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Objectives To evaluates the role of diet in determining knee osteoarthritis risk. Methods Literature search was conducted in Ovid, PubMed, Science Direct, and Springer. To estimate knee osteoarthritis risk with high use of vegetarian, prudent, and omnivorous diets, dairy products, vitamin C/E, and carotenoids, the odds ratios (ORs) or relative risks (RRs) reported by included studies were pooled. Results Fifteen studies (97,157 individuals) were included. High use of vegetarian diet {OR 0.71 [95% confidence interval (CI): 0.45, 0.97]}, prudent diet [OR 0.87 (95% CI: 0.76, 0.98)/RR 0.89 (95% CI: 0.82, 0.97)], and dairy [OR 0.66 (95% CI: –0.08, 1.39)/RR 0.58 (95% CI: 0.41, 0.75)] were associated with lower risk of knee osteoarthritis but risk was relatively higher with high use of omnivorous diet [OR 1.13 (95% CI: 0.95, 1.30)/RR 1.06 (95% CI: 0.84, 1.29) and 1.05 (0.78, 1.33)]. High intake of vitamin C [OR 0.92 (0.29, 1.56)] or E [OR 0.93 (0.64, 1.21)] did not reduce knee osteoarthritis risk, but high use of carotenoids was associated with the lower risk [OR 0.66 (0.37, 0.96)]. Conclusions Knee osteoarthritis risk is low with high use of vegetarian diet, prudent diet, and dairy, but cannt be reduced by high intakes of vitamin C/E.

BACKGROUND At present, the value of lipid indicators in evaluating the prognosis of colorectal cancer is still relatively limited. AIM To evaluate the value of a novel parameter for colorectal cancer (CRC) prognosis scoring based on preoperative serum lipid levels. METHODS Four key serum lipid factors, namely, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (ApoA1), and apolipoprotein B (ApoB), were detected. Two representative ratios, HDL-C-LDL-C ratio (HLR) and ApoA1-ApoB ratio (ABR) were calculated. The relationship of these parameters with the prognosis of CRC patients including progression-free survival (PFS) and overall survival (OS) was analyzed by Kaplan-Meier plot and Cox proportional hazards regression. A novel lipoprotein cholesterol-apolipoprotein (LA) score based on HLR and ABR was established and its value in prognosis evaluation for CRC patients was explored. RESULTS Multivariate Cox proportional hazards regression analysis of PFS and OS showed that HDL-C, ApoA1, HLR, and ABR were positively associated with the prognosis of CRC patients. LA score was independently associated with a good prognosis in resectable CRC patients. Data processing of a dummy variable showed that the prognosis of patients with higher LA scores is better than that with lower LA scores. CONCLUSION The newly established LA score might serve as a better predictor of the prognosis of resectable CRC patients.

Oral squamous cell carcinoma is one of the most common high malignant tumors. This experiment aimed to investigate whether ethyl acetate extract of peony (Paeonia suffruticosa) seed coat could affect the proliferation and apoptosis of oral squamous carcinoma cells by regulating the miR-424-3p/STAT3/Survivin pathway. For this purpose, oral squamous cell carcinoma cell CAL27 was cultured in vitro, and cells were treated with ethyl acetate extract of peony seed coat at different concentrations. MTT was used to detect cell proliferation. Flow cytometry was used to detect apoptosis. qRT-PCR was used to detect the expression level of miR-424-3p. The miR-424-3p mimics and anti-miR-424-3p were transfected into CAL27 cells respectively, and the cell proliferation and apoptosis were detected by the above method. Western blot method was used to detect the expression of PCNA, Bcl-2, Bax, p-STAT3 and Survivin protein. Results showed that ethyl acetate extract of peony seed coat could reduce cell proliferation rate and the protein levels of PCNA, Bcl-2, p-STAT3, Survivin and the expression level of miR-424-3p (P

Background Computed tomography perfusion (CTP) can provide information on blood perfusion as a reliable marker of tumor response to therapy. Purpose To assess the role of volume CTP (vCTP) parameters in predicting treatment response to concurrent chemoradiotherapy (CCRT) for cervical cancer. Material and Methods Thirty-three patients with cervical cancer underwent vCTP. Three CTP parameters of cervical cancer—including arterial flow (AF), blood volume (BV), and permeability surface (PS)—were measured in two different ways: the region of interest incorporating the “local hot” with the highest enhancement and “cold spot” with the lowest enhancement; and “whole-tumor” measurements. The patients were divided into non-residual and residual tumor groups according to the short-term response to treatment. The clinical and perfusion parameters were compared between the two groups. Results There was no significant difference in age, body mass index, FIGO stage, pathological grade, or pretreatment tumor size between the two groups ( P > 0.05). The non-residual tumor group had higher pretreatment AF in high-perfusion and low-perfusion subregions than the residual tumor group ( P 0.05). There were no differences in BV and PS between the two groups ( P > 0.05). The diagnostic potency of AF in the low-perfusion subregion was higher than that in the high-perfusion subregion. Conclusion vCTP parameters are valuable for the prediction of short-term effects. The AF in the low-perfusion subregion was a more effective index for predicting treatment response to CCRT of cervical cancer.

Objectives Eurycoma longifolia Jack (Simaroubaceae) is commonly distributed in the Southeast Asia and Indo China, which has been shown to possess antianxiety, antibacterial, anticancer, antifungal, anti-inflammatory, antimalarial and antioxidant biological activities. 14,15β-dihydroxyklaineanone is a diterpene isolated from E. longifolia Jack, which is cytotoxic against human lung cancer and human breast cancer cell lines. However, the effects and underlying mechanisms of 14,15β-dihydroxyklaineanone on hepatocellular carcinoma remain unknown. Methods Cell viability assay and colony formation assay were used to measure HepG2 cell proliferation. Flow cytometry was used to analyse cell cycle and apoptosis. Wound-healing assay and transwell assay were used to observe cells migration. RNA sequencing and the enrichment of differentially expressed genes (DEGs) in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to find and determine underlying pathways. Key findings We found that 14,15β-dihydroxyklaineanone inhibited the growth and migration of HepG2 cells but did not induce cell apoptosis. 14,15β-dihydroxyklaineanone induced S cell cycle arrest by downregulating the expression levels of cyclin A, p-CDK2, cyclin B1, p21, E2F-1 and PCNA. In addition, RNA sequencing showed that 14,15β-dihydroxyklaineanone regulated MAPK pathway by increasing the expression levels of phosphor-p38. Downregulating of p38 via both p38 inhibitor (SB203580) and p38-siRNA could antagonize the inhibition of cell proliferation and migration and reverse the changes in p-p38, E-cadherin, N-cadherin and PCNA expression induced by 14,15β-dihydroxyklaineanone treatment. Conclusions 14,15β-dihydroxyklaineanone inhibited cell proliferation and migration through regulating p38 MAPK pathway in HCC cells.

In this study, several representative deep eutectic solvents (DESs) were designed to evaluate the solubility for alkali lignin (AL). It was found that DESs with lactic acid (LA) as hydrogen bond donors (HBDs) had good solubility for AL, in which lactic acid(LA) : choline chloride(ChCl) 10 : 1 showed excellent solubility with more than 17 wt% under a relatively mild condition of 60 °C. The results of gel permeation chromatography (GPC), FTIR and 1H and HSQC NMR spectroscopies revealed an important possible dissolution mechanism of AL in LA-ChCl, that is, AL could be depolymerized under the action of LA when dissolved in LA-ChCl. Then, a new connection would form between the phenolic groups on the lignin fragments and ChCl, which is similar to that between ChCl and LA in DES, leading to an increase in the molecule weight of lignin. The new connections could be easily broken under the action of heat (150 °C) or microwave to the redispersion of lignin fragments. The results would provide a theoretic base for the high-value application of lignin in bioresources.

