Network Analysis of Osteoarthritis Progression Using a Steiner Minimal Tree Algorithm.

Purpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm. Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results. Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage. Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.

Neoadjuvant Chemotherapy With Oxaliplatin and Fluoropyrimidine Versus Upfront Surgery for Locally Advanced Colon Cancer: The Randomized, Phase III OPTICAL Trial.

PURPOSE: The role of neoadjuvant chemotherapy (NAC) in colon cancer remains unclear. This trial investigated whether 3 months of modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) or capecitabine and oxaliplatin (CAPOX) as NAC could improve outcomes in patients with locally advanced colon cancer versus upfront surgery. PATIENTS AND METHODS: OPTICAL was a randomized, phase III trial in patients with clinically staged locally advanced colon cancer (T3 with extramural spread into the mesocolic fat ≥5 mm or T4). Patients were randomly assigned 1:1 to receive six preoperative cycles of mFOLFOX6 or four cycles of CAPOX, followed by surgery and adjuvant chemotherapy (NAC group), or immediate surgery and the physician's choice of adjuvant chemotherapy (upfront surgery group). The primary end point was 3-year disease-free survival (DFS) assessed in the modified intention-to-treat (mITT) population. RESULTS: Between January 2016 and April 2021, of the 752 patients enrolled, 744 patients were included in the mITT analysis (371 in the NAC group; 373 in the upfront surgery group). At a median follow-up of 48.0 months (IQR, 46.0-50.1), 3-year DFS rates were 82.1% in the NAC group and 77.5% in the upfront surgery group (stratified hazard ratio [HR], 0.74 [95% CI, 0.54 to 1.03]). The R0 resection was achieved in 98% of patients who underwent surgery in both groups. Compared with upfront surgery, NAC resulted in a 7% pathologic complete response rate (pCR), significantly lower rates of advanced tumor staging (pT3-4: 77% v 94%), lymph node metastasis (pN1-2: 31% v 46%), and potentially improved overall survival (stratified HR, 0.44 [95% CI, 0.25 to 0.77]). CONCLUSION: NAC with mFOLFOX6 or CAPOX did not show a significant DFS benefit. However, this neoadjuvant approach was safe, resulted in substantial pathologic downstaging, and appears to be a viable therapeutic option for locally advanced colon cancer.

KAT2A Promotes the Succinylation of PKM2 to Inhibit its Activity and Accelerate Glycolysis of Gastric Cancer.

Gastric cancer (GC) is one of the main causes of cancer-related death. Lysine acetyltransferases 2 A (KAT2A) is a succinyltransferase that plays an essential role in cancer development. The pyruvate kinase M2 (PKM2) is a glycolysis rate-limiting enzyme that mediates the glycolysis of cancers. This study aimed to explore the effects and mechanism of KAT2A in GC progression. The effects of biological behaviors of GC cells were evaluated by MTT, colony formation and seahorse assays. The succinylation modification was assessed by immunoprecipitation (IP). The interaction between proteins were detected by Co-IP and immunofluorescence. A pyruvate kinase activity detection kit was used to evaluate the activity of PKM2. Western blot was performed to detect the expression and oligomerization of protein. Herein, we confirmed that KAT2A was highly expressed in GC tissues and was associated with a poor prognosis. Function studies showed that knockdown of KAT2A inhibited cell proliferation and glycolytic metabolism of GC. Mechanistically, KAT2A could directly interacted with PKM2 and KAT2A silencing inhibited the succinylation of PKM2 at K475 site. In addition, the succinylation of PKM2 altered its activity rather than its protein levels. Rescue experiments showed that KAT2A promoted GC cell growth, glycolysis, and tumor growth by promoting PKM2 K475 succinylation. Taken together, KAT2A promotes the succinylation of PKM2 at K475 to inhibit PKM2 activity, thus promotes the progression of GC. Therefore, targeting KATA2 and PKM2 may provide novel strategies for the treatment of GC.

Alisertib exerts KRAS allele­specific anticancer effects on colorectal cancer cell lines.

