VV116 versus Nirmatrelvir-Ritonavir for Oral Treatment of Covid-19.

BACKGROUND: Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir). RESULTS: A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%). CONCLUSIONS: Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).

Oncologic outcomes of single-incision laparoscopic surgery versus conventional laparoscopic surgery for colorectal cancer (CSILS): study protocol for a multicentre, prospective, open-label, noninferiority, randomized controlled trial.

BACKGROUND: In most previous studies, single-incision laparoscopic surgery (SILS) for colorectal cancer (CRC) was feasible and safe in the short term. However, long-term oncologic outcomes remain uncertain, as only a few studies contained long-term survival data. SILS for CRC is still in the early stages of research. Further studies, particularly large-scale, prospective randomized controlled trials, are necessary to assess the value of SILS for CRC. METHODS: This study is a prospective, multicentre, open-label, noninferiority, parallel-group randomized controlled trial that investigates the long-term oncologic outcomes of SILS compared to conventional laparoscopic surgery (CLS) for CRC. A total of 710 eligible patients will be randomly assigned to the SILS group or the CLS group at a 1:1 ratio using a central, dynamic, and stratified block randomization method. Patients with ages ranging from 18 to 85 years old, of both sexes, with CRC above the peritoneal reflection diagnosed as cT1-4aN0-2M0 and a tumour size no larger than 5 cm will be considered for the study. The primary endpoint is 3-year disease-free survival (DFS). The secondary endpoints include: intraoperative outcomes, postoperative recovery, postoperative pain assessment, pathological outcomes, early morbidity and mortality rate, cosmetic effects, quality of life, 3-year overall survival (OS), incidence of incisional hernia, 5-year DFS and 5-year OS. The first two follow-up visits will be scheduled at one month and three months postoperatively, then every three months for the first two years and every six months for the next three years. DISCUSSION: Currently, no randomized controlled trials (RCTs) have been designed to investigate the long-term oncologic outcomes of SILS for CRC. This study is expected to provide clinical evidence of the oncologic outcomes of SILS compared to CLS for CRC to promote its widespread use. TRIAL REGISTRATION: ClinicalTrials.gov:  NCT04527861 (registered on August 27, 2020).

Discovering the molecular differences between right- and left-sided colon cancer using machine learning methods.

BACKGROUND: In recent years, the differences between left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have received increasing attention due to the clinicopathological variation between them. However, some of these differences have remained unclear and conflicting results have been reported. METHODS: From The Cancer Genome Atlas (TCGA), we obtained RNA sequencing data and gene mutation data on 323 and 283 colon cancer patients, respectively. Differential analysis was firstly done on gene expression data and mutation data between LCC and RCC, separately. Machine learning (ML) methods were then used to select key genes or mutations as features to construct models to classify LCC and RCC patients. Finally, we conducted correlation analysis to identify the correlations between differentially expressed genes (DEGs) and mutations using logistic regression (LR) models. RESULTS: We found distinct gene mutation and expression patterns between LCC and RCC patients and further selected the 30 most important mutations and 17 most important gene expression features using ML methods. The classification models created using these features classified LCC and RCC patients with high accuracy (areas under the curve (AUC) of 0.8 and 0.96 for mutation and gene expression data, respectively). The expression of PRAC1 and BRAF V600E mutation (rs113488022) were the most important feature for each model. Correlations of mutations and gene expression data were also identified using LR models. Among them, rs113488022 was found to have significance relevance to the expression of four genes, and thus should be focused on in further study. CONCLUSIONS: On the basis of ML methods, we found some key molecular differences between LCC and RCC, which could differentiate these two groups of patients with high accuracy. These differences might be key factors behind the variation in clinical features between LCC and RCC and thus help to improve treatment, such as determining the appropriate therapy for patients.

Clinical and oncological outcomes of single-incision vs. conventional laparoscopic surgery for rectal cancer.

