Predictive Value of Combined HbA1c and Neutrophil-to-Lymphocyte Ratio for Diabetic Peripheral Neuropathy in Type 2 Diabetes.

BACKGROUND Diabetic peripheral neuropathy (DPN) is a prevalent complication affecting over 60% of type 2 diabetes patients. Early diagnosis is challenging, leading to irreversible impacts on quality of life. This study explores the predictive value of combining HbA1c and Neutrophil-to-Lymphocyte Ratio (NLR) for early DPN detection. MATERIAL AND METHODS An observational study was conducted at the First People's Hospital of Linping District, Hangzhou spanning from May 2019 to July 2020. Data on sex, age, biochemical measurements were collected from electronic medical records and analyzed. Employing multivariate logistic regression analysis, we sought to comprehend the factors influencing the development of DPN. To assess the predictive value of individual and combined testing for DPN, a receiver operating characteristic (ROC) curve was plotted. The data analysis was executed using R software (Version: 4.1.0). RESULTS The univariate and multivariate logistic regression analysis identified the level of glycated hemoglobin (HbA1C) (OR=1.94, 95% CI: 1.27-3.14) and neutrophil-to-lymphocyte ratio (NLR) (OR=4.60, 95% CI: 1.15-22.62, P=0.04) as significant risk factors for the development of DPN. Receiver operating characteristic (ROC) curve analysis demonstrated that HbA1c, NLR, and their combined detection exhibited high sensitivity in predicting the development of DPN (71.60%, 90.00%, and 97.2%, respectively), with moderate specificity (63.8%, 45.00%, and 50.00%, respectively). The area under the curve (AUC) for these predictors was 0.703, 0.661, and 0.733, respectively. CONCLUSIONS HbA1c and NLR emerge as noteworthy risk indicators associated with the manifestation of DPN in patients with type 2 diabetes. The combined detection of HbA1c and NLR exhibits a heightened predictive value for the development of DPN.

TB-DROP: deep learning-based drug resistance prediction of Mycobacterium tuberculosis utilizing whole genome mutations.

The most widely practiced strategy for constructing the deep learning (DL) prediction model for drug resistance of Mycobacterium tuberculosis (MTB) involves the adoption of ready-made and state-of-the-art architectures usually proposed for non-biological problems. However, the ultimate goal is to construct a customized model for predicting the drug resistance of MTB and eventually for the biological phenotypes based on genotypes. Here, we constructed a DL training framework to standardize and modularize each step during the training process using the latest tensorflow 2 API. A systematic and comprehensive evaluation of each module in the three currently representative models, including Convolutional Neural Network, Denoising Autoencoder, and Wide & Deep, which were adopted by CNNGWP, DeepAMR, and WDNN, respectively, was performed in this framework regarding module contributions in order to assemble a novel model with proper dedicated modules. Based on the whole-genome level mutations, a de novo learning method was developed to overcome the intrinsic limitations of previous models that rely on known drug resistance-associated loci. A customized DL model with the multilayer perceptron architecture was constructed and achieved a competitive performance (the mean sensitivity and specificity were 0.90 and 0.87, respectively) compared to previous ones. The new model developed was applied in an end-to-end user-friendly graphical tool named TB-DROP (TuBerculosis Drug Resistance Optimal Prediction: https://github.com/nottwy/TB-DROP ), in which users only provide sequencing data and TB-DROP will complete analysis within several minutes for one sample. Our study contributes to both a new strategy of model construction and clinical application of deep learning-based drug-resistance prediction methods.

[Effect of proximal fibula osteotomy on tension of lateral knee soft tissue in patients with knee osteoarthritis].