Toothbrushing epilepsy is a rare form of reflex epilepsy (RE) with sporadic incidence. To characterize the genetic profile of reflex epilepsy patients with tooth brushing-induced seizures in a Chinese family. Solo clinical whole-exome sequencing (WES) of the proband, a 37-year-old Chinese man, was performed to characterize the genetic etiology of toothbrushing epilepsy. Mutations in the maternal X-linked synapsin 1 (SYN1) identified in the proband and his family members were confirmed by Sanger sequencing. The pathogenicity of these mutations was determined using in silico analysis. The proband had four episodes of toothbrushing-induced seizures. The semiology included nausea, twitching of the right side of the mouth and face, followed by a generalized tonic-clonic seizure (GTCS). The proband's elder maternal uncle had three toothbrushing-induced epileptic seizures at the age of 26. The proband's younger maternal uncle had no history of epileptic seizures but had a learning disability and aggressive tendencies. We identified a deleterious nonsense mutation, c.1807C>T (p.Q603Ter), in exon 12 of the SYN1 gene (NM_006950), which can result in a truncated SYN1 phosphoprotein with altered flexibility and hydropathicity. This novel mutation has not been reported in the 1000G, EVS, ExAC, gnomAD, or HGMD databases. We identified a novel X-linked SYN1 exon 12 mutant gene in a Chinese family with toothbrushing epilepsy. Our findings provide novel insights into the mechanism of this complex form of reflex epilepsy that could potentially be applied in disease diagnosis.

In the field of particle therapy, the method of pencil beam scanning is of great potential for clinical application, now and in the future. The authors made strong effort to develop a spot scanning system for Shanghai Proton Therapy Facility. Design parameters and basic layout of the system are introduced. Functionalities and specifications of crucial devices are described in detail. Most of the devices in the system were designed in house by the authors themselves, including scanning nozzle, scanning magnets and their power supplies, beam monitors, irradiation control modules and safety interlock modules. During the technical commissioning stage in the fix beam room, the spot scanning system was tested and verified. Under conditions of the maximum dose rate and minimum dose rate, a) repeatability of the single spot dose is less than ± 0.1%; b) nonlinearity of the single spot dose is less than ± 0.1%; c) FWHM for spot size in air at isocenter varies from 8mm to 12mm for full energy, consistent with the design values; d) lateral dose distribution achieves a flatness of less than 2% for multiple proton energies. According to the results of technical commissioning, the spot scanning system is capable of producing a prescribed 3D dose distribution for target tumor successfully.

Objective: To investigate thyroid-stimulating hormone (TSH) levels and thyroid peroxidase antibody (TPOAb) in early pregnancy and to estimate the risk of development of gestational diabetes mellitus (GDM). Methods: The levels of TSH, free thyroxine, free triiodothyronine, and TPOAb were retrospectively evaluated in 2333 pregnant women. All women recruited were divided into groups of TSH high (H), TSH low (L), TSH (H) TPOAb positive (+), TSH (H)TPOAb negative (－), TSH normal (N)TPOAb (+), TSH (L)TPOAb (+), TSH (L)TPOAb (－), and estimated the risk of GDM. Results: TSH level (X2=13.0024, P= 0.0015) and TSH combined TPOAb (X2=20.0038, P= 0.0012) were correlated to development of GDM. The level of TSH in 95 women was increased, and in 216 women were decreased. Of the 2333 pregnant women, 546 patients were diagnosed with GDM, with a prevalence of 23.40%. The prevalence of GDM was 35.78% and 28.70% for the TSH high (H) and TSH low (L) pregnant women, respectively. The increased TSH (P= 0.0013, odds ratio: 2.09, confidence interval:1.34-3.28) was correlated to increase GDM incidence. TSH (H) TPOAb (+) (n = 29), TSH (H) TPOAb (－) (n = 58), TSH normal(N) TPOAb (+) (n= 265), TSH (L) TPOAb (+) (n= 30), TSH (L) TPOAb (－) (n = 154) were in this study. The prevalence of GDM was 51.72%, 29.31%, 23.02%, 26.67%, and 29.87% for the TSH (H) TPOAb (+), TSH (H) TPOAb (－), TSH (N) TPOAb (+), TSH (L) TPOAb(+), and TSH (L) TPOAb (－) pregnant women, respectively. Only the TSH (H) TPOAb (+) pregnant women had a significant higher incidence of GDM (P= 0.0018, odds ratio: 3.63, confidence interval: 1.62-8.16). Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb. Conclusion: Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM. Key words: Diabetes, gestational; Thyrotropin; Pregnancy trimester, first; Pregnancy trimester, second

Xin-Ying Li,1 Shuang Yao,1 Yang-Ting He,1 Song-Qing Ke,1 Yi-Fei Ma,2 Ping Lu,3 Shao-Fa Nie,1 Shao-Zhong Wei,2 Xin-Jun Liang,3 Li Liu1 1Department of Epidemiology and Biostatistics, The Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Gastrointestinal Oncology Surgery, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Department of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Li LiuDepartment of Epidemiology and Biostatistics, the Ministry of Education Key Laboratory of Environment and Health, School of Public Health, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-83693763Email liul2012@hust.edu.cnXin-Jun LiangDepartment of Abdominal Oncology, Hubei Cancer Hospital, The Seventh Clinical School Affiliated of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaTel/Fax +86-27-87671663Email doctorlxj@163.comPurpose: This study was designed to investigate the prognostic value of the combination of high-sensitivity C-reactive protein, lymphocyte, and albumin in patients with resectable colorectal cancer.Patients and Methods: Seven-hundred-and-nineteen patients who underwent colorectal cancer resection in Hubei Cancer Hospital were included. Inflammation-Immunity-Nutrition score (0– 6) was constructed based on preoperative high-sensitivity C-reactive protein, lymphocyte, and albumin. Time-dependent receiver operating characteristic curve, decision curve, Kaplan-Meier survival curve, Cox regression, and C-index were conducted to detect the prognostic values of inflammation-immunity-nutrition score. The prognostic values of inflammation-immunity-nutrition score in different subgroups by sex, location of tumor, pathologic stage, and KRAS mutation were also explored. The prognostic performance of inflammation-immunity-nutrition score was further compared with that of other traditional prognostic indicators.Results: The median follow-up time was 40 months. High inflammation-immunity-nutrition score (> 2 scores) presented worse survival, with the adjusted hazard ratios (95% confidence intervals) of 3.106 (2.202– 4.380) for overall survival and 2.105 (1.604– 2.764) for disease-free survival. Besides, the associations of high inflammation-immunity-nutrition score with overall survival were even stronger in cases with wild type KRAS, with the adjusted hazard ratios (95% confidence intervals) of 4.018 (2.355– 6.854). Considering the AUCs, C-indices, and hazard ratios estimates, inflammation-immunity-nutrition score presented better prognostic performance than high-sensitivity modified Glasgow prognostic score, high-sensitivity C-reactive protein to albumin ratio, prognostic nutrition index, carcinoembryonic antigen, and carbohydrate antigen 19-9 for overall survival.Conclusion: Inflammation-immunity-nutrition score might serve as a powerful prognostic score in patients with colorectal cancer for overall survival, particularly in patients with wild type KRAS.Keywords: high-sensitivity C-reactive protein, survival, colorectal cancer, inflammation

Butelase-1 is an efficient ligase from Clitoria ternatea with wide applications in the food and biopharmaceutical fields. This research aimed to achieve high-efficiency expression of butelase-1 and explore its application in food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides. The recombinant butelase-1 zymogen was prepared at a yield of 100 mg/L in Escherichia coli and successfully activated at pH 4.5, resulting in a 6973.8 U/L yield of activated butelase-1 with a specific activity of 348.69 U/mg and a catalytic efficiency of 9956 M-1 s-1. Activated butelase-1 exhibited considerable resistance to Tween-20, Triton X-100, and methanol. The "traceless" cyclization of ACE inhibitory peptides was realized using activated butelase-1, which resulted in higher stability and ACE inhibitory activity than those of the linear peptides. Our work proposed an efficient method for the preparation of butelase-1 and provided a promising model for its application in food fields.