BACKGROUND: To evaluate the clinical and oncological outcomes of single-incision laparoscopic surgery (SILS) vs. conventional laparoscopic surgery (CLS) for patients with rectal cancer (RC) who underwent total mesorectal excision (TME) surgery. METHODS: This was a retrospective case-control study of patients with RC operated between 12/2013 and 12/2017 in Ruijin Hospital North, Shanghai Jiaotong University School of Medicine. In total, 177 patients who underwent CLS and 51 who underwent SILS met the inclusion and exclusion criteria and were matched 1:1 using propensity score matching method (PSM). RESULTS: Compared with the CLS group, the SILS group showed shorter operation time [105 (40) vs. 125 (55) min, P = 0.045], shorter total incision length [4 (1) vs. 6.5 (1.5) cm, P < 0.001], lower VAS score on POD2 [1 (1) vs. 2 (1), P < 0.001], shorter time to soft diet [7 (1) vs. 8 (2) days, P = 0.048], and shorter length of hospital stay [9 (2) vs. 11 (3) days, P < 0.001]. The postoperative complications were similar between two groups [1(2%) vs. 5 (9.8%), P = 0.205]. No readmissions or mortality in either group occurred within 30 days of surgery. All 102 specimens met the requirements of TME. No significant differences were observed in the pathologic outcomes between the two groups. The median follow-up period was 32.6 months in the SILS group and 36.8 months in the CLS group (P = 0.053). The 3-year disease-free survival rates and overall survival rates of the SILS and CLS groups were 89.8% vs. 96.0% (P = 0.224) and 90.9% vs. 96.9% (P = 0.146), respectively. CONCLUSIONS: Compared with CLS, TME surgery for rectal cancer can be performed safely and effectively using the SILS technique with better cosmetic results, less postoperative pain, faster postoperative recovery, and acceptable clinical and oncological outcomes.

Clinical and oncologic outcomes of single-incision laparoscopic surgery for right colon cancer: a propensity score matching analysis.

BACKGROUND: Single-incision laparoscopic surgery (SILS) for right colon cancer is going to be considered as a new option. The potential benefits, clinical, and oncologic outcomes are still controversial. The aim of this study was to investigate clinical and oncologic outcomes of single-incision laparoscopic surgery (SILS) compared to conventional laparoscopic surgery (CLS) for right colon cancer using propensity score matching analysis. METHODS: From December 2013 to June 2017, 174 patients underwent laparoscopic radical right hemicolectomy through a single-incision (n = 32) or a conventional (n = 142) approach. The data were prospectively collected and the patients were matched at a radio of 1:1 according to age, sex, body mass index (BMI), previous abdominal surgeries, comorbidities, ASA score (≤ 2/> 2), and pathologic stage. RESULTS: No significant differences were observed in estimated blood loss, time to diet, postoperative pain score, length of hospital stay between the SILS and CLS groups. However, the SILS group showed longer operation time (175 (40) vs 145 (52.5), p = 0.011) and shorter incision length (4 (1.4) vs 7 (1.9), p < 0.001). There were 2 (6.3%) postoperative complications in the SILS group and 5 (15.6%) in the CLS group (p = 0.426). The pathologic outcomes were similar between two groups. The median follow-up period was 26.5 months in the SILS group and 34.9 months in the CLS group (p = 0.002). There were 3 recurrences (9.4%) in the SILS group and 3 (9.4%) in the CLS group. The 3-year disease-free survival rates were 92.4 and 93.8% (p = 0.984), and overall survival rates were 92.3 and 93.0% (p = 0.884) in the SILS and the CLS groups, respectively. No incisional hernia was observed during the follow-up period. CONCLUSIONS: Though single-incision laparoscopic surgery for right colon cancer showed longer operation time in this study, it appears to be a safe and feasible option with comparable clinical and oncologic outcomes to conventional laparoscopic surgery.

Co/P co-doped bamboo-based woodceramics with a sandwich structure modified by carbon nanotube electrodeposition as supercapacitor electrodes.

Exploring new electrode structures and co-doped composite biomass material electrodes is considered to be an effective way of developing cheap, efficient carbon-based supercapacitors. A bamboo-based sandwich-structured matrix was prepared from thin bamboo veneer and bamboo fiber by pretreatment with H3PO4 and Co2+-catalyzed graphitization. The pore structure was modulated by hydrothermal activation with NaOH and electrodeposition of carbon nanotubes (CNTs) to obtain CNTs modified, Co/P co-doped sandwich-structured woodceramics electrode (CNT@Co/P). It not only has an obvious sandwich structure, but also retains the natural structural characteristics of bamboo. The specific capacitance of the resulting electrode (CNT@Co/P-20) is as high as 453.72F/g using 1 wt% of carboxylated multi-walled carbon nanotubes (CMWCNT) solution as the deposition electrolyte at a current density of 0.2 A/g for 20 min at room temperature. When the power density is 500 W/kg, the energy density reaches 21.3Wh /kg, showing a good electrochemical performance.