OBJECTIVE: To evaluate the short-term efficacy of proximal fibula osteotomy in the treatment of knee osteoarthritis, and to analyze the effect of osteotomy on the tension of the lateral knee soft tissue of patients and verify the reliability of the Arch string theory. METHODS: A total of 71 patients with varus knee osteoarthritis from December 2019 to March 2022 were included, 3 patients dropped out, and 68 patients completed all trials, collected 27 males and 41 females, aged from 51 to 79 years old, with an average of (68.0±7.0 ) years old. The follow-up time ranged from 4 to 12 weeks, with an average of (3.76±1.94) weeks. After admission, the patient underwent Proximal fibula osteotomy, and the tension of lateral knee soft tissue, visual analogue scale (VAS) of pain, the western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and other indicators were recorded before surgery and 1 month after surgery in the weight-bearing state. RESULTS: According to the VAS, the curative effect of a single index was evaluated by referring to the score before and after treatment by Bao Zongzhao. Thirty seven cases were markedly effective, 27 cases were effective, and 4 cases were ineffective. After surgery, 3 patients presented with weakness of dorsalis pedis extension and 1 presented with paresthesia of dorsalis pedis, which disappeared after symptomatic treatment . The VAS and WOMAC score at 1 month after operation were lower than those before operation, and the differences were statistically significant(P<0.001). The tension of lateral knee soft tissue 1 month after operation was lower than that before operation, and the difference had statistical significance(P<0.001). CONCLUSION: Proximal fibula osteotomy is safe and effective in the treatment of varus knee osteoarthritis in the short term. One month after osteotomy, the tension of lateral knee soft tissue increases under weight-bearing state, but the long-term changes still need further observation and follow-up.

Prediction of adenocarcinoma and squamous carcinoma based on CT perfusion parameters of brain metastases from lung cancer: a pilot study.

Objectives: Predicting pathological types in patients with adenocarcinoma and squamous carcinoma using CT perfusion imaging parameters based on brain metastasis lesions from lung cancer. Methods: We retrospectively studied adenocarcinoma and squamous carcinoma patients with brain metastases who received treatment and had been pathologically tested in our hospital from 2019 to 2021. CT perfusion images of the brain were used to segment enhancing tumors and peritumoral edema and to extract CT perfusion parameters. The most relevant perfusion parameters were identified to classify the pathological types. Of the 45 patients in the study cohort (mean age 65.64 ± 10.08 years; M:F = 24:21), 16 were found to have squamous cell carcinoma. Twenty patients were with brain metastases only, and 25 patients were found to have multiple organ metastases in addition to brain metastases. After admission, all patients were subjected to the CT perfusion imaging examination. Differences in CT perfusion parameters between adenocarcinoma and squamous carcinoma were analyzed. The receiver operating characteristic (ROC) curves were used to predict the types of pathology of the patients. Results: Among the perfusion parameters, cerebral blood flow (CBF) and mean transit time (MTT) were significantly different between the two lung cancers (adenocarcinoma vs. squamous cell carcinoma: p < 0.001, p = 0.012.). Gender and tumor location were identified as the clinical predictive factors. For the classification of adenocarcinoma and squamous carcinoma, the model combined with CBF and clinical predictive factors showed better performance [area under the curve (AUC): 0.918, 95% confidence interval (CI): 0.797-0.979). The multiple organ metastasis model showed better performance than the brain metastasis alone model in subgroup analyses (AUC: 0.958, 95% CI: 0.794-0.999). Conclusion: CT perfusion parameter analysis of brain metastases in patients with primary lung cancer could be used to classify adenocarcinoma and squamous carcinoma.

Predictive Values of Blood Type I and Type II Interferon Production for Disease Activity and Clinical Response to TNF-α Blocking Therapy in Patients with Ankylosing Spondylitis.