Objective: The objectives of this study were to compare the risk and timing of seizure relapse in seizure-free patients with epilepsy following the withdrawal of monotherapy or polytherapy and to identify relevant influencing factors.Methods: Patients who had achieved at least a 2-year seizure remission and started the withdrawal of antiseizure medication (ASM) were enrolled in this study. All patients were followed for at least 3 years or until seizure relapse. According to the number of ASMs at the time of withdrawalwas about twice than that, patients were divided into two groups: monotherapy group and polytherapy group. The Cox proportional hazards model was used to compare the recurrence risk of the two groups. Univariate analysis and multiple logistic regression analysis were used to analyze potential confounding variables between patients treated with monotherapy and polytherapy.Results: A total of 188 patients (119 males and 69 females) were included. The average prescribed daily dose of most ASMs at the time of withdrawal was moderate or low (30–50% defined daily dose). The recurrence of most patients (89.2%) occurred within the first 3 years after withdrawal. The recurrence risk in patients treated with polytherapy at the time of withdrawal was about twice than that of the monotherapy group [p = 0.001, hazard ratio (HR) = 2.152, 95% confidence interval (CI) = 1.350–3.428]. Multivariate analysis showed that patients treated with polytherapy were significantly older at seizure onset [p = 0.024, odd ratio (OR) = 1.027, 95% CI = 1.004–1.052] and had a significantly longer duration of epilepsy before treatment (p = 0.004, OR = 1.009, 95% CI = 1.003–1.015) compared to patients in the monotherapy group. In addition, a history of perinatal injury was found to be an independent risk factor of seizure relapse in patients with ASM withdrawal.Conclusion: The average prescribed daily dose of most ASMs at the time of withdrawal was moderate or low. Patients who received polytherapy at the time of withdrawal, particularly those with later seizure onset age and longer epilepsy duration before treatment, had a higher recurrence risk after ASMs withdrawal compared to patients treated with monotherapy.

An amendment to this paper has been published and can be accessed via the original article.

Background Development and progression of HBV-related acute-on-chronic liver failure (HBV-ACLF) are associated with inflammatory responses. We aimed to explore the utility of blood cell count-derived inflammatory markers (white blood cell, neutrophil-to-lymphocyte ratio, red cell distribution width, and monocyte-to-lymphocyte ratio [MLR]) as prognostic index in HBV-ACLF patients. Methods A total of 160 HBV-ACLF patients were included in this retrospective study. Univariate and multivariate analyses were performed to identify predictors of poor outcomes, and the performance of these predictors was evaluated by receiver operating characteristic curve analysis. Results Fifty-six patients died within 28 days after admission. MLR was markedly higher in non-survivors than in survivors. Moreover, MLR was an independent predictor for 28-day mortality. Conclusions This retrospective study found that MLR is a simple and accurate prognostic index for mortality in HBV-ACLF patients and can serve as a screening tool for prediction of poor outcomes in these patients.

Background and aims It has been reported that Helicobacter pylori (HP) infection was more prevalent in infertile populations. HP infection could lead to decreased sperm parameters, and treating the HP infection could improve the quality of sperm. However, studies investigating the relationship between infertility and HP infection are still limited, and more evidence is required. Therefore, we performed the present study to investigate the impact of HP infection on sperm quality in males and on ovarian reserve in females. Methods A total of 16,522 patients who visited the Second Hospital of Zhejiang University from January 2016 to June 2019 due to abdominal discomfort and underwent a 13/14C-urea breath HP test were included in this retrospective cross-sectional study. Among them, 565 had performed sperm analysis or ovarian reserve tests in the past three months and were involved for further analyses. Sperm parameters were examined with a computer-assisted sperm analysis system, and serum anti-Müllerian hormone (AMH) and sex hormones were tested with an electrochemiluminescence method. Results Among 363 patients who underwent the sperm test, 136 (37.47%) had HP infection. Among 202 patients who underwent the AMH test, 55 (27.23%) had HP infection. There was no difference in sperm concentration and motility between the HP+ and HP− groups (P > 0.05). Further subgroup analyses stratified into 5-year age groups confirmed that there was no significant difference in sperm parameters (P > 0.05). When pooled with previously published data, no significant difference in sperm concentration or motility was found (P > 0.05). Meanwhile, this study found that the serum AMH level was similar between the HP+ and HP− groups (P > 0.05). Further subgroup analyses confirmed that there was no significant difference in serum AMH level (P > 0.05). Conclusions There were no differences in sperm parameters and AMH levels based on history of HP infection among Chinese patients.

Background A worldwide outbreak of coronavirus disease 2019 (COVID-19) has drawn global attention. However, up to now, no standard and effective therapy are available. Case presentation A 62-year-old man with a history of hypertension and diabetes was diagnosed with COVID-19 pneumonia. He suffered from obvious shortness of breath and severe hyoxemia. Normal treatments like supportive therapy and antiviral drugs didn’t seem to improve his conditions. Then, he was given tocilizumab and human umbilical cord mesenchymal stem cells. After that, his respiratory symptoms and lung infectious lesions gradually subsided, and he was successfully discharged eventually. Conclusions For critically ill COVID-19 patients, immunological treatment like tocilizumab human umbilical cord mesenchymal stem cells should be considered.

Background Anti-Müllerian hormone (AMH) is now considered the best serum biomarker of ovarian reserve, while basal sex hormones are classic markers used for assessing ovarian reserve. The interaction between AMH and sex hormones are complicated and not sufficiently addressed. In this study, we took diminished ovarian reserve (DOR) and polycystic ovarian syndrome (PCOS) as two extremes of ovarian reserve (deficient and excessive respectively) to investigate the role of AMH and sex hormones in follicular growth. Methods A retrospective cross-sectional survey was performed. The patients assessed AMH and basal sex hormones in the Second Hospital of Zhejiang University from April 2016 to March 2019 were involved in this study. Serum AMH and sex hormone concentrations were tested with electrochemiluminescence method. Stepwise linear regression and binary logistic regression was used to determine the predictors of AMH level and to explore the involved factors determining DOR and PCOS. Results In the present study, we found that age and follicle-stimulating hormone (FSH) were main negative correlation factors, and luteinizing hormone (LH) and testosterone (T) were main positive factors of AMH. In DOR group, age, FSH and estradiol (E2) increased and T decreased, while in PCOS group, LH and T increased. Binary logistic regression found that age, weight, FSH, E2, and T were the significant factors which independently predicted the likelihood of DOR, and that age, body mass index (BMI), AMH, LH, and T predicted the likelihood of PCOS. Conclusions Our study demonstrated that age, FSH, and T were factors that most closely correlated with AMH level, and T was involved in both DOR and PCOS. Since DOR and PCOS are manifested with insufficient AMH and excessive AMH respectively, it is suggested that total testosterone correlated with AMH closely and plays an important role in follicular growth. More attention should be given to testosterone level during controlled ovarian hyperstimulation (COH) process.

