[The effect of wza gene deletion in Klebsiella pneumoniae on capsule formation and bacteriophage sensitivity].

Objective: To investigate the effects of wza gene deletion in Klebsiella pneumoniae on capsule formation ability and bacteriophage sensitivity. Methods: The wza deletion mutant strain was constructed through a temperature-sensitive plasmid-mediated homologous recombination. The growth curves of W14 and Δwza were detected by measuring the optical density OD600. In order to analyze the effect of gene wza on bacterial capsule formation, wild-type strain W14 and Δwza mutant strain were detected by transmission electron microscope, and their capsule contents were measured by quantifying the uronic acid contents. The plaque assay was used to detect bacterial sensitivity to bacteriophage in wild-type strain W14 and Δwza mutant strain. The t test was used to compare whether there were differences in the contents of uronic acid in the capsules of wild-type strain W14 and Δwza mutant strain. Results: The PCR results revealed that the Δwza mutant strain was successfully constructed. Compared with wild-type strain W14, the growth curves of Δwza on the solid plates demonstrated a slightly slower growth. However, no difference in growth was observed among wild-type strain W14 and Δwza mutant strains in LB broth. The transmission electron microscope results showed that wza gene deletion resulted in the loss of capsule in bacteria. The uronic acid content assay suggested that the capsule content was significantly decreased in Δwza mutant strain (45.963±2.795) µg/ml compared with wild-type strain W14 (138.800±5.201) µg/ml. There was a statistical difference between the two groups (t=27.233, P<0.001). The plaque assay indicated that bacteria lost its sensitivity to bacteriophage when gene wza was deleted. Conclusion: Deletion of the wza gene impairs bacterial capsule formation ability and can affect bacterial sensitivity to bacteriophage phiW14.

Robotic versus laparoscopic left colectomy with complete mesocolic excision for left-sided colon cancer: a multicentre study with propensity score matching analysis.

BACKGROUND: Robotic surgery for right-sided colon and rectal cancer has rapidly increased; however, there is limited evidence in the literature of advantages of robotic left colectomy (RLC) for left-sided colon cancer. The purpose of this study was to compare the outcomes of RLC versus laparoscopic left colectomy (LLC) with complete mesocolic excision (CME) for left-sided colon cancer. METHODS: Patients who had RLC or LLC with CME for left-sided colon cancer at 5 hospitals in China between January 2014 and April 2022 were included. A one-to-one propensity score matched analysis was performed to decrease confounding. The primary outcome was postoperative complications occurring within 30 days of surgery. Secondary outcomes were disease-free survival, overall survival and the number of harvested lymph nodes. RESULTS: A total of 292 patients (187 males; median age 61.0 [20.0-85.0] years) were eligible for this study, and propensity score matching yielded 102 patients in each group. The clinical-pathological characteristics were well-matched between groups. The two groups did not differ in estimated blood loss, conversion to open rate, time to first flatus, reoperation rate, or postoperative length of hospital stay (p > 0.05). RLC was associated with a longer operation time (192.9 ± 53.2 vs. 168.9 ± 52.8 minutes, p=0.001). The incidence of postoperative complications did not differ between the RLC and LLC groups (18.6% vs. 17.6%, p = 0.856). The total number of lymph nodes harvested in the RLC group was higher than that in the LLC group (15.7 ± 8.3 vs. 12.1 ± 5.9, p< 0.001). There were no significant differences in 3-year and 5-year overall survival or 3-year and 5-year disease-free survival. CONCLUSIONS: Compared to laparoscopic surgery, RLC with CME for left-sided colon cancer was found to be associated with higher numbers of lymph nodes harvested and similar postoperative complications and long-term survival outcomes.

A Non-Invasive Method for Monitoring Osteogenesis and Osseointegration Using Near-Infrared Fluorescent Imaging: A Model of Maxilla Implantation in Rats.