The aim of the present study was to examine the effects of alisertib (ALS) on RAS signaling pathways against a panel of colorectal cancer (CRC) cell lines and engineered Flp-In stable cell lines expressing different Kirsten rat sarcoma virus (KRAS) mutants. The viability of Caco-2KRAS wild-type, Colo-678KRAS G12D, SK-CO-1KRAS G12V, HCT116KRAS G13D, CCCL-18KRAS A146T and HT29BRAF V600E cells was examined by Cell Titer-Glo assay, and that of stable cell lines was monitored by IncuCyte. The expression levels of phosphorylated (p-)Akt and p-Erk as RAS signal outputs were measured by western blotting. The results suggested that ALS exhibited different inhibitory effects on cell viability and different regulatory effects on guanosine triphosphate (GTP)-bound RAS in CRC cell lines. ALS also exhibited various regulatory effects on the PI3K/Akt and mitogen-activated protein kinase (MAPK) pathways, the two dominant RAS signaling pathways, and induced apoptosis and autophagy in a RAS allele-specific manner. Combined treatment with ALS and selumetinib enhanced the regulatory effects of ALS on apoptosis and autophagy in CRC cell lines in a RAS allele-specific manner. Notably, combined treatment exhibited a synergistic inhibitory effect on cell proliferation in Flp-In stable cell lines. The results of the present study suggested that ALS differentially regulates RAS signaling pathways. The combined approach of ALS and a MEK inhibitor may represent a new therapeutic strategy for precision therapy for CRC in a KRAS allele-specific manner; however, this effect requires further study in vivo.

RAFF-Net: An improved tongue segmentation algorithm based on residual attention network and multiscale feature fusion.

Objective: Due to the complexity of face images, tongue segmentation is susceptible to interference from uneven tongue texture, lips and face, resulting in traditional methods failing to segment the tongue accurately. To address this problem, RAFF-Net, an automatic tongue region segmentation network based on residual attention network and multiscale feature fusion, was proposed. It aims to improve tongue segmentation accuracy and achieve end-to-end automated segmentation. Methods: Based on the UNet backbone network, different numbers of ResBlocks combined with the Squeeze-and-Excitation (SE) block was used as an encoder to extract image layered features. The decoder structure of UNet was simplified and the number of parameters of the network model was reduced. Meanwhile, the multiscale feature fusion module was designed to optimize the network parameters by combining a custom loss function instead of the common cross-entropy loss function to further improve the detection accuracy. Results: The RAFF-Net network structure achieved Mean Intersection over Union (MIoU) and F1-score of 97.85% and 97.73%, respectively, which improved 0.56% and 0.46%, respectively, compared with the original UNet; ablation experiments demonstrated that the improved algorithm could contribute to the enhancement of tongue segmentation effect. Conclusion: This study combined the residual attention network with multiscale feature fusion to effectively improve the segmentation accuracy of the tongue region, and optimized the input and output of the UNet network using different numbers of ResBlocks, SE block, multiscale feature fusion and weighted loss function, increased the stability of the network and improved the overall effect of the network.

Information Extraction from the Text Data on Traditional Chinese Medicine: A Review on Tasks, Challenges, and Methods from 2010 to 2021.

Background: The practice of traditional Chinese medicine (TCM) began several thousand years ago, and the knowledge of practitioners is recorded in paper and electronic versions of case notes, manuscripts, and books in multiple languages. Developing a method of information extraction (IE) from these sources to generate a cohesive data set would be a great contribution to the medical field. The goal of this study was to perform a systematic review of the status of IE from TCM sources over the last 10 years. Methods: We conducted a search of four literature databases for articles published from 2010 to 2021 that focused on the use of natural language processing (NLP) methods to extract information from unstructured TCM text data. Two reviewers and one adjudicator contributed to article search, article selection, data extraction, and synthesis processes. Results: We retrieved 1234 records, 49 of which met our inclusion criteria. We used the articles to (i) assess the key tasks of IE in the TCM domain, (ii) summarize the challenges to extracting information from TCM text data, and (iii) identify effective frameworks, models, and key findings of TCM IE through classification. Conclusions: Our analysis showed that IE from TCM text data has improved over the past decade. However, the extraction of TCM text still faces some challenges involving the lack of gold standard corpora, nonstandardized expressions, and multiple types of relations. In the future, IE work should be promoted by extracting more existing entities and relations, constructing gold standard data sets, and exploring IE methods based on a small amount of labeled data. Furthermore, fine-grained and interpretable IE technologies are necessary for further exploration.