The purpose of this study was to identify and compare the diagnostic performance of gadolinium-ethoxybenzyl-diethyltriethylenetriacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) in hepatocellular carcinoma (HCC). Two researchers searched PubMed, EMBASE, and Cochrane Library databases from the inception of each database to 10 February 2020, to find comparative studies of Gd-EOB-DTPA-MRI and CEUS in detection of HCC. The study included eight studies (374 patients). MRI is superior to CEUS in diagnostic sensitivity of HCC, P = .03. The diagnostic sensitivity of MRI in lesions with a diameter of less than 30 mm was significantly higher than that of CEUS, P = .04. MRI and CEUS had no significant difference in diagnostic specificity of HCC, P = .95. Summary Receiver Operating Characteristics (SROC) of MRI showed a larger than that of CEUS, but with P > .05. Gd-EOB-DTPA-MRI showed higher sensitivity than CEUS for hepatocellular carcinoma lesions, especially for lesions of less than 30 mm across.

Background: Robot-assisted and laparoscopic surgery are the most minimally invasive surgical approaches for the removal of liver lesions. Minor hepatectomy is a common surgical procedure. In this study, we evaluated the advantages and disadvantages of robot-assisted vs laparoscopic minor hepatectomy (LMH). Methods: A systematic literature search was performed in PubMed, Embase, and the Cochrane Library to identify comparative studies on robot-assisted vs. laparoscopicminor hepatectomy up to February, 2020. The odds ratios (OR) and mean differences with 95% confidence intervals were calculated using the fixed-effects model or random-effects model. Results: A total of 12 studies involving 751 patients were included in the meta-analysis. Among them, 297 patients were in the robot-assisted minor hepatectomy (RMH) group and 454 patients were in the LMH group. There were no significant differences in intraoperative blood loss (P = .43), transfusion rates (P = .14), length of hospital stay (P > .64), conversion rate (P = .62), R0 resection rate (P = .56), complications (P = .92), or mortaliy (P = .37) between the 2 groups. However, the RMH group was associated with a longer operative time (P = .0003), and higher cost (P

Problem The effect of thyroid autoimmunity (TAI) on the prevalence of recurrent miscarriage (RM) is highly debatable. No meta‐analysis has been published in the past decade to investigate the impact of TAI on women with RM. Method of Study Systemic literature search was conducted on PubMed, Embase, Cochrane, and Web of Science databases. English language literatures published between 1993 and 2019 were selected. We assessed the relationship between the prevalence of RM and thyroid peroxidase antibodies (TPO‐Ab) or antithyroid antibodies (ATA) and evaluated the thyroid‐stimulating hormone (TSH) level in TPO‐Ab‐positive women with RM. We also observed the treatment effect with levothyroxine (LT4) for RM. Review Manager 5.3 software was used to obtain the pooled odds ratios (OR). Results Analysis of 22 eligible studies revealed significant association between TPO‐Ab and the prevalence of RM (OR = 1.85; 95% CI, 1.38 to 2.49; P, This study reveals the association between thyroid autoimmunity and TSH level, the prevalence of RM. And LT4 supplementation may effectively increase live birth rate.

Overexpression of ANXA1 and EphA2 has been linked to various cancers and both proteins have attracted considerable attention for the development of new anticancer drugs. Here we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination and degradation in nasopharyngeal carcinoma (NPC). Binding of ANXA1 to EphA2 promoted NPC cell growth and metastasis in vitro and in vivo by elevating EphA2 levels and increasing activity of EphA2 oncogenic signaling (pS897-EphA2). Expression of ANXA1 and EphA2 was positively correlated and both were significantly higher in NPC tissues than in the normal nasopharyngeal epithelial tissues. Patients with high expression of both proteins presented poorer disease-free survival and overall survival relative to patients with high expression of one protein alone. Furthermore, amino acid residues 20-30aa and 28-30aa of the ANXA1 N-terminus bound EphA2. An 11 amino acid–long ANXA1-derived peptide (EYVQTVKSSKG) was developed on the basis of this N-terminal region, which disrupted the connection of ANXA1 with EphA2, successfully downregulating EphA2 expression and dramatically suppressing NPC cell oncogenicity in vitro and in mice. These findings suggest that ANXA1 promotes NPC growth and metastasis via binding and stabilization of EphA2 and present a strategy for targeting EphA2 degradation and treating NPC with a peptide. This therapeutic strategy may also be extended to other cancers with high expression of both proteins. Significance: These findings show that EphA2 is a potential target for NPC therapeutics and an ANXA1-derived peptide suppresses NPC growth and metastasis.

Ethnopharmacological relevance Rheum palmatum L; Astragalus membranaceus (Fisch.), is referred to as ‘Dahuang, Huangqi’ in China. As an important medicinal plant, the rhizome of rhubarb and astragalus is traditionally used in the treatment of kidney diseases associated with renal failure, inflammation and tumors. Aim of the study: This study aimed to investigate the effect of a drug-containing serum of rhubarb-astragalus capsules (composed of rhubarb and astragalus) and to elucidate its mechanism in the epithelial-mesenchymal transformation of renal tubular epithelial cells. Materials and methods Epithelial-mesenchymal transformation (EMT) of HK-2 cells was induced by TGF-β1, and rhubarb-astragalus and losartan drug-containing serum from rats, as well as SB203580 (a specific inhibitor of p38 MAPK), were used. High-performance liquid chromatography analysis was performed to determine the main components of the drug-containing serum of rhubarb-astragalus from rats. Western blotting and immunofluorescence analysis were used to determine the levels of protein expression, and real-time quantitative PCR analysis was used to detect the levels of gene expression. Results The drug-containing serum of rhubarb-astragalus contained emodin (0.36 μg/ml) and danthraquinone (0.96 μg/ml). Rhubarb-astragalus significantly decreased the protein expression levels of α-SMA, FN, vimentin and N-cadherin in HK-2 cells that were increased by TGF-β1, while it significantly increased the E-cadherin protein expression level that was decreased by TGF-β1. Rhubarb-astragalus also significantly decreased the protein expression levels of TGF-β1 and p38 MAPK and the mRNA expression levels of α-SMA, vimentin, TGF-β1, p38 MAPK, Smad2 and Smad3 in HK-2 cells that were increased by TGF-β1. It is worth noting that SB203580 (a p38 MAPK inhibitor) had similar effects as rhubarb-astragalus in this study. Conclusion The drug-containing serum of rhubarb-astragalus can inhibit EMT in HK-2 cells by downregulating the TGF-β1/p38 MAPK/Smad2/3 pathway.

This study investigated the long-term response and response patterns to antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy.Patients who had been newly diagnosed with epilepsy and had at least 3-year follow-up records were enrolled. Their long-term response and response patterns to AEDs were retrospectively analyzed. Patients were divided into two groups, a controlled group and an uncontrolled group, according to whether 3-year seizure freedom (3YSF) was achieved. Multiple logistic regression analyses were used to identify risk factors associated with a poor drug response.Of the 472 patients with epilepsy, 180 achieved immediate seizure control, 36 achieved early seizure control, 118 achieved late seizure control, and 138 did not achieve 3YSF. Patients who achieved 3YSF (334/472, 70.8%) were categorized into the controlled group. Among them, 53.9% (180/334) achieved 3YSF immediately, 10.8% (36/334) achieved 3YSF within 6 months, and 35.3% (118/334) achieved 3YSF after 6 months. Also in this group, 228 (228/472, 48.3%), 84 (84/472, 17.8%), 15 (15/472, 3.2%), and 7 (7/472, 1.5%) patients achieved 3YSF on the first, second, third, and fourth regimen, respectively. Multivariate analyses showed that multiple seizure types (odds ratio [OR] = 3.903, 95% confidence interval [CI]: 2.098-7.264; P 0.001] and polytherapy (OR = 5.093, 95% CI: 3.183-8.149; P 0.001) were independent risk factors for a poor drug response.The 3YSF rate in this cohort was 70.8%. More than half of the patients achieved long-term remission immediately after treatment. The probability of attaining 3YSF decreased with the increase in number of drug regimens, especially in patients who experienced failure of two treatment regimens.