Currently, computed tomography and conventional X-ray radiography usually generate a micro-artifact around metal implants. This metal artifact frequently causes false positive or negative diagnoses of bone maturation or pathological peri-implantitis around implants. In an attempt to repair the artifacts, a highly specific nanoprobe, an osteogenic biomarker, and nano-Au-Pamidronate were designed to monitor the osteogenesis. In total, 12 Sprague Dawley rats were included in the study and could be chategorized in 3 groups: 4 rats in the X-ray and CT group, 4 rats in the NIRF group, and 4 rats in the sham group. A titanium alloy screw was implanted in the anterior hard palate. The X-ray, CT, and NIRF images were taken 28 days after implantation. The X-ray showed that the tissue surrounded the implant tightly; however, a gap of metal artifacts was noted around the interface between dental implants and palatal bone. Compared to the CT image, a fluorescence image was noted around the implant site in the NIRF group. Furthermore, the histological implant-bone tissue also exhibited a significant NIRF signal. In conclusion, this novel NIRF molecular imaging system precisely identifies the image loss caused by metal artifacts and can be applied to monitoring bone maturation around orthopedic implants. In addition, by observing the new bone formation, a new principle and timetable for an implant osseointegrated with bone can be established and a new type of implant fixture or surface treatment can be evaluated using this system.

Addition of dexamethasone to manage acute phase responses following initial zoledronic acid infusion.

Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is the most common adverse reaction to initial zoledronic acid infusion. Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR. INTRODUCTION: Acute phase response (APR), including myalgia, influenza-like symptoms, headache, arthralgia, and pyrexia, is due to immunomodulatory actions and is the most common adverse reaction to zoledronic acid (ZOL). The aims of our study were to compare the differences between acetaminophen and dexamethasone plus acetaminophen on the incidence and severity of APRs and to clarify the clinical factors related to APR with initial ZOL infusion. METHODS: Patients with osteoporosis receiving their first ZOL infusion (N = 96) were assigned into two groups and given either acetaminophen (58 patients, control group) or acetaminophen plus dexamethasone (38 patients, study group). APRs were assessed through telephone interviews 2 weeks later post-infusion. Clinical, demographic, and serologic data were recorded. RESULTS: There was a significant increase in the incidence and severity of any APR in the control group than the study group (67% vs. 34%, p = 0.003; 0.69 ± 0.50 vs. 0.34 ± 0.48, p = 0.001). Among the APRs, only myalgia incidence and score were significantly higher in the control group than in the study group. Multivariate analysis demonstrated that previous use of osteoporosis medication and participation in the study group was negatively related to the occurrence of any APR or myalgia. Advanced age was shown to significantly increase myalgia. Study group participants had significantly reduced severity of myalgia. The adherence for redosing ZOL was significantly higher in the study group. CONCLUSION: Dexamethasone plus acetaminophen is effective in significantly reducing the incidence and severity of APR, especially myalgia, and increasing adherence following initial ZOL infusion.

Effects of the circadian rhythm on milk composition in dairy cows: Does day milk differ from night milk?

Metabolism in most organisms can show variations between the day and night. These variations may also affect the composition of products derived from livestock. The aim of the present study was to investigate the difference in composition between the day milk and night milk of dairy cows. Ten multiparous Holstein cows (milk yield = 25.2 ± 5.00 kg/d) were randomly selected during mid lactation. Milk samples were collected at 0500 h ("night milk") and 1500 h ("day milk") and analyzed to determine their composition. Mid-infrared spectroscopy was used to analyze macronutrient content of milk. Metabolomics and lipidomics were used to detect and analyze small molecules and fatty acids, respectively. An automatic biochemical analyzer and ELISA kits were used to determine biochemical indicators, as well as antioxidant and immune parameters in the milk. Though milk fat, protein, lactose, and total milk solids were not different between day milk and night milk, small molecules, metabolites and lipids, and hormones and cytokines differed between day milk and night milk. Regarding biochemical and immune-related indicators, the concentrations of malondialdehyde, HSP70, and HSP90 in night milk were lower than that in day milk. However, interferon-γ levels were higher in night milk. Additionally, night milk was naturally rich in melatonin. Lipidomics analyses showed that the levels of some lipids in night milk were higher than those in day milk. Metabolomics analyses identified 36 different metabolites between day milk and night milk. Higher concentrations of N-acetyl-d-glucosamine, cis-aconitate, and d-sorbitol were observed in day milk. However, the other 33 metabolites analyzed, including carbohydrates, lipids, AA, and aromatic compounds, showed lower concentrations in day milk than in night milk. The present findings show that the composition of night milk differs considerably from that of day milk. Notable changes in the circadian rhythm also altered milk composition. These results provide evidence to support the strategic use and classification of day milk and night milk.

