDFT1 and SQLE induced a greater suppressive effect on cell proliferation and tumor growth than single inhibition. Taken together, these results indicate that FDFT1 predicts poor prognosis in stage I-III COAD and has the tumor-promoting effect on COAD through regulating NAT8 and D-pantethine. Targeting both FDFT1 and SQLE is a more promising therapy than their single inhibition for stage I-III COAD.

Laparoscopic lateral lymph node dissection in two fascial spaces for locally advanced lower rectal cancer.

BACKGROUND: The procedure for lateral lymph node (LLN) dissection (LLND) is complicated and can result in complications. We developed a technique for laparoscopic LLND based on two fascial spaces to simplify the procedure. AIM: To clarify the anatomical basis of laparoscopic LLND in two fascial spaces and to evaluate its efficacy and safety in treating locally advanced low rectal cancer (LALRC). METHODS: Cadaveric dissection was performed on 24 pelvises, and the fascial composition related to LLND was observed and described. Three dimensional-laparoscopic total mesorectal excision with LLND was performed in 20 patients with LALRC, and their clinical data were analyzed. RESULTS: The cadaver study showed that the fascia propria of the rectum, urogenital fascia, vesicohypogastric fascia and parietal fascia lie side by side in a medial-lateral direction constituting the dissection plane for curative rectal cancer surgery, and the last three fasciae formed two spaces (Latzko's pararectal space and paravesical space) which were the surgical area for LLND. Laparoscopic LLND in two fascial spaces was performed successfully in all 20 patients. The median operating time, blood loss and postoperative hospitalization were 178 (152-243) min, 55 (25-150) mL and 10 (7-20) d, respectively. The median number of harvested LLNs was 8.6 (6-12), and pathologically positive LLN metastasis was confirmed in 7 (35.0%) cases. Postoperative complications included lower limb pain in 1 case and lymph leakage in 1 case. CONCLUSION: Our preliminary surgical experience suggests that laparoscopic LLND based on fascial spaces is a feasible, effective and safe procedure for treating LALRC.

Ultrastretchable, self-adhesive, strain-sensitive and self-healing GO@DA/Alginate/P(AAc-co-AAm) multifunctional hydrogels via mussel-inspired chemistry.

For conductive hydrogels applied in biosensors, wearable devices and so forth, multifunctionality is an inevitable trend of development to meet various practical requirements and enhance human experience. Herein, inspired by nanocomposite, double-network (DN) and mussel chemistry, a new Graphene oxide@Dopamine/Alginate/Poly(acrylic acid-co-acrylamide) [GO@DA/Alginate/P(AAc-co-AAm)] hydrogel was fabricated through one-pot in-situ radical copolymerization. GO@DA nanofillers, prepared via GO confined DA polymerization, imparted the hydrogel with remarkable adhesiveness. Alginate/P(AAc-co-AAm) DN matrix, physically and chemically crosslinked by Fe3+ and N,N'-Methylenebisacrylamide, made hydrogels ultrastretchable, self-healing and biocompatible. With contents of DA and alginate accurately regulated, the tensile strength, elongation, adhesion strength and conductivity of the optimal hydrogel could reach 320.2 kPa, 1198 %, 36.9 kPa and 3.24 ± 0.12 S/m, respectively. What's more notable was that the synergistic integration of repeatable adhesiveness, strain sensitivity, use stability, self-healing ability and biocompatibility provided such hydrogels with tremendous possibility of practical application for strain sensors.

Comparative mutational analysis of distal colon cancer with rectal cancer.