Tumor necrosis factor-α (TNF-α) blocking therapy is recommended to treat ankylosing spondylitis for patients who fail to respond to nonsteroidal anti-inflammatory drugs (NSAIDs). Herein, we attempt to dissect whether blood type I and II interferon (IFN) production can be predictive of ankylosing spondylitis progression and treatment response to the tumor necrosis factor inhibitor (TNFi). A total of 50 ankylosing spondylitis patients receiving originator TNFi with a 6-month period were retrospectively analyzed. The patients who reached the Assessment of SpondyloArthritis international Society 40 (ASAS40) response at the 6-month interval were classified as responders (n = 29) to TNFi treatment, otherwise as non-responders (n = 21). The serum type I IFN activity, and the serum levels of IFN-α and IFN-γ in the patients at baseline were notably greater than the healthy controls. Pearson correlation analysis showed positive correlations in the patients between the serum type I IFN activity or the serum levels of IFN-α and IFN-γ, and BASDAI scores, ASDASCRP or pro-inflammatory factor production. The responders were demonstrated with reduced serum type I IFN activity concomitant with lower serum levels of IFN-α and IFN-γ compared to the non-responders after anti-TNF treatment. The serum type I IFN activity, and the serum levels of IFN-α and IFN-γ used as a test to predict responders and non-responders to anti-TNF treatment produced an area under the curve (AUC) of 0.837, 0.814, and 0.787, respectively. In conclusion, the study demonstrates that blood type I and II IFN production may be correlated with disease activity, inflammatory cytokine production, and indicative of unsatisfying response to TNFi treatment in ankylosing spondylitis patients.

Elevation and phylogeny shape herbaceous seed dormancy in a biodiversity hotspot of southwest China.

Seed dormancy contributes greatly to successful establishment and community stability and shows large variation over a continuous status scale in mountain ecosystems. Although empirical studies have shown that seed dormancy status (SDS) is shaped by elevation and phylogenetic history in mountain ecosystems, few studies have quantified their combined effects on SDS. Here, we collected mature seeds from 51 populations of 11 Impatiens species (Balsaminaceae) along an elevational gradient in the Gaoligong Mountains of southwest China and estimated SDS using mean dormancy percentage of fresh seeds germinated at three constant temperatures (15, 20, and 25°C). We downloaded 19 bioclimatic variables from WorldClim v.2.1 for each Impatiens population and used internal transcribed spacer (ITS), atpB-rbcL, and trnL-F molecular sequences from the GenBank nucleotide database to construct a phylogenetic tree of the 11 species of Impatiens. Logistic regression model analysis was performed to quantify the effects of phylogeny and environment on SDS. Results identified a significant phylogenetic SDS signal in the Impatiens species. Furthermore, elevation and phylogeny accounted for 63.629% of the total variation in SDS among the Impatiens populations. The best logistic model indicated that temperature was the main factor influencing variation in SDS among the Impatiens species, and model residuals were significantly correlated with phylogeny, but not with elevation. Our results indicated that seed dormancy is phylogenetically conserved, and climate drives elevational patterns of SDS variation in mountain ecosystems. This study provides new insights into the response of seed plant diversity to climate change.

Low-oxygen rare earth steels.

Rare earth (RE) addition to steels to produce RE steels has been widely applied when aiming to improve steel properties. However, RE steels have exhibited extremely variable mechanical performances, which has become a bottleneck in the past few decades for their production, utilization and related study. Here in this work, we discovered that the property variation of RE steels stems from the presence of oxygen-based inclusions. We proposed a dual low-oxygen technology, and keeping low levels of oxygen content in steel melts and particularly in the raw RE materials, which have long been ignored, to achieve impressively stable and favourable RE effects. The fatigue life is greatly improved by only parts-per-million-level RE addition, with a 40-fold improvement for the tension-compression fatigue life and a 40% enhancement of the rolling contact fatigue life. We find that RE appears to act by lowering the carbon diffusion rate and by retarding ferrite nucleation at the austenite grain boundaries. Our study reveals that only under very low-oxygen conditions can RE perform a vital role in purifying, modifying and micro-alloying steels, to improve the performance of RE steels.

Identification of region of difference and H37Rv-related deletion in Mycobacterium tuberculosis complex by structural variant detection and genome assembly.