[Diagnostic accuracy of liver and spleen stiffness by two dimensional shear wave elastography for portal hypertension in hepatitis B-related cirrhosis].

Objective: To assess the diagnostic accuracy of liver and spleen stiffness measured by two dimensional shear wave elastography (2D-SWE) in hepatitis B-related cirrhosis. Methods: The clinical data of fifty-eight hepatitis B-related cirrhosis patients were collected in Zhongshan Hospital, Fudan University from September 2017 to April 2018. Pearson's correlation analyses were used to assess the relationship between liver/spleen stiffness (L-SWE and S-SWE) and hepatic venous pressure gradient (HVPG), as well as the comparison with serological model. The SWE diagnostic performances of Liver (L-SWE), Spleen (S-SWE) were also evaluated. Results: Of all 58 patients, 47 were found HVPG ≥10 mmHg, diagnosed as clinically significant portal hypertension (CSPH) and severe portal hypertension (SPH), which patients are at increased risk of developing complications. Thirty-four patients were found HVPG≥12 mmHg, diagnosed as SPH, which patients were at increased risk of variceal bleeding. Moderate positive correlation was found between L-SWE and HVPG (r=0.42, P<0.01), and S-SWE were significantly correlated with HVPG (r=0.68, P<0.01), while serological models and HVPG were slightly correlated (r=0.36 and 0.28, all P<0.01). The area under the receiver operating characteristic curves of L-SWE, S-SWE and the combination for CSPH were 0.78, 0.88 and 0.89. When L-SWE was>12.86 kPa or S-SWE was>35.73 kPa, patients were at increased risk of developing complications. The area under the receiver operating characteristic curves for SPH were 0.68, 0.81 and 0.77 and the S-SWE had the highest specificity, so when S-SWE was>41.5 kPa, patients were at increased risk of variceal bleeding. Conclusion: L-SWE and S-SWE are reliable and promising non-invasive parameters to assess CSPH and SPH.

[Predictive value of two-dimentional shear wave elastography in posthepatoectomy liver failure].

Objective: To investigate the value of two-dimensional shear wave elastography (2D SWE) combined with clinical biochemical data in predicting posthepatoectomy liver failure (PHLF) in patients with hepatocellular carcinoma (HCC). Methods: A total of 274 HCC patients who underwent hepatectomy in Zhongshan Hospital Fudan University from January 2015 to January 2016 were retrospectively collected, including 235 males and 39 females, age 19-80 (56±11) years. All patients were confirmed to be HCC by postoperative pathology. The preoperative 2D SWE examination, laboratory examination results and intraoperative indicators were analyzed. According to the occurrence of PHLF after surgery, single factor analysis and multiple logistic regression analysis were performed on the above indicators to obtain a binary logistic regression model, and evaluate the diagnostic effect of the model on PHLF. In addition, 103 HCC patients from October 2019 to January 2020 were retrospectively collected as an external validation set, including 89 males and 14 females, age 23-80 (55±11) years old. Results: The liver stiffness measurement (LSM) obtained from 2D SWE, INR and Laminin (LN) were independent predictors of PHLF. The formula of prediction model PM=-15.451+0.095×LSM+11.7×INR+0.012×LN was obtained by combining above three factors. The area under the curve (AUC) of PHLF was 0.82, which was higher than that of end-stage liver disease model (MELD) score and Child-Pugh grading diagnosis of PHLF. The AUC of PHLF predicted by PM in the external validation group was 0.81. Conclusion: 2D SWE is helpful for clinicians to evaluate liver reserve function preoperatively and to predict the occurrence of PHLF in patients with HCC.

Glycidamide Promotes the Growth and Migratory Ability of Prostate Cancer Cells by Changing the Protein Expression of Cell Cycle Regulators and Epithelial-to-Mesenchymal Transition (EMT)-Associated Proteins with Prognostic Relevance.