A chitinase gene (RmChiA) encoding 445 amino acid (aa) residues from a fungus Rhizomucor miehei was cloned and overexpressed in Escherichia coli. Two kinds of RmChiA crystal forms, with space groups P32 2 1 and P1, were obtained by sitting-drop vapor diffusion and the structures were determined by X-ray diffraction. The overall structure of RmChiA monomer, which is the first structure of bacterial-type chitinases from nonpathogenic fungi, adopts a canonical triosephosphate isomerase (TIM) barrel fold with two protruding chitinase insertion domains. RmChiA exhibited a unique NxDxE catalytical motif and a real active site tunnel structure, which are firstly found in GH family 18 chitinases. The motif had high structural homolog with the typical DxDxE motif in other GH family 18 chitinases. The tunnel is formed by two unusual long loops, containing 15 aa and 45 aa respectively, linked by a disulfide bond across the substrate-binding cleft. Mutation experiments found that opening the roof of tunnel structure increased the hydrolysis efficiency of RmChiA, but the thermostability of the mutants decreased. Moreover, the tunnel structure endowed RmChiA with the exo-chitinase character.

Cisplatin (CDDP) may induce apoptosis of renal tubular epithelial cells (RTEC) and cause CDDP-induced acute kidney injury (CAKI) during cancer treatment, but yet lack of preventive measures and effective treatment. As a new Chinese herbal preparation, Panax notoginseng saponins (PNS) has been found to mitigate CDDP-induced CAKI through elevating the expression of HIF-1α in the rat model, according to the data from our previous works. However, the underlying link between HIF-1α and apoptosis has not been well elucidated. The current study as a follow-up work, was aimed to reveal if PNS improves CAKI through HIF-1α-dependent apoptosis. A stably HIF-1α-knockdown human proximal tubular epithelial cell (HK-2) line was established by transfecting a HIF-1α-siRNA into HK-2 cells. Cell viability, mitochondrial function, cell apoptosis ratio and the expression of apoptosis-associated proteins (Cyt C, Bcl2, Bax, caspases 3) were determined. In order to elucidate the underlying mechanism, the expression of HIF-1α and BNIP3 were assessed. Our results showed that treatment of PNS rescued the cell viability of CDDP-injured HK-2 or HIF-1α-knockdown HK-2 cells, and increased the expression levels of ATP and MMP in HK-2 or HIF-1α-knockdown HK-2 cells which were reduced by CDDP. Moreover, PNS treatment decreased the CDDP or CDDP plus HIF-1α-knockdown-induced elevation of apoptosis and apoptosis-associated protein expressions. These findings demonstrate that PNS reduces CAKI through increasing HIF-1α to inhibit mitochondrial apoptosis pathway. Hence, we suggest PNS as a protective and therapeutic new drug for CDDP treatment of cancers, which might have significant meaning of further research and application potential.

In this report, we collected the Raman spectrum of cervical adenocarcinoma and cervical squamous cell carcinoma tissues by a micro-Raman spectroscopy system. We analysed, compared and summarized the characteristics and differences of the normalized mean Raman spectra of the two tissues and pointed out the major differences in the biochemical composition between the two tissues. The PCA-SVM model that was used to distinguish the two types of cervical cancer tissues was established. The accuracy of the model in differentiating cervical adenocarcinoma from cervical squamous cell carcinoma was 93.125%. The results of this study indicate that Raman spectroscopy of cervical adenocarcinoma and cervical squamous cell carcinoma tissue in combination with SVM (support vector analysis) and PCA (principal component analysis) can be useful for the classification of cervical adenocarcinoma and cervical squamous cell carcinoma tissues and for the exploration of the differences in biochemical compositions between the two types of cervical tissue. This study lays a foundation to further study Raman spectroscopy as a clinical diagnostic method for cervical cancer.

ANXA1 and EphA2 play a crucial role in cancer. Here, we report that ANXA1 competes with Cbl for binding EphA2 and increases its stability by inhibiting Cbl-mediated EphA2 ubiquitination degradation in nasopharyngeal carcinoma (NPC), leading to the enhanced NPC growth and metastasis in vitro and in vivo . In human NPC, patients with the high expression of both ANXA1 and EphA2 proteins have poorer disease-free survival and overall survival relative to patients with the high expression of one protein alone. Furthermore, based on the N-terminal amino acid 20-30 region of ANXA1 responsible for binding EphA2, we develop an ANXA1-derived peptide, named as A1 (20-30), that cuts its connection with EphA2, successfully downregulates EphA2 and suppresses NPC oncogenicity in vitro and in vivo. These findings reveal that ANXA1, via binding and stabilizing EphA2, drives NPC growth and metastasis, and present a strategy for targeting EphA2 degradation and treating NPC with a peptide.

It is stated that high expression of pyruvate kinase (PKM2) emerges as a significant player in the metabolism and progression of various human malignancies. However, the expression of PKM2 and its association with the prognosis of osteosarcoma had not yet been studied. In the present study, the expression and biological significance of PKM2 in osteosarcoma were investigated. We found that PKM2 expression was elevated in the cancerous tissues and it was more abundant than the adjacent normal tissues (60.2 vs 26.1 %, p

The aim of this study was to investigate the differentiation potential of induced pluripotent stem cells (iPSCs) derived from human foreskin fibroblasts (HFFs) into hepatocyte-like cells (HLCs). The iPSCs were firstly induced by transduction of OCT4, SOX2, KLF4, and c-MYC into HFFs using retrovirus. Afterwards, expressions of pluripotency factors were identified by semiquantitative reverse transcription–polymerase chain reaction and immunofluorescence staining, and karyotype, embryoid, and teratoma were observed by microscope. Then, iPSCs were gradually differentiated into endoderm cells, hepatic progenitor cells, and mature HLCs by special culture medium. During this process, differentiation efficiency into each kind of cells was evaluated by detecting SOX17, HNF4a, and ALB using flow cytometry, respectively. Besides, enzyme-linked immunosorbent assay was conducted to detect the secretion of ALB in iPSC-induced HLCs and quantitative reverse transcription–polymerase chain reaction was performed to detect the expression levels of hepatocyte-specific genes. The iPSCs were successfully induced by HFFs, which exhibited typical embryonic stem cells morphology, positive alkaline phosphatase staining, normal diploid karyotype, and positive expression of various pluripotency factors. Meanwhile, spherical embryoid and teratoma with 3 germ layers were formed by iPSCs. The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells and mature HLCs, and the differentiation efficiency was 55.7 ± 2.9%, 45.7 ± 4.8%, and 35.0 ± 3.9%, respectively. Besides, the secretion of ALB and expression of various hepatocyte-specific genes was highly detected in iPSC-induced HLCs. The iPSCs were successfully derived from HFFs and then differentiated into HLCs, which proved a new source for hepatocyte transplantation. Highlights HFFs were successfully induced into iPSCs by transduction of OCT4, SOX2, KLF4, and c-MYC. Positive expressions of various pluripotency factors were exhibited in HFFs-induced iPSCs. The iPSCs were consecutively induced into endoderm cells, hepatic progenitor cells, and mature HLCs. Various hepatocyte-specific genes were highly expressed in iPSC-induced HLCs.