Publication Trends in Rehabilitative Effects of Acupuncture: A Visual Analysis of the Literature.

Objectives: To conduct a comprehensive analysis of scientific outputs in 2011-2021 regarding the rehabilitative effects of acupuncture on diseases. Methods: The study was conducted in the form of knowledge graph and data visualization, with data being drawn from the Web of Science Core Collection database. Results: Articles and reviews were the dominant types; China, Guangzhou University of Chinese Medicine and Medicine ranked was the active country, institution, and journal, respectively, in terms of issued articles. Systematic reviews and the meta-analyses of stroke and pain were extensively carried out in the past decade, whose principal interventions were manual acupuncture, electroacupuncture, scalp acupuncture, and dry needling correspondingly at Baihui (DU20) and Zusanli (ST36). And most frequently utilized rehabilitation assessment criteria were the Fugl-Meyer Assessment Scale and the Barthel Index. More recently, motor function and chronic obstructive pulmonary disease have captured researchers' attention, which might be the futuristic frontier. Conclusions: This article provided a relatively panoramic picture of the scientific outputs in acupuncture for disease rehabilitation, which may help readers embrace the heated topic and grasp the recent research focus on this field.

A Traditional Chinese Medicine Syndrome Classification Model Based on Cross-Feature Generation by Convolution Neural Network: Model Development and Validation.

BACKGROUND: Nowadays, intelligent medicine is gaining widespread attention, and great progress has been made in Western medicine with the help of artificial intelligence to assist in decision making. Compared with Western medicine, traditional Chinese medicine (TCM) involves selecting the specific treatment method, prescription, and medication based on the dialectical results of each patient's symptoms. For this reason, the development of a TCM-assisted decision-making system has lagged. Treatment based on syndrome differentiation is the core of TCM treatment; TCM doctors can dialectically classify diseases according to patients' symptoms and optimize treatment in time. Therefore, the essence of a TCM-assisted decision-making system is a TCM intelligent, dialectical algorithm. Symptoms stored in electronic medical records are mostly associated with patients' diseases; however, symptoms of TCM are mostly subjectively identified. In general electronic medical records, there are many missing values. TCM medical records, in which symptoms tend to cause high-dimensional sparse data, reduce algorithm accuracy. OBJECTIVE: This study aims to construct an algorithm model compatible for the multidimensional, highly sparse, and multiclassification task of TCM syndrome differentiation, so that it can be effectively applied to the intelligent dialectic of different diseases. METHODS: The relevant terms in electronic medical records were standardized with respect to symptoms and evidence-based criteria of TCM. We structuralized case data based on the classification of different symptoms and physical signs according to the 4 diagnostic examinations in TCM diagnosis. A novel cross-feature generation by convolution neural network model performed evidence-based recommendations based on the input embedded, structured medical record data. RESULTS: The data set included 5273 real dysmenorrhea cases from the Sichuan TCM big data management platform and the Chinese literature database, which were embedded into 60 fields after being structured and standardized. The training set and test set were randomly constructed in a ratio of 3:1. For the classification of different syndrome types, compared with 6 traditional, intelligent dialectical models and 3 click-through-rate models, the new model showed a good generalization ability and good classification effect. The comprehensive accuracy rate reached 96.21%. CONCLUSIONS: The main contribution of this study is the construction of a new intelligent dialectical model combining the characteristics of TCM by treating intelligent dialectics as a high-dimensional sparse vector classification task. Owing to the standardization of the input symptoms, all the common symptoms of TCM are covered, and the model can differentiate the symptoms with a variety of missing values. Therefore, with the continuous improvement of disease data sets, this model has the potential to be applied to the dialectical classification of different diseases in TCM.

PRRX1 promotes colorectal cancer stemness and chemoresistance via the JAK2/STAT3 axis by targeting IL-6.