Mycobacterium tuberculosis complex (MTBC), the main cause of TB in humans and animals, is an extreme example of genetic homogeneity, whereas it is still nevertheless separated into various lineages by numerous typing methods, which differ in phenotype, virulence, geographic distribution, and host preference. The large sequence polymorphism (LSP), incorporating region of difference (RD) and H37Rv-related deletion (RvD), is considered to be a powerful means of constructing phylogenetic relationships within MTBC. Although there have been many studies on LSP already, focusing on the distribution of RDs in MTBC and their impact on MTB phenotypes, a crumb of new lineages or sub-lineages have been excluded and RvDs have received less attention. We, therefore, sampled a dataset of 1,495 strains, containing 113 lineages from the laboratory collection, to screen for RDs and RvDs by structural variant detection and genome assembly, and examined the distribution of RvDs in MTBC, including RvD2, RvD5, and cobF region. Consistent with genealogical delineation by single nucleotide polymorphism (SNP), we identified 125 RDs and 5 RvDs at the species, lineage, or sub-lineage levels. The specificities of RDs and RvDs were further investigated in the remaining 10,218 strains, suggesting that most of them were highly specific to distinct phylogenetic groups, could be used as stable genetic markers in genotyping. More importantly, we identified 34 new lineage or evolutionary branch specific RDs and 2 RvDs, also demonstrated the distribution of known RDs and RvDs in MTBC. This study provides novel details about deletion events that have occurred in distinct phylogenetic groups and may help to understand the genealogical differentiation.

Drug resistance prediction and resistance genes identification in Mycobacterium tuberculosis based on a hierarchical attentive neural network utilizing genome-wide variants.

Prediction of antimicrobial resistance based on whole-genome sequencing data has attracted greater attention due to its rapidity and convenience. Numerous machine learning-based studies have used genetic variants to predict drug resistance in Mycobacterium tuberculosis (MTB), assuming that variants are homogeneous, and most of these studies, however, have ignored the essential correlation between variants and corresponding genes when encoding variants, and used a limited number of variants as prediction input. In this study, taking advantage of genome-wide variants for drug-resistance prediction and inspired by natural language processing, we summarize drug resistance prediction into document classification, in which variants are considered as words, mutated genes in an isolate as sentences, and an isolate as a document. We propose a novel hierarchical attentive neural network model (HANN) that helps discover drug resistance-related genes and variants and acquire more interpretable biological results. It captures the interaction among variants in a mutated gene as well as among mutated genes in an isolate. Our results show that for the four first-line drugs of isoniazid (INH), rifampicin (RIF), ethambutol (EMB) and pyrazinamide (PZA), the HANN achieves the optimal area under the ROC curve of 97.90, 99.05, 96.44 and 95.14% and the optimal sensitivity of 94.63, 96.31, 92.56 and 87.05%, respectively. In addition, without any domain knowledge, the model identifies drug resistance-related genes and variants consistent with those confirmed by previous studies, and more importantly, it discovers one more potential drug-resistance-related gene.

Hypoxia-induced FOXO4/LDHA axis modulates gastric cancer cell glycolysis and progression.

BACKGROUND AND AIM: We previously identified forkhead box (FOX) O4 mRNA as a predictor in gastric cancer (GC). However, the underlying mechanism has yet to be elucidated. We aimed to illustrate the mechanism by which FOXO4 regulated glycolysis under hypoxia in GC. METHODS: FOXO4 protein expression was investigated by immunohistochemical staining of 252 GC and their normal adjacent tissues. We restored or silenced FOXO4 expression in GC cell lines to explore the underlying mechanisms. RESULTS: FOXO4 was downregulated in GC. Loss of FOXO4 expression was validated in univariate and multivariate survival analysis as an independent prognostic predictor for overall survival (P < 0.05) and disease-free survival (P<0.05). Restored FOXO4 expression significantly impaired the glycolysis rate in GC cells, while silencing FOXO4 expression enhanced glycolysis rate. FOXO4 expression was inversely associated with maximum standardized uptake value in mice models and patient samples. Mechanistically, FOXO4 bound to the glycolytic enzyme lactate dehydrogenase (LDH)A promoter and inactivated its activity in a dose-dependent manner (P < 0.05). Finally, we determined that FOXO4 was a transcriptional target of hypoxia-inducible factor (HIF) -1α, which is central in response to hypoxia. CONCLUSIONS: Our data suggested that FOXO4 plays a key role in the regulation of glycolysis in GC, and disrupting the HIF-1α-FOXO4-LDHA axis might be a promising therapeutic strategy for GC.

Histone deacetylase-1 as a prognostic factor and mediator of gastric cancer progression by enhancing glycolysis.