Summary Adenosine deaminase (ADA) inhibitors regulate cellular levels of adenosine and deoxyadenosine and can be used as anti-inflammatory and anticancer drugs or degradation inhibitors of adenosine drugs. Screening of natural ADA inhibitors indicated crude extracts from Tofu wastewater and litchi peel showed strong ADA inhibition. Genistin, genistein and daidzein from Tofu wastewater and cyanidin-3-rutinoside from litchi peel were purified with simple processes and identified as ADA inhibitors. Structure–activity investigation indicated genistein and cyanidin-3-rutinoside had high ADA inhibition at IC50 of 0.4 and 0.6 mg mL−1, respectively. Genistein and cyanidin-3-rutinoside showed synergistic anticancer and antibacterial activities with cordycepin. Docking simulation suggested that genistein and cyanidin-3-rutinoside can enter into ADA active site, bind with its functional amino acids through H-bonds and competitively inhibit the enzyme. This work indicated the extracts from Tofu wastewater and litchi peel, and their active flavonoids from food processing wasters can be used as health food.

Objective Hepatitis B virus (HBV) infection causes liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC) development, but the underlying mechanism remains poorly understood. This study aimed to investigate the roles and molecular mechanisms of Dystrobrevin-α (DTNA) in HBV-induced liver cirrhosis and HCC pathogenesis. Methods DTNA expression was bioinformatically analyzed using the GEO database. DTNA expression was silenced by transfection with shRNAs. Cell proliferation and apoptosis were evaluated by MTT and flow cytometry respectively. The expression of genes in mRNA or protein levels was assessed by quantitative RT-PCR and western blotting. The interaction between proteins was predicted with the String and GCBI online softwares, and then confirmed by co-immunoprecipitation. Animal models were established by injecting nude mice with AVV8-HBV1.3 vector. Results Bioinformatics analysis showed a significantly increase in DTNA expression in HBV-positive liver cirrhosis and HCC patients. HBV infection caused a significantly increase in DTNA expression in HCC cell lines HepAD38 and HepG2.2.15. DTNA knockdown suppressed proliferation and promoted apoptosis of HBV-infected HepAD38 and HepG2.2.15 cells. HBV induced elevated expression of fibrosis-related genes Collagen II and TGFβ1 in LO-2 cells, which were suppressed by DTNA knockdown. DTNA directly binded with STAT3 protein to promote STAT3 phosphorylation and TGFβ1 expression and repress P53 expression in HBV-infected HepAD38 and LO-2 cells. The DTNA/STAT3 axis was activated during HBV-induced fibrosis, cirrhosis and HCC development in mouse model. Conclusion DTNA binds with and further activates STAT3 to induce TGFβ1 expression and repress P53 expression, thus promoting HBV-induced liver fibrosis, cirrhosis and hepatocellular carcinoma progression.

We performed observational cohort study to compare the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC), lamotrigine (LTG), and levetiracetam (LEV) monotherapy for newly diagnosed focal epilepsy patients.Three hundred and eighty eight newly diagnosed focal epilepsy patients aged 1-70 years were enrolled in this study between June 2009 and March 2016. Among the patients, 191 were treated with OXC, 98 were treated with LTG, and 99 were treated with LEV monotherapy. The study was performed in a real-world setting and the primary outcomes were the one-year and three-year seizure-free rates. The secondary outcomes were the one-year and three-year withdrawal rates, the time to treatment withdrawal, the time to the first seizure, and the time to achieve one-year remission.The three-year seizure-free rates with LTG (39.8 %) and LEV (41.4 %) were significantly better than that with OXC (26.2 %) (both P 0.05). However, no significant difference was observed among the three drugs for the one-year seizure-free rate. The three-year withdrawal rate was 50.8 %, 46.9 %, and 43.4 % for OXC, LTG, and LEV, respectively (all P 0.05). The one-year withdrawal rate for OXC (31.7 %) was higher than those for LTG (30.6 %) and LEV (26.3 %) (all P 0.05). LEV [Relative Risk (RR) = 0.69, 95 % CI: 0.49∼0.99] and LTG (RR = 0.63, 95 % CI: 0.44∼0.9) were significantly better than OXC in preventing first seizure. LEV appears to be the superior option with regard to the time to achieve one-year remission.The results of the study showed that LEV and LTG are significantly more effective than OXC for the treatment of newly diagnosed focal epilepsy. LEV has milder adverse events than OXC and LTG in clinical practice.

Objective This study aimed to investigate the long-term outcome in seizure-free patients and to explore the risk factors of seizure relapse following antiepileptic drug (AED) withdrawal. Methods This study included 161 patients who had been seizure-free for at least 2 years. These patients were monitored over a follow-up period of at least 3 years or until seizure relapse after AED withdrawal. Patients were grouped into a seizure-free group and a relapse group. Risk factors of seizure relapse were analyzed. Results During the follow-up period, 72 patients (44.7%) relapsed while 89 patients (55.3%) did not. The average time of relapse was 19.12 ± 27.17 months after the initiation of AED withdrawal, and majority of cases occurred within the first 24 months of AED withdrawal (73.6%). Univariate analysis showed that the likelihood of relapse was higher in patients with uncontrolled seizures beyond the first 6 months of AED therapy initiation, patients with a history of perinatal injury, patients with multiple seizure types, and patients who had been treated with a combination of AEDs. Multiple logistic regression analysis revealed that uncontrolled seizures beyond the first 6 months of AED treatment and a history of perinatal injury were independent risk factors of seizure relapse. Conclusion In the majority of cases, epilepsy relapse occurred within the first two years after the initiation of AED withdrawal. The independent risk factors of seizure relapse were uncontrolled seizures beyond the first 6 months of AED therapy and cases with a history of perinatal injury.

Phosphatidylethanolamine (PE)-binding protein 4 (PEBP4) is an antiapoptotic protein that is aberrantly expressed in various malignancies. We previously demonstrated that PEBP4 expression is dramatically induced in human gliomas and positively correlated with tumor grade and patient survival. However, the function of PEBP4 in human glioma development and underlying mechanisms remain largely unknown. By stable lentiviral vector-mediated silencing of PEBP4, we examined the effects of PEBP4 knockdown on the growth, apoptosis, and invasion of U251 and U373 human glioma cell lines using MTT, Transwell, colony formation, and flow cytometric assays. We examined the in vivo role of PEBP4 in tumor growth by inoculation of BALB/c nu/nu male mice with PEBP4-deficient U251 and U373 cells. The expression of cell cycle- and apoptosis-related proteins was analyzed by Western blotting and immunostaining. Knockdown of PEBP4 significantly reduced the proliferation and invasion of human glioma cells while inducing cell apoptosis by altering the expression of cell cycle- and apoptosis-related proteins. Mechanistically, PEBP4 knockdown led to activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) pathway, an effect that could be reversed by U0126, a selective inhibitor of MEK1/2 (upstream of ERK1/2), suggesting involvement of ERK1/2 signaling in the regulation of glioma development and progression by PEBP4. We identified PEBP4 as a novel regulator mediating human glioma cell proliferation, invasion, and apoptosis as well as tumor formation and growth. Therefore, PEBP4 may be a potential therapeutic target in human glioma treatment.