Protective effect of MP-40 mitigates BDL-induced hepatic fibrosis by inhibiting the NLRP3-mediated pyroptosis.

Background: Hepatic fibrosis and its associated consequences continue to pose a substantial global health challenge. Developing novel approaches to hepatic fibrosis management and prevention is critically necessary. Radix Paeoniae Alba (RPA) is widely used in Traditional Chinese Medicine (TCM) to treat various diseases. Our earlier research found that a bioactive component of RPA had a dose-dependent effect on anti-allergic asthma. RPA reduces allergic asthma by slowing the hepatic wind, according to "Treatise on Febrile Diseases". However, this bioactive fraction's pharmacological effects and mechanisms on the liver are unknown. Aim: This study examined the bioactive fraction MP-40, the methanol extract of RPA (MRPA), on bile duct ligation (BDL) for its anti-hepatic fibrosis activity and potential mechanisms. Methods: First, the effectiveness of MP-40 in treating BDL-induced hepatic fibrosis in mice and rats was evaluated through survival rates, ALT, AST HYP, and pathological changes. Molecular assays were performed using in vitro cultures of HSC-T6 activation. The expression of α-SMA and Collagen I evaluated fibro-tropic factors with HSC activation. Furthermore, the levels of pyroptosis were assessed by examining the expression of the pyroptosis-related proteins, including NLRP3, Cleaved Caspase-1, GSDMD-N, and 1L-1ß. Additionally, the effective constituents of MP-40 were identified by extraction, separation, and identification. Finally, PF and TGG, as the delegate compounds of MP-40, were tested to confirm their inhibition effects on HSC-T6 activation. Results: The findings demonstrated that MP-40 and MRPA could lower ALT, AST, and HYP levels, boost survival rates, and reduce liver damage in BDL mice and rats. Furthermore, MP-40 outperforms MRPA. MP-40 was proven to drastically diminish fibrotic α-SMA and Collagen I. The expression of pyroptosis-related proteins NLRP3, Cleaved Caspase-1, TGF-ß1, GSDMD-N, and 1L-1ß decreased. MP-40 inhibited the synthesis of pyroptosis-related proteins more effectively than MCC950 (an NLRP3-specific inhibitor). Monoterpene glycosides and tannins were shown to be the most potent MP-40 components. Finally, the delegate compounds MP-40, PF, and TGG were shown to have substantial inhibitory effects on HSC-T6 activation. Conclusion: The results proved that MP-40 alleviates BDL-induced cholestatic hepatic fibrosis by inhibiting NLRP3-mediated pyroptosis. PF and TGG play a role in treating BDL-induced cholestatic hepatic fibrosis in MP-40.

Learning matrix factorization with scalable distance metric and regularizer.

Matrix factorization has always been an encouraging field, which attempts to extract discriminative features from high-dimensional data. However, it suffers from negative generalization ability and high computational complexity when handling large-scale data. In this paper, we propose a learnable deep matrix factorization via the projected gradient descent method, which learns multi-layer low-rank factors from scalable metric distances and flexible regularizers. Accordingly, solving a constrained matrix factorization problem is equivalently transformed into training a neural network with an appropriate activation function induced from the projection onto a feasible set. Distinct from other neural networks, the proposed method activates the connected weights not just the hidden layers. As a result, it is proved that the proposed method can learn several existing well-known matrix factorizations, including singular value decomposition, convex, nonnegative and semi-nonnegative matrix factorizations. Finally, comprehensive experiments demonstrate the superiority of the proposed method against other state-of-the-arts.

Single-incision robotic assisted surgery: a nonrandomized cohort pilot study on a novel surgical platform in colorectal surgery.

