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Oxidative stress contributes greatly to doxorubicin (DOX)-induced cardiotoxicity. Down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is a key factor in DOX-induced myocardial oxidative injury. Recently, we found that mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1)-dependent k48-linked ubiquitination was responsible for down-regulation of myocardial Nrf2 in DOX-treated mice. Micafungin, an antifungal drug, was identified as a potential MALT1 inhibitor. This study aims to explore whether micafungin can reduce DOX-induced myocardial oxidative injury and if its anti-oxidative effect involves a suppression of MALT1-dependent k48-linked ubiquitination of Nrf2. To establish the cardiotoxicity models in vivo and in vitro, mice were treated with a single dose of DOX (15 mg/kg, i.p.) and cardiomyocytes were incubated with DOX (1 μM) for 24 h, respectively. Using mouse model of DOX-induced cardiotoxicity, micafungin (10 or 20 mg/kg) was shown to improve cardiac function, concomitant with suppression of oxidative stress, mitochondrial dysfunction, and cell death in a dose-dependent manner. Similar protective roles of micafungin (1 or 5 μM) were observed in DOX-treated cardiomyocytes. Mechanistically, micafungin weakened the interaction between MALT1 and Nrf2, decreased the k48-linked ubiquitination of Nrf2 while elevated the protein levels of Nrf2 in both DOX-treated mice and cardiomyocytes. Furthermore, MALT1 overexpression counteracted the cardioprotective effects of micafungin. In conclusion, micafungin reduces DOX-induced myocardial oxidative injury via suppression of MALT1, which decreases the k48-linked ubiquitination of Nrf2 and elevates Nrf2 protein levels. Thus, micafungin may be repurposed for treating DOX-induced cardiotoxicity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Spinal Cord Injury (SCI) is a significant neurological disorder that can result in severe motor and cognitive impairments. Neuronal regeneration and functional recovery are critical aspects of SCI treatment, with calcium signaling being a crucial indicator of neuronal excitability. In this study, we utilized a murine model to investigate the effects of targeted wireless electrical stimulation (ES) on neuronal activity following SCI. After establishing a complete SCI model in normal mice, flexible electrodes were implanted, and targeted wireless ES was administered to the injury site. We employed fiber-optic photometric in vivo calcium imaging to monitor calcium signals in pyramidal neurons within the CA3 region of the hippocampus and the M1 region of the primary motor cortex. The experimental results demonstrated a significant reduction in calcium signals in CA3 and M1 pyramidal neurons following SCI (reduced by 76 % and 59 %, in peak respectively). However, the application of targeted wireless ES led to a marked increase in calcium signals in these neurons (increased by 118 % and 69 %, in peak respectively), indicating a recovery of calcium activity. These observations suggest that wireless ES has a positive modulatory effect on the excitability of pyramidal neurons post-SCI. Understanding these mechanisms is crucial for developing therapeutic strategies aimed at enhancing neuronal recovery and functional restoration following spinal cord injuries., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

RNA modification has recently become a significant process of gene regulation, and the methyltransferase-like (METTL) family of proteins plays a critical role in RNA modification, methylating various types of RNAs, including mRNA, tRNA, microRNA, rRNA, and mitochondrial RNAs. METTL proteins consist of a unique seven-beta-strand domain, which binds to the methyl donor SAM to catalyze methyl transfer. The most typical family member METTL3/METTL14 forms a methyltransferase complex involved in N6-methyladenosine (m6A) modification of RNA, regulating tumor proliferation, metastasis and invasion, immunotherapy resistance, and metabolic reprogramming of tumor cells. METTL1, METTL4, METTL5, and METTL16 have also been recently identified to have some regulatory ability in tumorigenesis, and the rest of the METTL family members rely on their methyltransferase activity for methylation of different nucleotides, proteins, and small molecules, which regulate translation and affect processes such as cell differentiation and development. Herein, we summarize the literature on METTLs in the last three years to elucidate their roles in human cancers and provide a theoretical basis for their future use as potential therapeutic targets., (© 2023. The Author(s).)

Virus spillover remains a major challenge to public health. A panel of SARS-CoV-2-related coronaviruses have been identified in pangolins, while the infectivity and pathogenicity of these pangolin-origin coronaviruses (pCoV) in humans remain largely unknown. Herein, we comprehensively characterized the infectivity and pathogenicity of a recent pCoV isolate (pCoV-GD01) in human cells and human tracheal epithelium organoids and established animal models in comparison with SARS-CoV-2. pCoV-GD01 showed similar infectivity to SARS-CoV-2 in human cells and organoids. Remarkably, intranasal inoculation of pCoV-GD01 caused severe lung pathological damage in hACE2 mice and could transmit among cocaged hamsters. Interestingly, in vitro neutralization assays and animal heterologous challenge experiments demonstrated that preexisting immunity induced by SARS-CoV-2 infection or vaccination was sufficient to provide at least partial cross-protection against pCoV-GD01 challenge. Our results provide direct evidence supporting pCoV-GD01 as a potential human pathogen and highlight the potential spillover risk., (© 2023. The Author(s).)