Activation of proinflammatory cytokines in seizures has been well characterized. However, role of cytokines in epilepsy and association with different clinical phenotype has not been well investigated. Reports on possible link between proinflammatory molecules and epilepsy are very limited. In this study, we performed a hospital-based case control study to investigate the association of plasma cytokines and their expression with different clinical categories of epilepsy. Patients admitted to Neurology Department of Renmin Hospital were enrolled in this study after clinical investigations. In all, 92 patients with temporal lobe epilepsy (TLE) and 45 with extra-temporal lobe epilepsy (XTLE) were included in this study. Furthermore, we included 86 healthy controls from the similar geographical population. Plasma levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β were quantified by enzyme-linked immunosorbent assay (ELISA). All plasma cytokines were elevated in TLE and XTLE compared to healthy controls ( P

Lung cancer is the leading cause of cancer-associated mortality worldwide. Elucidation of the pathogenesis and biology of lung cancer is critical for the design of an effective treatment for patients. Non-small cell lung cancer (NSCLC) accounts for 80-85% of lung cancer cases. The abnormal expression of Notch signaling pathway members is a relatively frequent event in NSCLC. The Notch signaling pathway serves important roles in cell fate determination, proliferation, differentiation and apoptosis. Increasing evidence supports the association of Notch signaling dysregulation with various types of malignant tumor, including NSCLC. Several studies have demonstrated that members of the Notch signaling pathway may be potential biomarkers for predicting the progression and prognosis of patients with NSCLC. Furthermore, Notch signaling serves critical roles in the tumorigenesis and treatment resistance of NSCLC cells by promoting the proliferation or inhibiting the apoptosis of NSCLC cells. The present review provides a detailed summary of the roles of Notch signaling in NSCLC.

Background Erythropoietin (EPO) is a hypoxia-inducible stimulator of erythropoiesis. Besides its traditional application in anemia therapy, it offers an effective treatment in the cancer patients, especially those who receive chemotherapy. Several reports indicated that it could promote the tumor cell proliferation through its specific receptor (EPOR). Unfortunately, the role of EPO/EPOR in hepatocellular carcinoma (HCC) progressing is still uncertain. Methods Protein in tumor tissue from HCC patients or H22 tumor-bearing mice was detected with immunohistochemistry. Cells were cultured under 1% oxygen to establish hypoxia. RT-PCR and western blotting were used to measure mRNA and protein of EPO/EPOR, respectively. MTT, flow cytometry and PCNA staining were used to detect cell proliferation. Immunofluorescence staining was applied to study the expression and location of cellular EPOR. The EPOR binding studies were performed with 125I-EPO radiolabeling assay. Results EPO and EPOR protein were up-regulated in HCC tissue of patients and H22-bearing mice. These were positively correlated with hypoxia-inducible factor -1 α and ki-67. Hypoxia up-regulated the expression of EPO and EPOR in HepG2 cells. It also induced the proliferation and increased the percentage of divided cells after 24, 48 and 72 h treatment. These were inhibited in cells pre-treated with 0.5 μg/mL soluble-EPOR. Immunofluorescence staining presented that EPOR was obviously translocated from nucleus to cytoplasm and membrane under hypoxia. EPOR binding activity was also increased after exposure to hypoxia. Recombinant human erythropoietin obviously elevated cell proliferation rate and the percentage of divided under hypoxia but not normoxia, which were also inhibited by soluble-EPOR. Conclusions Our result indicated for the first time that EPO promoted the proliferation of HCC cells through hypoxia induced translocation of it specific receptor. Trial registration TJC20141113, retrospectively registered

ObjectivesTo assess the health-related quality of life (HRQOL) and willingness to pay (WTP) per quality-adjusted life-year (QALY) amount of patients with epilepsy in China.MethodsAdults with epilepsy and a healthy control were recruited in two tertiary hospitals in China. Participants completed two indirect utility elicitation instruments (Quality of Well-being Scale-self administered version and EuroQol five-dimensional questionnaire) and a WTP questionnaire. Correlations between sociodemographic or epilepsy-specific variables (age of epilepsy onset, duration of epilepsy, seizure types, types of antiepileptic drug treatment, etc.) and HRQOL or WTP/QALY were assessed to identify the candidate predictor. Multiple linear regression models were adopted to investigate the predictive performances of identified candidate predictors. Data analyses were performed on SPSS 20.0 (SPSS, Inc., Chicago, IL).ResultsFor utilities of both the Quality of Well-being Scale-self administered version and the EuroQol five-dimensional questionnaire, patients with epilepsy had statistically lower values than did the control group (P < 0.0001). In terms of the WTP/month, the percentage of WTP accounting for the monthly income and the WTP/QALY values from the epilepsy group were substantially higher than those from the control group (P < 0.0001).WTP/QALY=12×WTPMonth1−Utility(CurrentHealth)The multiple linear regression model identified working status (P = 0.05), seizure types (P = 0.022), income (P = 0.006), and self-rating health state (P < 0.05) as predictors of HRQOL while income (P = 0.000) and self-rating health state (P < 0.05) statistically contributed to the variations in WTP/QALY value for the epilepsy group.ConclusionsPatients with epilepsy had substantially lower HRQOL than did the healthy population.

OBJECTIVES: We aimed to gauge the burden of epilepsy in China from a societal perspective by estimating the direct, indirect and intangible costs. METHODS: Patients with epilepsy and controls were enrolled from two tertiary hospitals in China. Patients were asked to complete a Cost-of-Illness (COI), Willingness-to-Pay (WTP) questionnaires, two utility elicitation instruments and Mini Mental State Examination (MMSE). Healthy controls only completed WTP questionnaire, and utility instruments. Univariate analyses were performed to investigate the differences in cost on the basis of different variables, while multivariate analysis was undertaken to explore the predictors of cost/cost component. RESULTS: In total, 141 epilepsy patients and 323 healthy controls were recruited. The median total cost, direct cost and indirect cost due to epilepsy were US$949.29, 501.34 and 276.72, respectively. Particularly, cost of anti-epileptic drugs (AEDs) (US$394.53) followed by cost of investigations (US$59.34), cost of inpatient and outpatient care (US$9.62) accounted for the majority of the direct medical costs. While patients' (US$103.77) and caregivers' productivity costs (US$103.77) constituted the major component of indirect cost. The intangible costs in terms of WTP value (US$266.07 vs. 88.22) and utility (EQ-5D, 0.828 vs. 0.923; QWB-SA, 0.657 vs. 0.802) were both substantially higher compared to the healthy subjects. CONCLUSIONS: Epilepsy is a cost intensive disease in China. According to the prognostic groups, drug-resistant epilepsy generated the highest total cost whereas patients in seizure remission had the lowest cost. AED is the most costly component of direct medical cost probably due to 83% of patients being treated by new generation of AEDs.

5-Hydroxymethylfurfural (5-HMF) has been found widely in foods through degradation of hexoses and the Maillard reaction during heat treatment of foods containing reducing sugars and amino acids in an acid environment. We have previously demonstrated 5-HMF as an antioxidant and antiproliferative ingredient. However, the action mechanisms and the underlying signaling pathways remain elusive. Therefore, in this study, experiments were carried out to elucidate the molecular mechanisms accounting for the anticancer action of 5-HMF by using MTT assay, flow cytometric and Western blot analysis. The results showed that 5-HMF exhibited a dose-dependent inhibitory effect on A375 cells, which was caused by apoptosis and G0/G1 phase arrest. Meanwhile, exposure of phosphatidylserine was observed further to prove the cell apoptosis. Further investigation on the molecular mechanisms revealed that ROS acts as an upstream mediator in 5-HMF-induced A375 cell growth inhibition. Low levels of ROS can induce DNA damage-mediated expression of P53 and phosphorylates, mitochondrial dysfunction, G0/G1 arrest and the activation of AKT and MAPKs pathways, thereby contributing to apoptosis and G0/G1 phase arrest induced by 5-HMF. Our findings imply that 5-HMF may be a candidate chemopreventive and chemotherapeutic agent because the function that induces apoptosis and/or cell cycle arrest by many anticancer drugs in susceptible cells is also exhibited by 5-HMF.