Background: Stemness acquirement is one of the hallmarks of cancer and the major reason for the chemoresistance and poor prognosis of colorectal cancer (CRC). Previous research has revealed the stimulatory role of paired related homeobox 1 (PRRX1) on CRC metastasis. However, the role of PRRX1 in stemness acquirement and chemoresistance of CRC is still not clear. Methods: A retrospective cohort study was performed to investigate the relationship between PRRX1 expression and multiple clinicopathological characteristics of CRC patients. The functional effects of PRRX1 on stemness and chemoresistance of CRC cells were validated by in vitro and in vivo assays. Gene set enrichment analysis (GSEA) and JASPAR software were performed to predict the underlying mechanisms. Enzyme-linked immunosorbent assay (ELISA), Western blot, immunofluorescence, and dual-luciferase reporter assays were used to confirm the PRRX1-mediated signaling and its downstream factors. Results: The expression of PRRX1 was up-regulated in CRC tissues and cell lines compared to normal epithelial tissues and cell lines. High expression of PRRX1 was tightly associated with the metastasis, chemoresistance, and poor prognosis of CRC patients. Additionally, PRRX1 significantly promoted the proliferation, viability, stemness, and chemoresistance of CRC cells, as well as the activation of the interleukin-6 (IL-6)/JAK2/STAT3 axis. Inhibiting the expression of IL-6 dramatically eliminated the effects of PRRX1 on CRC cell stemness and chemoresistance. Conclusions: PRRX1 plays a vital role in the stemness and chemoresistance of CRC cells via JAK2/STAT3 signaling by targeting IL-6. Further, PRRX1 may be a valid biomarker for predicting the effect of chemotherapy and prognosis of CRC patients.

Selenium nanoparticles coated with pH responsive silk fibroin complex for fingolimod release and enhanced targeting in thyroid cancer.

Cancer-targeted drug delivery systems based on nanoparticles (NPs) have been considered promising therapies. In this study, we developed a pH-responsive smart NPs drug delivery system using silk fibroin (SF), selenium nanoparticles (Se NPs), fingolimod (FTY720), and heptapeptide (T7). The prepared FTY720@T7-SF-Se NPs were spheres with an average diameter of 120 nm, which would contribute to the enhanced permeability and retention effects in tumour regions. The encapsulation efficiency (EE) of the FTY720@T7-SF-Se NPs was 71.95 ± 3.81%. The release of FTY720 from the nanocarriers was pH-dependent, and the release of FTY720 was accelerated in an acidic environment. Both in vitro and in vivo studies showed that FTY720@T7-SF-Se NPs had an enhanced cellular uptake selectivity and antitumor activity for thyroid cancer. The bio-distribution study in vivo further demonstrated that FTY720@T7-SF-Se NPs could effectively accumulate in the tumour region, thereby enhancing the ability to kill cancer cells in vivo. In addition, studies of histology and immunohistochemistry showed that FTY720@T7-SF-Se NPs had low toxicity to the major organs of tumour-bearing mice, indicating the prepared NPs has good biocompatibility in vivo. These results suggest that the tumour-targeted NPs delivery system (FTY720@T7-SF-Se NPs) has great potential as a new tool for thyroid cancer therapy.

Pattern of COVID-19 in Sichuan province, China: A descriptive epidemiological analysis.

This study described the epidemiology of 487 confirmed coronavirus disease 2019 (COVID-19) cases in Sichuan province of China, and aimed to provide epidemiological evidence to support public health decision making. Epidemiological information of 487 COVID-19 cases were collected from the official websites of 21 districts (including 18 cities, 3 autonomous prefecture) health commissions within Sichuan between 21st of January 2020 to 17th of April 2020. We focus on the single-day diagnosis, demographics (gender and age), regional distribution, incubation period and symptoms. The number of single-day confirmed COVID-19 cases reach a peak on January 29 (33 cases), and then decreased. Chengdu (121 cases), Dazhou (39 cases) Nanchong (37 cases) and Ganzi Tibetan Autonomous Prefecture (78 cases) contributed 275 cases (56.5% of the total cases) of Sichuan province. The median age of patients was 44.0 years old and 52.6% were male. The history of living in or visiting Hubei, close contact, imported and unknown were 170 cases (34.9%), 136 cases (27.9%), 21 cases (4.3%) and 160 cases (32.9%) respectively. The interval from the onset of initial symptoms to laboratory diagnosis was 4.0 days in local cases, while that of imported cases was 4.5 days. The most common symptoms of illness onset were fever (71.9%) and cough (35.9%). The growth rate of COVID-19 in Sichuan has significantly decreased. New infected cases have shifted from the living in or visiting Wuhan and close contact to imported. It is necessary to closely monitor the physical condition of imported cases.