Histone deacetylase 1 (HDAC1) has been shown to be closely associated with tumor development. We investigated its effects on survival and biological behavior in gastric cancer (GC). HDAC1 expression and glycolysis activity were analyzed in a cohort of 252 samples of primary GC tumors and in vitro study. High HDAC1 (HDAC1High) staining was seen in 60.7% patients with GCs, which was significantly greater than was seen in normal epithelial cells (19.4%; P < .005). HDAC1High expression was associated with larger tumor size (P = .001), advanced T stage (P = .001), lymph node metastases (N stage; P < .001), and lymphovascular invasion (P = .005). Univariate and multivariate survival analyses showed HDAC1 expression to be an independent prognostic factor for both disease-free survival and overall survival (P < .05). In vitro studies showed a notably decreased glycolysis rate in HDAC1 knockdown cells. In patients' samples, HDAC1High expression was always accompanied with high Maximal standardized uptake value (SUVmax) value (P < .05). A hypoxia-inducible factor (HIF)-1α response element-luciferase reporter system showed HDAC1 to affect HIF1α activity in a dose-dependent manner. In conclusion, HDAC1 promotes glycolysis in GC and affects HIF-1α activity in tumor progression and metastasis. HDAC1High expression was also an independent adverse prognostic factor for overall survival and disease-free survival.

Aldolase A as a prognostic factor and mediator of progression via inducing epithelial-mesenchymal transition in gastric cancer.

Glycolysis is regarded as the hallmark of cancer development and progression, which involves a multistep enzymatic reaction. This study aimed to explore the clinicopathological significance and potential role of glycolytic enzyme aldolase A (ALDOA) in the carcinogenesis and progression of gastric cancer (GC). ALDOA was screened from three paired liver metastasis tissues and primary GC tissues and further explored with clinical samples and in vitro studies. The ALDOA protein level significantly correlated with a larger tumor diameter (P = .004), advanced T stage (P < .001), N stage (P < .001) and lymphovascular invasion (P = .001). Moreover, the expression of ALDOA was an independent prognostic factor for the 5-year overall survival and disease-free survival of patients with GC in both univariate and multivariate survival analyses (P < .05). Silencing the expression of ALDOA in GC cell lines significantly impaired cell growth, proliferation and invasion ability (P < .05). Knockdown of the expression of ALDOA reversed the epithelial-mesenchymal transition process. Mechanically, ALDOA could affect the hypoxia-inducible factor (HIF)-1α activity as demonstrated by the HIF-1α response element-luciferase activity in GC cells. Collectively, this study revealed that ALDOA was a potential biomarker of GC prognosis and was important in the carcinogenesis and progression of human GC.

Diagnostic Accuracy of Magnifying Endoscopy with Narrow Band Imaging and Its Diagnostic Value for Invasion Depth Staging in Esophageal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND GOALS: This study aimed to investigate the diagnostic accuracy of magnifying endoscopy with narrow band imaging (ME-NBI) and determine its value for invasion depth staging in esophageal squamous cell carcinoma. METHODS: We searched the PubMed, Embase, and Cochrane Library databases and found relevant studies published up to December 2016. Quality Assessment of Diagnostic Accuracy Studies 2 was used to evaluate the quality of the studies. We calculated sensitivity, specificity, and positive and negative likelihood values from forest plots and determined summary receiver operating characteristic (sROC) curves for ME-NBI diagnostic accuracy analysis. RESULTS: Ten studies met our criteria and were selected for this meta-analysis. A total of 1,033 patients underwent ME-NBI, and 207 of these patients received a diagnosis of staging mucosal or submucosal invasion. The pooled sensitivity, specificity, and positive and negative likelihood values of ME-NBI for the diagnostic rate were 0.90 (95% CI, 0.71-0.97), 0.90 (95% CI, 0.80-0.95), 6.74 (95% CI, 3.52-712.89), and 0.20 (95% CI, 0.10-0.42), respectively. The area under the curve (AUC) was 0.95 for all studies. CONCLUSIONS: ME-NBI provides a high diagnostic rate in evaluating the esophagus to diagnose squamous cell carcinoma. In the differentiation for invasion depth staging, ME-NBI was demonstrated to be superior to white light endoscopy and had a similar diagnostic rate compared with HF-EUS. However, HF-EUS had high positive likelihood values for invasion depth staging, suggesting that HF-EUS is a reliable method for confirming invasion depth staging.