Glutenins, which form the network of gluten protein, are of great importance for the quality of flour products. Glutenins can be divided into HMW and LMW subunits according to molecular weight. Three genes for LMW glutenin subunits (LMW-GS), named lmw-cnd1, lmw-cnd2, and lmw-cnd3 with open reading frames of 1,053, 903, and 969 bp, respectively, were cloned from wheat cultivar Cheyenne. Heterologous expression vectors of the three LMW-GS were constructed, and the recombinant proteins LMW-CND1, LMW-CND2, and LMW-CND3 were overexpressed in Escherichia coli. After cell disruption with ultrasound, target proteins of high purity were obtained by using Ni2+ affinity chromatography. Farinograph and TAPlus measurements were used to investigate the effects of the three LMW-GS on the characteristics of flour and dough. The results showed that the addition of each LMW-GS can lead to an increase in the elasticity of the dough. Moreover, LMW-CND2 and LMW-CND3 promoted the strength of the dough. All three LMW-G...

We aimed to develop and validate a Chinese version of the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG) for use in Chinese-speaking subjects internationally. Patients and healthy controls were recruited from two hospitals between July and October 2012. Receiver operating characteristic (ROC) curves were utilized to test criterion validity. Convergent validity was assessed via correlations between NUCOG and the Mini-Mental State Examination (MMSE). Reliability was measured by internal consistency (Cronbach's α). Patients with epilepsy (n=144), neurological diseases (n=81), dementia (n=44), and controls (n=260) completed the NUCOG and the MMSE. Overall, both NUCOG and MMSE scores differed significantly across the four groups with the highest scores in the control group and the lowest in the dementia group (p

5-HMF is widely presented in foods and produced through the degradation of hexoses and Maillard reaction during heat treatment of foods containing reducing sugars and amino acids in an acid environment. However, controversial conclusions on the biological effects of 5-HMF have been drawn in previous studies. Therefore, the main aim of this study was to investigate the antioxidant and antiproliferative activities of 5-HMF. The 2,2'-azinobis-3-ethylbenzothiazolin-6-sulfonic acid (ABTS) assay, the 1,1-diphenyl-2-picryhydrazyl (DPPH) assay, and the hemolysis assay induced by 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were performed to evaluate the antioxidant capacity of 5-HMF. The results showed that 5-HMF exhibited novel antioxidant activity by scavenging the ABTS and DPPH free radicals and inhibited the AAPH-induced hemolysis in a dose-dependent manner. In the hemolysis assay, the reduction of ROS and MDA contents and the increase in enzyme activities of SOD, CAT, and GPx were found in erythrocytes pretreated with 5-HMF, which demonstrated that 5-HMF could prevent the peroxidation from the source to protect the erythrocytes. The morphological changes of erythrocytes was also verified by observation using atomic force microscopy. The inhibitory effect of 5-HMF on human cancer cell proliferation was investigated by MTT assay, flow cytometric analysis, and the TUNEL and DAPI costaining assay. The results showed that 5-HMF displayed higher antiproliferative activity on human melanoma A375 cells than other cell lines. Further investigation on the action mechanisms revealed that 5-HMF could induce A375 cell apoptosis and G0/G1 cell cycle arrest. The A375 cell apoptosis that 5-HMF induced was characterized by a TUNEL and DAPI costaining assay. These findings suggest that 5-HMF could be developed as a novel natural antioxidant with potential applications in cancer chemoprevention.

Summary Purpose Generic preference-based health-related quality of life (HRQoL) instruments are increasingly used to estimate the quality-adjusted life years (QALYs) in cost-effectiveness/utility studies. However, no such tool has been used and validated in epilepsy patients in China. This study was conducted to validate a generic preference-based HRQoL instrument, namely the Quality of Well-Being Scale–Self-Administered (QWB-SA) in Chinese patients with epilepsy. Methods Accepted translation procedures were followed to develop the Chinese QWB-SA. An epilepsy group (adults with established diagnosis of epilepsy) and a control group (adults without manifested cognitive problems) were recruited between July and October, 2012, from two tertiary hospitals in China. After giving informed consent, each subject completed both the QWB-SA and the EuroQol (EQ-5D) as well as provided sociodemographic data. Construct validity was examined by six (convergent) and two (discriminative) a priori hypotheses. Sensitivity was compared by ability to differentiate epilepsy-specific variable-based subgroups. Agreement between the QWB-SA and EQ-5D was assessed by intraclass correlation coefficient (ICC) and Bland-Altman plot. Key Findings One hundred forty-four epilepsy patients and 323 control subjects were enrolled, respectively. The utility medians (interquartile range, IQR) for the QWB-SA and EQ-5D were 0.673 (0.172), 0.848 (0.275) for epilepsy group and 0.775 (0.258), 1.000 (0.152) for control group, respectively. The difference in utilities between the two measures were significant (p

A method was developed for simultaneous qualitative and quantitative analysis of five metabolites of nitrofuran antibiotics, including 3-amino-2-oxazolidinone (AOZ), 5-morpholino-methyl-3-amino-2-oxazolidinone ( AMOZ ), semicarbazide ( SEM ), 1-aminohydantoin (AHD) and 3, 5-dinitrosalicylic acid hydrazide (DNSH) in aquatic products by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The samples were hydrolyzed with HCl, and derivatized with 2-nitrobenzaldehyde at 37 degre C for 16 hours. The derivative solutions were adjusted to pH 7.0 -7. 5, and the analytes were extracted by ethyl acetate. The separation was based on Thermo Aquasil C18 column (150 mm x 4.6 mm, 3.01 micro m). The analytes were detected by tandem mass spectrometry with electrospray ionization source with multiple reaction monitoring (MRM) mode. The developed method showed good linear correlation between the peak area ratios of the analyte and the internal standard and the concentration of the analyte with the correlation coefficients all above 0. 99 over the dynamic range of 0.5 - 10 micro g/kg. The limits of quantitation (LOQs) of AOZ, AMOZ, SEM, AHD and DNSH were 0.5 micro g/kg. The average recoveries of all the compounds at four spiked levels of 0.5, 1.0, 2.0 and 4. 0 micro g/kg ranged from 81.3% to 100.5% with the RSDs between 3.4% and 10.0% (n =6). The method is proved to be fast and effective for simultaneous qualitative and quantitative analysis of the metabolites of the nitrofuran antibiotics in aquatic products.

Chang-Qing F, Yi L, De-Guang W, Qing-Bin S, Xiang-Min H, Na T, Jian-Hua L. Immune clearance gastric carcinoma cells in ascites by activating caspase-9-induced apoptosis. APMIS 2011; 119: 173–179. Floating gastric adenocarcinoma cells in ascitic fluid are the main cause of peritoneal dissemination. Activation of apoptosis is an important mechanism by which tumor cells are eliminated by the immune surveillance system. Hence, we examined caspase-9 expression and the apoptosis in gastric adenocarcinoma cells in ascitic fluid using immunohistochemistry, real-time polymerase chain reaction and in situ cell death detection kits, flow cytometry. The results revealed strong expression of caspase-9 in 58.49% (31/53) malignant cells and a relatively weak expression of caspase-9 in 41.51% (22/53) malignant cells. The proportion of apoptotic cells in 31 malignant cases with strong caspase-9 expression (35.14 ± 3.42)% was significantly higher than that in 22 malignant cases with relatively weak caspase-9 expression (17.29 ± 7.62)% or in mesothelial cells (10.76 ± 4.21%; p