[Therapeutic effect of laparoscopic Roux-en-Y gastric bypass in non-obese patients with type 2 diabetes].

OBJECTIVE: To evaluate the effectiveness of laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery for treatment of type 2 diabetes (T2D) in patients with a body mass index (BMI) < 27.5 kg/m2. METHODS: We retrospectively analyzed the data of patients who underwent LRYGB surgery from March, 2012 to June, 2018 in the General Hospital of Guangzhou Military Command and Jinshazhou Hospital of Guangzhou University of Chinese Medicine. The changes in the parameters of glucose metabolism and physical indicators of the patients in the first, second and third years after the surgery were analyzed in patients in low BMI group and high BMI group. RESULTS: All the 74 patients underwent LRYGB successfully without conversion to open surgery. One year after the surgery, fasting blood glucose (FBG), HbA1c, postprandial blood glucose, fasting insulin, HOMA-IR, fasting C-peptide, BMI, body weight and waistline were significantly improved compared with their preoperative values in low BMI group (P < 0.05). At 2 years after the operation, FBG, HbA1c, postprandial blood glucose, HOMA-IR, BMI, body weight and waistline were significantly improved compared with the preoperative values in low BMI group (P < 0.05). In the third year, FBG, HOMA-IR, fasting C-peptide, body weight and waistline were significantly improved compared with the preoperative values in low BMI group (P < 0.05). There was no significant difference in the parameters of glucose metabolism and islet function between low BMI group and high BMI group at different stages. No serious complications occurred in these patients after the surgery. CONCLUSIONS: LRYGB is effective for treatment of T2D in Chinese patients with a BMI < 27.5. After the surgery, the patient show reduced waistline without significant weight loss. The long-term results of the surgery still require further investigations with a larger samples and longer follow-up.

Ethanol promotes alcohol-related colorectal cancer metastasis via the TGF-ß/RUNX3/Snail axis by inducing TGF-ß1 upregulation and RUNX3 cytoplasmic mislocalization.

BACKGROUND: Alcohol intake is a well-known lifestyle risk factor for CRC, and an increasing number of studies have revealed that alcohol intake is also tightly associated with CRC metastasis. However, the effect of alcohol on CRC metastasis and its underlying mechanism remain unclear. METHODS: A retrospective cohort study was performed to investigate the characteristics of patients with alcohol-related CRC. The effects of ethanol on the biological behaviours of CRC cells were assessed through in vivo and in vitro assays using the Lieber-DeCarli ethanol liquid diet and ethanol, respectively. The ethanol-mediated signalling pathway and downstream factors were screened through ELISA, western blot, immunofluorescence and co-immunoprecipitation. FINDINGS: Most patients with alcohol-related CRC, particularly those with tumour metastasis, were characterized by a notably higher circulating ethanol level and a lower systemic acetaldehyde level. Moreover, CRC cells accumulated in ethanol, but not acetaldehyde, to notably higher levels compared with adjacent normal cells. Alcohol intake significantly promoted CRC metastasis via the ethanol-mediated TGF-ß/Smad/Snail axis, and ethanol induced the cytoplasmic mislocalization of RUNX3 and further promoted the aggressiveness of CRC by targeting Snail. Pirfenidone (PFD) significantly eliminated the effects of ethanol on CRC metastasis by specifically blocking TGF-ß signalling. INTERPRETATION: Alcohol intake plays a vital role in CRC metastasis via the ethanol-mediated TGF-ß/RUNX3/Snail axis, and PFD might be a novel therapeutic management strategy for CRC.

Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial.