Decrease of γ-aminobutyric acid and zinc ions in the islet periportal circulation stimulates glucagon secretion during hypoglycemia.

The present study assessed the effects of γ-aminobutyric acid (GABA) from ß-cells on glucose levels and glucagon secretion, and identified channels via which glucagon secretion is initiated. An in vivo experiment was performed containing three groups: Intrapancreatic artery infusion of GABA alone, GABA plus insulin or insulin alone in rats with diabetes. Rats infused with GABA and insulin were also subdivided in groups receiving additional infusion of K+-channel activator diazoxide (DIA), K+-channel blocker tolbutamide (TLB) and calcium channel blocker nifedipine (NIF). In the hypoglycemic state, termination of infusion of insulin and insulin plus GABA resulted in signaling to the α-cells to secrete glycogen, while that of GABA alone did not. However, intrapancreatic artery infusion of K+-channel activator DIA, K+-channel blocker TLB or calcium channel blocker NIF in addition to GABA and insulin had no effect on glucagon secretion. In conclusion, if the delivery of insulin or GABA plus insulin in rats with hypoglycemia is terminated, ß-cells are stimulated and signal the α-cells to secrete glucagon. Thus, the detection of a sudden decrease in zinc levels by ß-cells as well as a decrease in GABA in the periportal circulation induces signaling to α-cells to stimulate them to secrete glucagon.

Endoscopic retrograde cholangiopancreatography versus laparoscopic exploration for common bile duct stones in post-cholecystectomy patients: a retrospective study.

BACKGROUND AND OBJECTIVE: Common bile duct (CBD) stones are common in patients even after cholecystectomy. Besides endoscopic retrograde cholangiography (ERCP), laparoscopic common bile duct exploration (LCBDE) is also applied. This study aims to compare clinical indications, therapeutic benefits and complications for these two managements. METHODS: From October 2012 to February 2015, 1072 consecutive patients were diagnosed as choledocholithiasis in our single hospital. Post-cholecystectomy patients who underwent ERCP or LCBDE were included. Clinical data were analyzed, such as success rate, complications, procedure duration, postoperative hospital stay, total cost and recurrence of ductal stones. Prior ERCP, previous biliary anatomic alteration surgeries and lost to follow up were the excluding criteria. RESULTS: 141 patients were included according to the criteria, and 87 cases underwent ERCP and 54 cases underwent LCBDE. Age and sex distribution of patients were comparable between the two groups. The success rate for CBD stones clearance was 97.7% in the ERCP group, compared with 87.0% in the LCBDE group (p=0.03). The mean procedure duration was also significantly shorter in ERCP group (52.0±15.8 vs. 102.9±40.1 min; p<0.001). Postoperative hospital stay was similar (5.5±2.6 vs. 5.9±2.3 days; p=0.40). And no significant difference for postoperative complications (3.4% vs. 11.1%; p=0.15), total cost ($3787.1±1061.5 vs. $3983.54±1257.1, p=0.32), and the rate of bile duct stones recurrence (6.9% vs. 7.4%, p=1.00). CONCLUSIONS: For clearing CBD stones in patients after cholecystectomy, ERCP was more efficient and might be the first choice, while LCBDE might be beneficial for patients with large stones.

Krüppel-Like Factor 7 is a Marker of Aggressive Gastric Cancer and Poor Prognosis.