Acrylamide (AA) and glycidamide (GA) can be produced in carbohydrate-rich food when heated at a high temperature, which can induce a malignant transformation. It has been demonstrated that GA is more mutagenic than AA. It has been shown that the proliferation rate of some cancer cells are increased by treatment with GA; however, the exact genes that are induced by GA in most cancer cells are not clear. In the present study, we demonstrated that GA promotes the growth of prostate cancer cells through induced protein expression of the cell cycle regulator. In addition, we also found that GA promoted the migratory ability of prostate cancer cells through induced epithelial-to-mesenchymal transition (EMT)-associated protein expression. In order to understand the potential prognostic relevance of GA-mediated regulators of the cell cycle and EMT, we present a three-gene signature to evaluate the prognosis of prostate cancer patients. Further investigations suggested that the three-gene signature (CDK4, TWIST1 and SNAI2) predicted the chances of survival better than any of the three genes alone for the first time. In conclusion, we suggested that the three-gene signature model can act as marker of GA exposure. Hence, this multi-gene panel may serve as a promising outcome predictor and potential therapeutic target in prostate cancer patients.

[Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B: an exploratory research].

Objective: To establish automatic liver fibrosis classification models by using traditional machine learning and deep learning methods and preliminaryly evaluate the efficiency. Methods: Gray scale ultrasound images and corresponding elastic images of 354 patients, 247 males and 107 females, mean age (54±12) years undergoing partial hepatectomy in Zhongshan Hospital of Fudan University from November 2014 to January 2016 were enrolled in this study. By using traditional machine learning and deep learning methods, an automatic classification model of liver fibrosis stages (S0 to S4) were established through feature extraction and classification of ultrasound image data sets and the accuracy in different classification categories of each model were calculated, by using liver biopsy as the reference standard. Results: Pathological examination showed 73 cases in pathological stage S0, 40 cases in S1, 49 cases in S2, 41 cases in S3, and 151 cases in S4. The traditional machine classification model based on support vector machine (SVM) classifier and sparse representation classifier and the deep learning classification model based on LeNet-5 neural network, their accuracy rates in the two categories (S0/S1/S2 and S3/S4) were 89.8%, 91.8% and 90.7% respectively; the accuracy rates in the three categories (S0/S1 and S2/S3 and S4) were 75.3%, 79.4% and 82.8% respectively; the accuracy in the three categories (S0 and S1/S2/S3 and S4) were 79.3%, 82.7% and 87.2% respectively. Conclusions: Computer-aided assessment of liver fibrosis progression in patients with chronic hepatitis B has a high accuracy, and can achieve a more detailed classification. This method is expected to be applied in the non-invasive evaluation of liver fibrosis in patients with hepatitis B in clinical work in the future.

Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.

Trastuzumab combined with doublet or single-agent chemotherapy as first-line therapy for HER2-positive metastatic breast cancer.

PURPOSE: To investigate the efficacy and safety of doublet versus single-agent chemotherapy (CT) plus trastuzumab (H) as first-line therapy for human epidermal growth factor 2 receptor (HER2)-positive metastatic breast cancer (MBC). METHODS: We searched for randomized clinical trials (RCTs) that evaluated the treatment effects of single-agent or doublet CT+H as first-line therapies for HER2-positive MBC. The main outcomes measured for this study included the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). A meta-analysis and trial sequential analysis (TSA) were performed, and the study quality was evaluated using the GRADE framework. The PROSPERO registry number of our analysis is CRD42016043766. RESULTS: The results from four RCTs including 1044 participants were pooled. Moderate-quality evidence indicated that compared with single-agent CT+H, doublet CT+H correlated better with prolonged PFS (hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.63-0.75, P < 0.0001) and OS (HR = 0.90, 95% CI 0.88-0.92, P < 0.0001). However, moderate-quality evidence revealed no significant difference between the two regimens regarding the ORR (relative risk [RR] = 1.07, 95% CI 0.98-1.17, P = 0.157), which was confirmed by TSA, indicating that the cumulative Z-curve entered the futility area. Moderate-quality evidence indicated that treatment-related grade 3 or 4 toxicities of thrombocytopenia (RR = 4.08, P = 0.000), nausea/vomiting (RR = 4.26, P = 0.002), diarrhea (RR = 2.81, P = 0.002), and stomatitis (RR = 5.02, P = 0.003) were observed more frequently with doublet CT+H than with single-agent CT+H. CONCLUSIONS: Compared with single-agent CT, the combination of doublet CT with trastuzumab as first-line therapy for HER2-positive MBC is associated with longer PFS and OS, but more treatment-related grade 3 or 4 toxicities. Therefore, doublet CT appears to be an appropriate regimen for HER2-positive MBC with a good performance status.