PURPOSE: In the multicenter, open-label, phase III FOWARC trial, modified infusional fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) plus radiotherapy resulted in a higher pathologic complete response rate than fluorouracil plus radiotherapy in Chinese patients with locally advanced rectal cancer. Here, we report the final results. METHODS: Adults ages 18 to 75 years with stage II/III rectal cancer were randomly assigned (1:1:1) to five cycles of infusional fluorouracil (leucovorin 400 mg/m2, fluorouracil 400 mg/m2, and fluorouracil 2.4 g/m2 over 48 hours) plus radiotherapy (46.0 to 50.4 Gy delivered in 23 to 25 fractions during cycles 2 to 4) followed by surgery and seven cycles of infusional fluorouracil, the same treatment plus intravenous oxaliplatin 85 mg/m2 on day 1 of each cycle (mFOLFOX6), or four to six cycles of mFOLFOX6 followed by surgery and six to eight cycles of mFOLFOX6. The primary end point was 3-year disease-free survival (DFS). RESULTS: In total, 495 patients were randomly assigned to treatment. After a median follow-up of 45.2 months, DFS events were reported in 46, 39, and 46 patients in the fluorouracil plus radiotherapy, mFOLFOX6 plus radiotherapy, and mFOLFOX6 arms. In each arm, the probability of 3-year DFS was 72.9%, 77.2%, and 73.5% (P = .709 by the log-rank test), the 3-year probability of local recurrence after R0/1 resection was 8.0%, 7.0%, and 8.3% (P = .873 by the log-rank test), and the 3-year overall survival rate was 91.3%, 89.1%, and 90.7% (P = .971 by log-rank test), respectively. CONCLUSION: mFOLFOX6, with or without radiation, did not significantly improve 3-year DFS versus fluorouracil with radiation in patients with locally advanced rectal cancer. No significant difference in outcomes was found between mFOLFOX6 without radiotherapy and fluorouracil with radiotherapy, which requires additional investigation of the role of radiotherapy in these regimens.

[ADAM17 knockdown increases sensitivity of SW480 cells to cetuximad].

OBJECTIVE: To explore the association between expression of ADAM17 and cetuximad resistance in human colorectal cancer SW480 cells. METHODS: The expression of ADAM17 was detected using Western blotting in different human colorectal cancer cell lines, and the cells highly expressing ADAM17 were selected as the target cells. SW480 cells were transfected with ADAM17-siRNA 1 and ADAM17-siRNA 2 and the changes in the expression of ADAM17 protein were detected using Western blotting. SW480 cells were exposed to cetuximad for 24 h and the cell apoptosis was analyzed using flow cytometry. Transwell assay was used to examine the migration ability of SW480 cells with different expression levels of ADAM17; Western blotting was used to analyze the changes in the expressions of AKT signaling pathway-related proteins in the treated cells. RESULTS: The baseline expressions of ADAM17 were significantly higher in SW480 cells than in the other human colorectal cancer cell lines tested (P < 0.05). Both ADAM17-siRNA 1 and 2 effectively reduced the expression of ADAM17 protein in SW480 cells. Knockdown of ADAM17 with siRNA 1 significantly increased the sensitivity of SW480 cells to tocetuximad (P < 0.05), obviously inhibited the cell proliferation, migration and invasion, and significantly reduced the expressions of p-EGFR and p-AKT in the cells (P < 0.001). CONCLUSIONS: ADAM17 knockdown obviously inhibits EGFR-AKT signaling pathway and increases the sensitivity of SW480 cells to tocetuximad.

MicroRNA-661 expression is upregulated in pancreatic ductal adenocarcinoma and promotes cell proliferation.

Deregulation of microRNA (miRNA/miR) expression has been implicated in the development of pancreatic ductal adenocarcinoma (PDAC). However, the role of miR-661 in PDAC remains unknown. In the present study, it was revealed that miR-661 expression was significantly upregulated in PDAC tissues compared with that in adjacent normal tissues by using reverse transcription-quantitative polymerase chain reaction assays. Higher miR-661 expression revealed a positive association with lymph node metastasis, an advanced T stage and a poor prognosis in patients with PDAC. Furthermore, ectopic expression of miR-661 significantly promoted the cell proliferation ability in PDAC cell lines, and simultaneously promoted Wnt signaling pathway-related protein expression of ß-catenin, transcription factor 4 and cyclin D1 in vitro. However, the downregulation of miR-661 revealed reverse effects. Thus, the results of the present study indicated that miR-661 may function as a prognostic marker and provide insight for pancreatic cancer treatment.