BACKGROUND/AIMS: Krüppel-like factor (KLF) 7 protein is a member of the KLF transcription factor family, which plays important roles in regulating the expression of genes involved in cell growth, proliferation, differentiation and metabolism. However, the role of KLF7 in gastric cancer (GC) is unknown. The aim of this study is to explore the role of KLF7 in GC and its correlation with clinicopathological characteristics and prognosis of GC patients. METHODS: We first systematically evaluated dysregulation of the KLF family in The Cancer Genome Atlas (TCGA) GC database. Then, 252 patients who underwent surgery for GC were enrolled to validate the results from the TCGA. Functional studies were also used to explore the role of KLF7 in GC. RESULTS: In the TCGA database, we found that KLF7 was an independent predictor for survival by both univariate and multivariate analysis (P<0.05). In a validation cohort, KLF7 expression was significantly increased in GC tissues compared with adjacent normal controls (P=0.013). High KLF7 expression correlated with inferior prognostic factors, such as T stage (P=0.022), N stage (P =0.005) and lymphovascular invasion (P=0.009). Furthermore, we observed a strong negative correlation between KLF7 expression and 5-year overall survival and disease-free survival in GC patients (P<0.05). Moreover, our in vitro studies showed a notable decrease in migration in KLF7 knockdown cells. CONCLUSION: KLF7 has an important role in GC progression, as it inhibits GC cell migration and may serve as a prognostic marker.

Expression of PRR11 protein and its correlation with pancreatic cancer and effect on survival.

This study aimed at finding the relationship between the level of expression of the PRR11 protein in pancreatic carcinoma, and the clinical characteristics of the tumor. PCR technique was used to analyze the expression levels of the PRR11 gene in 38 samples from pancreatic cancer patients and 10 samples from normal pancreatic tissues. Western blot analysis and immunohistochemistry were used to measure the expression of the PRR11. Additionally, the migration ability of cancerous cells expressing PRR11 and those with inhibited expression were compared using a wound healing assay. Finally, the relationships between the expression level of PRR11 protein and variables such as tumor size, tumor invasion, TNM stages, and the overall survival time of patients with pancreatic cancer were calculated. Our results showed the expression level of the PRR11 gene in pancreatic cancer tissues was significantly higher than that in normal pancreatic tissues. The detection of PRR11 protein in cancer tissues versus normal tissues was 78.9 (30/38) vs. 0 (0/10), respectively. The western blot results confirmed this by showing a significantly higher level of expression of the PRR11 protein in pancreatic cancer tissues than in normal tissues (P<0.05). Inhibiting the expression of PRR11 in cancer cells reduced the migration ability of the cells. Finally, the expression of PRR11 was positively correlated with the invasion, disease and tissue differentiation stages of the pancreatic cancer. By comparing clinical data and expression patterns in patients, we found the survival rate in those expressing the PRR11 protein by immunohistochemistry to be lower than in those with tissues negative to the PRR11 protein. Our results show, the expression of PRR11 protein in pancreatic cancer is closely related to the development of the cancer and a poor prognosis. These findings provide a theoretical and experimental basis for approaching the diagnosis and treatment of pancreatic cancer using PRR11 as a molecular target.

Shen-Cao granules formulated based on traditional Chinese medicine alleviates bone marrow suppression caused by platinum-based anticancer reagents.

BACKGROUND: The aim of this study was to evaluate effects of Shen-Cao granules for the prevention of thrombocytopenia caused by anticancer chemotherapy. METHODS: In this prospective study, a total of 200 patients with various malignant tumors were enrolled and evenly divided into a Shen-Cao granule treatment (n = 100) and a control group (n = 100). After 2 cycles chemotherapy with any combination of platinum-based drugs (cisplatin, carboplatin, and nedaplatin), the blood platelet (PLT) counts, levels of the PLT production regulator thrombopoietin (TPO), PLT aggregation rates, and the PLT activation marker CD62P expressions were monitored for 2 weeks. RESULTS: During 2 weeks of post-chemotherapy, the mean values of the minimum PLT count were 49.65 ±â€Š7.35 × 10/L in the treatment group and 31.56 ±â€Š9.32 × 10/L in the control group. The PLT count in the treatment group reached the lowest value 1.8 days later and recovered to a concentration ≥100 × 10/L 3 days earlier than in the control group. The concentrations of the TPO were 71.43 ±â€Š1.74 and 87.24 ±â€Š0.92 ng/mL in the treatment group and 65.75 ±â€Š1.39 and 67.75 ±â€Š0.67 ng/mL in the control group at 7 and 14 days post-chemotherapy, respectively. The maximum PLT aggregation rate declined after chemotherapy in the treatment group from 58.14 ±â€Š11.46% to 52.89 ±â€Š10.52%, while it increased in the control group from 56.94 ±â€Š10.55% to 61.75 ±â€Š12.26%. Coordinately, the expression of CD62P in the treatment group decreased from 6.17 ±â€Š0.59% to 4.89 ±â€Š0.72%, while it increased from 6.09 ±â€Š0.75% to 7.75 ±â€Š0.67% in the control group. CONCLUSION: Our study demonstrated that Shen-Cao granule treatment alleviated thrombocytopenia after chemotherapy, and reduced tumor-induced PLT activation and aggregation.