Patient-specific models of microglia-mediated engulfment of synapses and neural progenitors.

Engulfment of synapses and neural progenitor cells (NPCs) by microglia is critical for the development and maintenance of proper brain circuitry, and has been implicated in neurodevelopmental as well as neurodegenerative disease etiology. We have developed and validated models of these mechanisms by reprogramming microglia-like cells from peripheral blood mononuclear cells, and combining them with NPCs and neurons derived from induced pluripotent stem cells to create patient-specific cellular models of complement-dependent synaptic pruning and elimination of NPCs. The resulting microglia-like cells express appropriate markers and function as primary human microglia, while patient-matched macrophages differ markedly. As a demonstration of disease-relevant application, we studied the role of C4, recently implicated in schizophrenia, in engulfment of synaptic structures by human microglia. The ability to create complete patient-specific cellular models of critical microglial functions utilizing samples taken during a single clinical visit will extend the ability to model central nervous system disease while facilitating high-throughput screening.

Sol-Gel Derived Antibacterial Ag-Containing ZnO Films on Biomedical Titanium.

ZnO and Ag-containing ZnO (ZnO/Ag) films with the Ag/Zn molar ratio of 3.3 and 9.1%, respectively were sol-gel coated on biomedical titanium for antibacterial and bioactive surface modification. X-ray diffraction analysis indicates that ZnO peaks increase with the calcination temperature of the samples. Scanning electron microscopy and energy dispersive of X-ray analyses reveal Ag-rich white particles (300~750 nm) on ZnO/Ag samples that were calcined at 400 °C. X-ray photoelectron spectroscopy analysis of ZnO/Ag samples shows that Zn and O exist as ZnO and Ag presents in metallic state. The coating samples exhibit similar UV light-induced hydrophilic conversion behavior. Potentiodynamic polarization test in a Ca-free Hank's balanced solution demonstrates better corrosion resistance of the coating samples compared with the polished sample. In the in vitro bioactivity test using the simulated body fluid, a layer of apatite is gradually deposited on the surface of sample ZnO/9Ag after 12 days of soaking. The MTT assay test shows that ZnO and ZnO/Ag films have weak compatibility with the L929 cells. The antibacterial test against E. Coli by the disk diffusion assay reveals that antibacterial activity of the coating samples increases with silver content of the films.

Effectiveness of telephone-based interventions on health-related quality of life and prognostic outcomes in breast cancer patients and survivors-A meta-analysis.

The aim of this meta-analysis was to evaluate the effect of telephone-based interventions on prognostic outcomes and health-related quality of life (HRQoL) in breast cancer patients and survivors. A systematic search of the Cochrane Library, Web of science, Medline, EMBASE, CNKI and CBM database was carried out. Randomised, controlled trials (RCTs) examining the effects of telephone-based intervention versus a control group receiving no telephone intervention, on prognostic outcomes and HRQoL with breast cancer were included. A meta-analysis was conducted to quantify the effects of telephone-based interventions on anxiety, depression, fatigue, self-efficiency, physiological function, social-domestic function and quality of life. In total, 14 studies involving 2002 participants were included. Due to the effect of telephone-based interventions, statistically significant results were found on anxiety (standard mean difference [SMD] = -0.16, 95% confidence intervals [CI] [0.01, 0.30], p = .04), self-efficiency (SMD = 0.22, 95% CI [-0.34, -0.10], p = .0004), social-domestic function (SMD = 0.19, 95% CI [-0.35, -0.03], p = .02) and quality of life (SMD = 0.54, 95% CI [-1.00, -0.08], p = .02). Although the effects on depression, fatigue and physiological function were in the expected direction, these effects were not statistically significant (p > .05) based on the insufficient evidence.

[Airway foreign body caused by aspiration of artificial nasal sponge: a case report].