[Structural changes of gut microbiota after gastric bypass in obese patients with type 2 diabetes].

OBJECTIVE: To investigate the structural changes inintestinal flora and metabolic changes in type 2 diabetic patients with obesity(BMI≥40 kg/m2)by sequencing the 16S rRNA genes. METHODS: Stool samples were collected from 4 diabetic patients before and after gastric bypass surgery for extraction of the total DNA. The diversity of the intestinal flora in the samples was investigated by 16S rRNA sequencing. After surgery, the changes in glucose and lipid metabolism were evaluated in the patients, and the changesin body mass index (BMI) and waist to hip ratio were assessed at 3 month intervals. RESULTS: After gastric bypass, the patient's BMI, waist to hip ratio, glucose metabolism and lipid metabolism gradually recovered the normal levels. The proportion of Bacteroidetesis increased and the proportions of Firmicutes and Proteobacteria decreased in the intestinal bacteria after the surgery. CONCLUSION: Gastric bypass surgery can effectively alleviate the condition of obese patients with type 2 diabetes and improve the composition of the intestinal flora.

[Efficacy of three-dimensional laparoscopic total thyroidectomy combined with central lymph node dissection for thyroid cancer and its effect on inflammatory responses of the patients].

OBJECTIVE: To analyze the effect of three-dimensional (3D) laparoscopic total thyroidectomy combined with central lymph node dissection for thyroid cancer and its effect on the inflammatory response of the patients. METHODS: The clinical data were analyzed in 90 patients with thyroid cancer undergoing radical thyroidectomy at our hospital between September, 2013 to April, 2016, including 30 receiving 3D laparoscopic surgeries, 30 with 2D laparoscopic surgeries and 30 with open surgeries. The surgical data, postoperative adverse reactions and the impact of the surgeries on the inflammatory responses of the patients were compared among the 3 groups. RESULTS: Compared with the open surgery and 2D laparoscopic surgery, 3D laparoscopic surgery was associated with lowered blood loss during the surgery and a lowered incidence of adverse reactions. The operation time in 3D group was significantly shorter than that in 2D group (P<0.05), but the total hospitalization expenses were similar between the two groups. The postoperative drainage volume did not differ significantly between the 3D group and the other two groups. The postoperative hospital stay, number of lymph nodes dissected, positivity rate of lymph nodes and the inflammatory response showed no significant differences among the 3 groups (P>0.05). CONCLUSION: 3D laparoscopic total thyroidectomy combined with central lymph node dissection is safe and effective and reduces intraoperative blood loss and perioperative adverse reactions without significant influence on inflammatory response in patients with thyroid cancer.

Impact of platelet to lymphocyte ratio and metabolic syndrome on the prognosis of colorectal cancer patients.

OBJECTIVE: The aim of this study was to evaluate the prognostic value of both platelet to lymphocyte ratio (PLR) and metabolic syndrome (MetS) in colorectal cancer (CRC) patients. PATIENTS AND METHODS: We retrospectively enrolled 1,163 CRC patients. Preoperative values of PLR were stratified into three groups according to cut-off values of 120 and 220. The Kaplan-Meier analysis was used to calculate cumulative survival rate related to PLR and MetS. Cox proportional hazard regression models were used to analyze potential risk factors and the prognosis associated with PLR and MetS in CRC patients. RESULTS: PLR was significantly higher in the MetS(+) group as compared to MetS(-) group (P=0.039). An elevated PLR was significantly associated with mortality (P=0.014), but not the existence of MetS (P=0.235). In multivariate regression analysis, PLR was an independent risk factor for overall survival (OS) (P=0.046). For the subgroup with a PLR >220, MetS was an independent predictor for both OS and disease-free survival (P=0.039 and P=0.047, respectively) by multivariate analysis adjusting for confounding covariates. In addition, the presence of MetS was associated with a 2-fold increased risk of mortality and tumor recurrences (hazard ratio [HR] =2.0 and HR =1.9, P<0.05, respectively). CONCLUSION: Preoperative PLR was associated with MetS in CRC patients. Testing for the combined presence of PLR and MetS could potentially improve the predictive accuracy of CRC prognosis.