RNA sequencing analysis reveals protective role of kruppel-like factor 3 in colorectal cancer.

The Kruppel-like factor (KLF) family of transcription factors plays an important role in embryonic formation and cancer progression. This study was performed to determine the clinical importance of the KLF family in colorectal cancer (CRC). In total, 361 patients with CRC from The Cancer Genome Atlas (TCGA) cohort were used to comprehensively study the role of the KLF family in CRC. The results were then further validated using an in-house cohort (n=194). Univariate and multivariate Cox proportional hazards models were used to assess the risk factors for survival. In the TCGA cohort, KLF3 (hazard ratio [HR], 0.501; 95% confidence interval [CI], 0.272-0.920; P=0.025), KLF14 (HR, 1.454; 95% CI, 1.059-1.995; P=0.020), and KLF17 (HR, 1.241; 95% CI, 1.030-1.494, P=0.023) were identified as potential biomarkers in the univariate analysis, but after Cox proportional hazards analysis, only KLF3 (HR, 0.473; 95% CI, 0.230-0.831; P=0.012) was shown to be independently predictive of overall survival in patients with CRC. This finding was validated in our in-house cohort, which demonstrated that KLF3 expression was an independent predictor of both overall survival (HR, 0.628; 95% CI, 0.342-0.922; P=0.035) and disease-free survival (HR, 0.421; 95% CI, 0.317-0.697, P=0.016). KLF3 expression was inversely correlated with the N stage (P=0.015) and lymphovascular invasion (P=0.020). Collectively, loss of KLF3 was correlated with aggressive phenotypes and poor survival outcomes. KLF3 might be a potential new predictor and therapeutic target for CRC. Further study is needed for a more detailed understanding of the role of KLF3 in CRC.

Response to Pegylated Interferon Plus Ribavirin in Patients with Hepatitis C Virus Genotype 6a Infection from Guangdong and Guangxi Province of China.

Aim. Our aim is to survey the treatment effect of PEG-IFN plus ribavirin in patients infected with HCV genotype 6a in Guangdong and Guangxi province of China and investigate best course of antiviral treatment for patients with HCV-6a infection. Methods. 515 eligible patients received subcutaneous 180 µg PEG-IFNα-2a or 1.5 µg/kg PEG-IFNα-2b once weekly plus oral ribavirin. Primary outcome was SVR by intention-to-treat analysis. Secondary outcome was RVR, cEVR, ETR, and relapse rate. Results. SVR in patients with HCV-6a infection treated for 48 weeks was comparable to that in patients with HCV-2/3 infection (80.9% versus 82.5%, p = 0.812) and higher than that in patients with HCV-1b infection (80.9% versus 67.2%, p = 0.014). ETR (98.9% versus 90.6%, p = 0.016), virological response at month 3 of end-of- treatment (88.8% versus 76.6%, p = 0.044), SVR (80.9% versus 65.6%, p = 0.032), and virological response at month 12 of end-of-treatment (76.4% versus 60.9%, p = 0.04) in patients with HCV-6a infection treated for 48 weeks were higher than those in patients with HCV-6a infection treated for 24 weeks. Conclusion. SVR in patients with HCV-6a treated for 48 weeks was comparable to that in patients with HCV-2/3 infection and higher than that in patients with HCV-1b infection; patients with HCV-6a infection treated for 48 weeks had a superior treatment response than patients treated for 24 weeks.