57-year-old male was admitted to hospital for severe headache and seizure attacks on November 6th, 2016. After radiology and spinal fluid examination, he was diagnosed with viral encephalitis and treated with antiviral medicine, antibiotics and mannitol, but he was in sustained unconsciousness and weak in expectorating. The patient was given oxygen through artificial nasal after bedside tracheotomy. At 1:00 am on January 12th, 2016, there was a sudden drop in blood pressure, heart rate and oxygen saturation with left lung breath sounds slightly lower than the other side. The patient was connected to a ventilator with tidal volume of 300-500 mL and airway pressure of 16-24 cmH2O (1 cmH2O=0.098 kPa). In the meanwhile, the left side sponge of artificial nasal was found missing. Bedside chest X-ray showed no significant atelectasis. At that time the evidence of airway foreign body aspiration was not sufficient, so no urgent bronchoscopy was performed. At 9:00 am on January 14th, 2016, there was another sudden decline in oxygen saturation with diminished left lung breath sounds and decreased left thoracic activity. Since left atelectasis could not be ruled out, bedside bronchoscopy was performed. In the operation, two sponge-like objects were found at the left main bronchus and the opening of left upper lobe bronchial. Foreign body forceps were used to remove them. The foreign bodies were proved to be the left sponge of artificial nasal afterwards. Symptoms and signs caused by aspiration of foreign body in adults were widely various and depending on the nature of the foreign body, site, time and whether there was infection or not. Foreign body aspiration caused by artificial nasal sponge was rare in clinical practice. This case was a living reminder to perform bronchoscopy when foreign body aspiration was suspected. For the unconscious and elderly patient, whose history of foreign body aspiration usually could not be clearly provided, when atelectasis was suspected, bronchoscopy should be performed progressively, and more effective measures should be taken to prevent sponge of artificial nasal displacement.

DEPDC5 mutations in familial and sporadic focal epilepsy.

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.

Secular trends in incidence and recurrence rates of hip fracture: a nationwide population-based study.

We assessed the incidence of hip fracture and second hip fractures in Taiwan from 2001 to 2012. Age-standardized incidence rates decreased after 2005. However, mortality rate after first hip fracture was substantial compared to second hip fracture rate in a competing risk model. INTRODUCTION: The aim of the study is to assess the incidence rates (IRs) of hip fractures, including changes in trends and medical costs, and second hip fractures in the Taiwanese population. METHODS: The number of hip fractures and the associated medical costs were obtained from the annual report of the Ministry of Health and Welfare, Taiwan, for individuals ≥50 years of age. The data of population at risk were retrieved from annual population reports from the Ministry of the Interior, Taiwan. The incidence of second hip fractures was evaluated from the National Health Insurance Research Database of Taiwan for insured individuals aged ≥50 years from 2001 to 2011 with follow-up until 2013 using a competing risk model. RESULTS: The IR for the entire population increased from 332.7 to 336.5 per 100,000 person-years during 2001-2005 and decreased thereafter. This secular change was driven by a decrease in hip fractures for both men and women. The 10-year cumulative incidence rate of second hip fracture was 11.2% (95% CI 11.0-11.5%) in women and 7.9% (95% CI 7.6-8.1%) in men. Adjusted by consumer price index (CPI), the costs of hospitalization due to hip fracture increased from NTD 1.17 billion in 2001 to NTD 1.43 billion in 2012. However, the CPI-adjusted costs of each admission decreased from NTD 74944 in 2001 to NTD 65791 in 2012. CONCLUSIONS: Since 2006, the IR of hip fractures has been declining in Taiwan. The 10-year cumulative IR of mortality is substantial for individuals who with first hip fracture.

Differential expression of hENT1 and hENT2 in colon cancer cell lines.