BACKGROUND: The technological barriers and steep learning curve of single-incision laparoscopic surgery had kept it from further applications. A literature review had reported that robotic technology could preserve its advantages while simplifying its difficulties. This nonrandomized cohort pilot study aims to evaluate the feasibility and safety of single-incision robotic assisted colorectal surgery based on a novel robotic surgical platform, the SHURUI Endoscopic Surgical Robotic System (SR-ENS-600). METHOD: This study enrolled 7 patients with colorectal malignancy who underwent single-incision robotic assisted surgery (SIRAS) at a tertiary general surgery center, and retrospectively included 23 patients who underwent robotic assisted surgery from September 2015 to June 2016 and 35 patients who underwent single-incision laparoscopic surgery from June 2017 to March 2018, which were labeled as the initial in-learning-curve attempts from the same surgical team. The technological feasibility and safety of SIRAS were evaluated. Perioperative outcomes, short-term postoperative outcomes, clinicopathologic outcomes, and follow-up were reported. RESULTS: Six SIRAS operations were completed successfully without eventful intraoperative complications, except for one operation that encountered a large-volume of intraoperative hemorrhage. Two SIRAS cases were converted to multiport laparoscopic surgery because of intraoperative hemorrhage and difficulty in retraction. Postoperative pathology reported satisfactory specimen qualities. There were no short-term postoperative complications, no short-term mortality, no tumor recurrence, or metastasis reported. There was one incisional hernia reported half a year after operation. Patients with advanced staging were sent to standard evaluation and chemotherapy, and follow-up is still on-going. CONCLUSIONS: SIRAS can be feasibly performed by a skilled surgical team via the SR-ENS-600 platform for strictly-selected patients, which provides preferable instrument maneuverability and stability in confined surgical fields and overcomes the technical difficulty of multisite dissection through a single-incision. Large-volume investigations and high-level evidences are required to further validate its safety and superiority.

Clinical status and future prospects of single-incision robotic-assisted surgery: a review.

Since the advent of conventional multiport laparoscopic surgery, the prosperity of minimally invasive surgery has been thriving on the advancement of endoscopic techniques. Cosmetic superiority, recovery benefits, and noninferior surgical outcomes weigh single-incision laparoscopic surgery as a promising modality. Although there are surgical challenges posed by steep learning curve and technological difficulties, such as instruments collision, triangulation loss and limited retraction, the establishment of robotic surgical platform as a solution to all is inspiring. Furthermore, with enhanced instrument maneuverability and stability, robotic ergonomic innovations adopt the advantages of single-incision laparoscopic surgery and surmount its recognized barriers by introducing a novel combination, single-incision robotic-assisted surgery. As was gradually diffused in general surgery and other specialties, single-incision robotic-assisted surgery manifests privileges in noninferior clinical outcomes an satisfactory cosmetic effect among strictly selected patients, and has the potential of a preferable surgical option for minimally invasive surgery.

Pure transvaginal natural orifice transluminal endoscopic surgery right hemicolectomy for colon cancer: A case report.

BACKGROUND: Pure natural orifice transluminal endoscopic surgery (NOTES) for colorectal cancer is a complex procedure and rarely used in clinical practice because of the ethical concerns and technical challenges, including loss of triangulation, in-line orientation, and instrument collision. Transvaginal (v) NOTES, however, can overcome these technical challenges. We report a case of pure vNOTES right hemicolectomy for colon cancer, attached with surgical video. CASE SUMMARY: A 65-year-old woman with a 2-year history of intermittent diarrhea was diagnosed with ascending colon adenocarcinoma by colonoscopy and biopsy. Pure vNOTES right hemicolectomy was performed with complete mesocolic excision by well-experienced surgeons. The operative time was 200 min and the estimated blood loss was 30 mL. No intraoperative or postoperative complications occurred within 30 d after the surgery. The visual analog scale pain score on postoperative day 1 was 1 and dropped to 0 on postoperative days 2 and 3. The patient was discharged at postoperative day 6. The pathologic specimen had sufficient clear resection margins and 14 negative harvested lymph nodes. CONCLUSION: vNOTES right hemicolectomy, performed by well-experienced surgeons, overcomes the technical challenges of pure NOTES and may be feasible for colon cancer.

Comparative Effectiveness of Enhanced Recovery After Surgery Program Combined With Single-Incision Laparoscopic Surgery in Colorectal Cancer Surgery: A Retrospective Analysis.