Distal colon and rectal cancer are associated with each other but display distinct clinical behavior; however, the genetic basis for these differences is poorly understood. In the present study, a systematic comparison of mutational profiles between 137 distal colon and 125 rectal cancer samples was performed based on the data from the Memorial Sloan Kettering Cancer Center. Tumor mutational burden analysis showed that distal colon and rectal cancer harbored a similar burden of ~5.9 mutations/megabase, irrespective of the mismatch repair status. Comparison of significantly mutated genes between the groups determined that B-Raf proto-oncogene serine/threonine kinase mutations were enriched in distal colon cancer, whilst RAS and SMAD family member 4 (SMAD4) mutations were significantly more frequent in rectal cancer. Furthermore, two novel and potentially targetable hotspot mutations (APC regulator of WNT signaling pathway R876* and SMAD4 R361) were identified, which were enriched in rectal cancer compared with distal colon cancer. Overall, the results of the present study showed that the mutation profiles of distal colon and rectal cancer were largely similar, but distinct in specific key genetic events, which may provide valuable information for improving the management of patients with the disease.

Comparison of surgical outcomes between video-assisted anal fistula treatment and fistulotomy plus seton for complex anal fistula: A propensity score matching analysis - Retrospective cohort study.

BACKGROUND: Video-assisted anal fistula treatment (VAAFT) is a new minimally invasive technique for treating complex anal fistula (CAF). This study aimed to compare the efficacy and safety of VAAFT with fistulotomy plus seton (FPS) for treatment of CAF. MATERIALS AND METHODS: We included 148 patients with CAF receiving surgical treatment at our hospital between January 2017 and December 2018. Propensity score matching (PSM) analysis was conducted with patients' baseline characteristics, and surgical outcomes were compared between the matched groups. Logistic analysis was performed to identify the risk factors for fistula recurrence after VAAFT. RESULTS: Among the study population, 68 and 80 patients underwent VAAFT and FPS, respectively. After PSM, 64 matched pairs of patients were created with no significant differences in baseline characteristics. Compared with FPS, VAAFT had greater efficiency of locating internal openings (90.6% vs. 100%), less intraoperative blood loss (26 ± 15 vs. 12 ± 5 mL), lower incidence of postoperative bleeding (10.9% vs. 1.5%), shorter postoperative hospital stay (6.8 ± 5.1 vs. 5.0 ± 3.3 days), reduced postoperative pain, and decreased wound secretion (all P < 0.05). VAAFT showed a significantly lower Wexner incontinence score than FPS (0.9 ± 1.7 vs. 1.9 ± 2.6, P = 0.003) at 3 months postoperatively, but no significant difference in the healing rate was observed either at 3-month or 1-year (P = 1.000) follow-up. A total of 12 patients (17.6%) developed fistula recurrence after VAAFT, and logistic analysis revealed that multiple fistula tracts, prolonged operating time and severe postoperative wound secretion were independent risk factors (odds risk = 2.18, 3.25 and 3.04, respectively, all adjusted P < 0.05). CONCLUSION: Compared with FPS, VAAFT offers some advantages for treatment of CAF, including minimal damage, less pain, rapid recovery, fewer complications and better sphincter preservation.

Rhein induces liver cancer cells apoptosis via activating ROS-dependent JNK/Jun/caspase-3 signaling pathway.

Background: Liver cancer is one of the leading cancers in China. Rhein induces apoptosis in various human cancer cells, but the underlying mechanism is still unknown. Methods: In the present study, the MTT assay was used to detect the anti-cell growth ability of Rhein on liver cancer cells. Hoechst33342 staining and FACS assay were used to detect cell apoptosis. Finally, the effect of Rhein on JNK protein' phosphorylation level and the apoptosis-associated proteins were determined by western blot. Results: Here, we found that Rhein significantly inhibited the cell viability in a dose-dependent and time-dependent manner both in HepG2 and Huh7 cells. Also, Rhein increased the apoptosis, mitochondrial membrane potential (MMP) and cell-cycle arrest. Furthermore, we observed that the ROS level and JNK/Jun/caspase-3 signaling pathway played a key role in Rhein induced apoptosis. Our study further demonstrated that Rhein increases apoptosis by inducing the generation of ROS and activating the JNK/Jun/caspase-3 signaling pathway. Conclusions: The present study showed that Rhein promotes apoptosis via regulating ROS/JNK/Jun/caspase-3 signaling pathway both in HepG2 and Huh7 cells. Rhein may be a promising therapeutic candidate for the treatment of liver cancer.