Human equilibrative nucleoside transporters (hENT) 1 and 2, encoded by SLC29A1 and SLC29A2, permit the bidirectional passage of nucleoside analogues into cells and may correlate with clinical responses to chemotherapy in patients with colorectal cancer (CRC). The purpose of this study was to evaluate the expression profiles of SLC29A1 and SLC29A2 in human cancer cell lines. Using quantitative real-time polymerase chain reaction, we comprehensively profiled the transcription levels of SLC29A1 and SLC29A2 in 16 colon cancer cell lines. We validated the ubiquitous and heterogeneous distribution of SLC29A1 and SLC29A2 in human colon cancer cell lines and demonstrated that SLC29A1 was highly expressed in 25% of metastatic cell lines (Colo201 and Colo205) and 62.5% of primary cell lines (Caco2, Colo320, HCT116, RKO, and SW48). For the first time, we showed that both SLC29A1 and SLC29A2 were expressed at lower levels in colon cancer cell lines originating from metastatic sites than from primary sites. These findings indicate that most patients with metastatic CRC (mCRC) may have low hENT1 expression, and treatment with nucleoside analogues may be inefficient. However, some patients still show high hENT1 expression and have a high probability of benefiting from these drugs. Therefore, evaluating transporter expression profiles and different drug responses between primary and metastatic tumors in patients with mCRC is important. Further assessment of the association between hENTs and drug-based treatment of mCRC is required to elucidate the mechanisms of chemotherapy resistance.

Identification and functional characterization of four transient receptor potential ankyrin 1 variants in Apolygus lucorum (Meyer-Dür).

As signal integrators that respond to various physical and chemical stimuli, transient receptor potential (TRP) channels fulfil critical functional roles in the sensory systems of both vertebrate and invertebrate organisms. Here, four variants of TRP ankyrin 1 (TRPA1) were identified and cloned from the green plant bug, Apolygus lucorum. Spatiotemporal expression profiling across development and in different adult tissues revealed that the highest relative-transcript levels occurred in first-instar nymphs and antennae, respectively. In Xenopus laevis-based functional assays, Apo. lucorum TRPA1-A (AlucTRPA1-A), AlucTRPA1-B and AlucTRPA1-C were activated by increasing the temperature from 20 to 40 °C with no significant desensitization observed after repeated temperature stimuli. The activation temperature of AlucTRPA1-A and AlucTRPA1-B was < 25 °C, whereas the activation temperature of AlucTRPA1-C was between 25 and 30 °C. Amongst the variants, only AlucTRPA1-A and AlucTRPA1-C were directly activated by high concentrations of allyl isothiocyanate, cinnamaldehyde and citronellal. Taken together, these results suggest that AlucTRPA1 variants may function in vivo as both thermal and chemical sensors, with the four variants potentially mediating different physiological functions. This study not only enriches our understanding of TRPA1 function in Hemiptera (Miridae), but also offers a foundation for developing new pest control strategies.

[Predictor measures on CT for hematoma expansion following acute intracerebral hemorrhage].

OBJECTIVE: To evaluate the worth of solid predictors in acute intracerebral hematoma(ICH) expansions in computer tomography images. METHODS: A total of 105 patients with acute ICH in The Second Affiliated Hospital of Soochow University during January 2012 to February 2015 were enrolled. CT plain scan, CTA within 6 hours since the symptoms and CT plain scan recheck within 24 hours were executed. Hematoma location, initial volume of hematoma, shape of hematoma, "spot sign" , UHG speed were analyzed with single factor and binary Logistic regression between the patients with and without hematoma expansion. RESULTS: There were 30 cases with hematoma expansion and 75 cases with no hematoma expansion in 105 patients. In single factor comparisons, hematoma location(χ(2) =13.125, P<0.05), hematoma shape(χ(2) =23.987, P<0.05), spot sign(χ(2) =25.846, P<0.05), UHG speed(χ(2) =20.328, P<0.05) and the initial hematoma volume(t=-3.183, P<0.05) between the hematoma expansions and the non-hematoma expansions made significant differences. In binary Logistic regression, hematoma shape(irregular (P=0.033) and cleavage(P=0.009)), spot sign(P=0.000) and UHG speed(P=0.040) had significant differences between the two groups. ROC curve areas of hematoma shape, spot sign and UHG speed were 0.776(95%CI 0.682-0.870), 0.740(95%CI 0.625-0.855) and 0.720(95% CI 0.604-0.836). The high specificities of hematoma shape(84%), spot sign (88%)and UHG speed(84%)revealed their great reliabilities with equal sensitivity (60%). CONCLUSION: Hematoma shape, spot sign and UHG speed are solid predictors of hematoma expansion among which spot sign has promising specificity, hematoma shape and UHG speed are more convenient to be observed.