BACKGROUND: Recently, enhanced recovery after surgery (ERAS) has been widely used in the perioperative management of colorectal cancer (CRC). This study aimed to evaluate the safety and feasibility of ERAS combined with single-incision laparoscopic surgery (SILS) in CRC surgery. METHODS: This was a retrospective study of patients with CRC who underwent surgery between April 2018 and April 2020 in Ruijin Hospital(North), Shanghai Jiaotong University School of Medicine. The patients were divided into three groups: group A (n=138), patients who underwent traditional multiport laparoscopic colectomy with conventional perioperative management; group B (n=63), patients who underwent SILS; and group C (n=51), patients who underwent SILS with ERAS. RESULTS: Overall, 252 participants were included in the retrospective study. The median operation time (min) in group B and group C was shorter than that in group A (group A 134.0 ± 42.5; group B 117 ± 38.9; group C 111.7 ± 35.4, p=0.004). The estimated surgical blood loss (ml) was lower in groups B and C than in group A (group A 165.1 ± 142.2; group B 122.0 ± 79.4; group C 105.2 ± 55.8, p=0.011). The length of surgical incision (cm) was shorter in groups B and C than in group A (group A 7.34 ± 1.05; group B 5.60 ± 0.80; group C 5.28 ± 0.52, p<0.001). The time before first flatus (hours) in group C was shorter than in groups A and B (group A 61.85 ± 21.14; group B 58.30 ± 20.08; group C 42.06 ± 23.72; p<0.001). The days prior to the administration of free oral fluids in group C was shorter than in groups A and B (group A 4.79 ± 1.28; group B 4.67 ± 1.11; group C 2.62 ± 0.64; p<0.001). The days of prior solid diet was less in group C than in groups A and B (group A 7.22 ± 3.87; group B 7.08 ± 3.18; group C 5.75 ± 1.70; p=0.027). The postoperative length of stay (LOS) was less in group C compared with that in groups A and B (group A 9.46 ± 4.84 days; group B 9.52 ± 7.45 days; group C 7.20 ± 2.37 days; p=0.023). The visual analog scale (VAS) scores on day 0, 1, and 2 in groups B and C were lower than those in group A (day 0, p<0.001; day 1, p<0.001; day 2, p=0.002), while the VAS score on day 3 showed no differences in the three groups (group A 1.29 ± 1.38; group B 0.98 ± 1.24; group C 0.75 ± 0.64, p=0.018). CONCLUSION: The findings suggest that SILS combined with ERAS may be a feasible and safe procedure for CRC surgery because it provides favorable cosmetic results, early dietary resumption, shorter hospital stays, and appropriate control of postoperative pain without increases in complications or readmission rates compared to conventional perioperative care with SILS or conventional laparoscopic surgery(CLS) of CRC. Further prospective randomized controlled studies are needed to enhance evidence-based medical evidence.

Short-Term Outcomes of Single-Incision Laparoscopic Surgery for Colorectal Cancer: A Single-Center, Open-Label, Non-Inferiority, Randomized Clinical Trial.

OBJECTIVE: To date, well-designed randomized controlled trials examining the safety, efficacy, and long-term outcomes of single-incision laparoscopic surgery (SILS) for colorectal cancer are scarce. The aim of the current study was to compare short-term outcomes of SILS for colorectal cancer with conventional laparoscopic surgery (CLS). METHODS: Between June 28, 2017, and June 29, 2019, a single-center, open-label, non-inferiority, randomized clinical trial was conducted at the Department of General Surgery, Ruijin Hospital (North), Shanghai Jiaotong University School of Medicine in Shanghai, China. In total, 200 patients diagnosed or suspected of colorectal cancer (cT1-4aN0-2M0) were randomly assigned to either the SILS or CLS group in a 1:1 ratio. The primary outcome was early morbidity rate. Secondary outcomes included intraoperative outcomes, pain intensity, postoperative recovery, pathologic outcomes, and long-term outcomes. RESULTS: In total, 193 participants (SILS, 97; CLS, 96) were analyzed in the modified intention-to-treat (MITT) population. Among them, 48 underwent right hemicolectomy (SILS n = 23, 23.7% and MLS n = 25, 26%), 15 underwent left hemicolectomy (SILS n = 6, 6.2% and MLS n = 9, 9.4%), 1 underwent transverse colectomy (MLS n = 1, 1%), 57 underwent sigmoidectomy (SILS n = 32, 33% and MLS n = 25, 26%), and 72 underwent anterior resection (SILS n = 36, 37.1% and MLS n = 36, 37.5%). No significant differences were observed in the baseline characteristics. The intraoperative complication was comparable between the two groups [5 (5.2%) vs. 4 (4.2%); difference, 1%; 95% CI, -5.8% to 7.8%; p > 0.999) and so was postoperative complication rates [10 (10.3%) vs. 14 (14.6%); difference, -4.3%; 95% CI, -13.9% to 5.3%; p = 0.392]. The SILS group showed shorter incision length [median (IQR), 4 (3.5-5) vs. 6.6 (6-7.5), p < 0.001] and lower VAS scores on the first [median (IQR), 4 (3-5) vs. 4 (4-5), p = 0.002] and the second day [median (IQR), 2 (1.5-3) vs. 3 (2-4), p < 0.001] after surgery. No statistically significant difference was found in other measured outcomes. CONCLUSIONS: Compared with CLS, SILS performed by experienced surgeons for selected colorectal cancer patients is non-inferior with good short-term safety and has the advantage of reducing postoperative pain. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT03151733.

Exosomal miR-200c-3p negatively regulates the migraion and invasion of lipopolysaccharide (LPS)-stimulated colorectal cancer (CRC).

BACKGROUND: Colorectal cancer (CRC) is a leading cancer and a major cause of death. Lipopolysaccharide (LPS), an abundant component in gut microbiome, is involved in CRC progression and metastasis, potentially through regulating the miRNA composition of CRC-derived exosomes. In this study, we aimed to identify miRNA species in exosome which regulates CRC progression after LPS stimulation. RESULTS: Firstly, we discovered a shift of miRNA profile in CRC exosome after LPS stimulation. Among the differentially expressed miRNAs, we identified miR-200c-3p as a potential key regulator of CRC progression and metastasis. Retrospective analysis revealed that miR-200c-3p was elevated in CRC tumor tissues, but decreased in the serum exosome in CRC patients. In vitro experiments demonstrated that exosomal miR-200c-3p expression did not influence CRC cell proliferation, but negatively regulated their capacity of migration and invasion in the presence of LPS. miR-200c-3p level in exosome influenced exosomal expression of Zinc finger E-box-binding homeobox-1 (ZEB-1) mRNA, one of the miR-200c targets which affects migration and invasion capacity, and further altered ZEB-1 protein expression in CRC cell. In addition, exosomal miR-200c-3p promotes apoptosis of HCT-116 cells. CONCLUSIONS: Our findings indicate that exosomal miR-200c-3p inhibits CRC migration and invasion, and promotes their apoptosis after LPS stimulation. It is suggested as a potential diagnostic marker and therapeutic target of CRC.

Multitarget stool DNA test compared with fecal occult blood test for colorectal cancer screening.

Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I-III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.

Asymmetrical degenerative marrow (Modic) changes in cervical spine: prevalence, correlative factors, and surgical outcomes.

BACKGROUND: The current study aimed to discuss the prevalence and surgical outcomes of the asymmetrical Modic changes and identify its correlative factors by multivariate logistic regression analysis. METHODS: Two hundred seventy-eight patients with single-level Modic changes and nerve compression symptoms were reviewed retrospectively from January 2008 to January 2015. 1.5-T MRI was performed to determine the Modic changes. Multivariate logistic regression analysis was used to identify the correlative factors of asymmetrical Modic changes. Surgeries were performed according to the surgical indications. The outcomes were recorded by Japanese Orthopaedic Association (JOA) score, Neck Disability Index (NDI) score, and recovery rate. RESULTS: Asymmetrical Modic changes were observed in 76 patients (27.34%) with 4 type 1, 69 type 2, and 3 type 3. C5/6 was the most frequently affected segment with 39 patients showing signal changes on MRI. Statistically significant difference was showed in conservative rehabilitation rate between two groups (p = 0.043). Multiple logistic regression analysis identified disc herniation and neurological symptoms as correlative factors of asymmetrical Modic changes, and the adjusted odds ratios (95% CI) were 2.079 (1.348-3.208) and 0.231 (0.143-0.373) respectively. No statistically significant difference was found in JOA scores and NDI scores between the two kinds of Modic changes. CONCLUSIONS: C5/6 was the most commonly affected level by Modic changes. Disc herniation and nerve root compression symptom were more closely correlated with asymmetrical Modic changes than conventional Modic changes. Asymmetrical Modic changes indicated poor result in conservative treatment; however, the final operation rate was similar between the two kinds of Modic changes. The outcomes of surgical treatment were satisfactory both in patients with asymmetrical Modic changes and conventional Modic changes.