The first vinylogous dearomatization is reported. Under a photoinduced platform, various benzothiophenes functionalized by ketones at the 3-position could react with 3-methylenechroman-4-ones efficiently, leading to a variety of valuable products that contain the pharmaceutically significant chromones and 2,3-dihydrobenzo[ b ]thiophenes concurrently. The transformations were revealed to experience hydrogen-atom transfer, dearomatization, olefin migration, and radical cross coupling.

Background: Primary gastric linitis plastica (GLP) is a distinct phenotype of gastric cancer with poor survival. Comprehensive molecular profiles and putative therapeutic targets of GLP remain undetermined., Methods: We subjected 10 tumor-normal tissue pairs to whole exome sequencing (WES) and whole transcriptome sequencing (WTS). 10 tumor samples were all GLP which involves 100% of the gastric wall macroscopically. TCGA data were compared to generate the top mutated genes and the overexpressed genes in GLP., Results: Our results reveal that GLP has distinctive genomic and transcriptomic features, dysfunction in the Hippo pathway is likely to be a key step during GLP development. 6 genes were identified as significantly highly mutated genes in GLP, including AOX1, ANKRD36C, CPXM1, PTPN14, RPAP1, and DCDC1). MUC6, as a previously identified gastric cancer driver gene, has a high mutation rate (20%) in GLP. 20% of patients in our GLP cohort had CDH1 mutations, while none had RHOA mutations. GLP exhibits high immunodeficiency and low AMPK pathway activity. Our WTS results showed that 3 PI3K-AKT pathway-related genes (PIK3R2, AKT3, and IGF1) were significantly up-regulated in GLP. Two genes were identified using immunohistochemistry (IHC), IGF2BP3 and MUC16, which specifically expressed in diffuse-type-related gastric cancer cell lines, and its knockdown inhibits PI3K-AKT pathway activity., Conclusions: We provide the first integrative genomic and transcriptomic profiles of GLP, which may facilitate its diagnosis, prognosis, and treatment., (© 2022. The Author(s).)

Background: Zika virus (ZIKV) is an emerging arbovirus of the genus flavivirus that is associated with congenital Zika syndrome (CZS) in newborns. A wide range of clinical symptoms including intellectual disability, speech delay, coordination or movement problems, and hearing and vision loss, have been well documented in children with CZS. However, whether ZIKV can invade the olfactory system and lead to post-viral olfactory dysfunction (PVOD) remains unknown., Methods: We investigated the susceptibility and biological responses of the olfactory system to ZIKV infection using mouse models and human olfactory organoids derived from patient olfactory mucosa., Findings: We demonstrate that neonatal mice infected with ZIKV suffer from transient olfactory dysfunction when they reach to puberty. Moreover, ZIKV mainly targets olfactory ensheathing cells (OECs) and exhibits broad cellular tropism colocalizing with small populations of mature/immature olfactory sensory neurons (mOSNs/iOSNs), sustentacular cells and horizontal basal cells in the olfactory mucosa (OM) of immunodeficient AG6 mice. ZIKV infection induces strong antiviral immune responses in both the olfactory mucosa and olfactory bulb tissues, resulting in the upregulation of proinflammatory cytokines/chemokines and genes related to the antiviral response. Histopathology and transcriptomic analysis showed typical tissue damage in the olfactory system. Finally, by using an air-liquid culture system, we showed that ZIKV mainly targets sustentacular cells and OECs and support robust ZIKV replication., Interpretation: Our results demonstrate that olfactory system represents as significant target for ZIKV infection, and that PVOD may be neglected in CZS patients., Funding: Stated in the acknowledgment., Competing Interests: Declaration of interests The authors declare that they have no conflict of interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Over the recent decades, global plastic production has grown dramatically due to the huge demands of consumption. As a consequence, large amounts of plastic waste have accumulated in the environment and will be cleaved into microplastics. Due to the low bioavailability, the microplastics will exist in the environment persistently and cause massive environmental stress. Plastic pollution is currently one of the biggest environmental concerns. Recent studies have shown the possibility to obtain degrading microorganisms of microplastics from the natural environment. Some microorganisms can break down microplastics into water and carbon dioxide. This paper reviewed the current research on biodegradation of polyethylene (PE), which is the most abundant microplastic type in the environment, and discussed the quantification methods of the degradation effect. Given that current biodegradation efficiency is relatively limited, further research is required.

Objectives: Subject to ethical constraints, real-world data are an important resource for evaluating treatment effects of medication use during pregnancy and the postpartum period. This study investigated whether motherwort injection, a traditional Chinese medicine preparation, was more effective than intramuscular (IM) oxytocin for preventing postpartum hemorrhage (PPH) in a real-world setting when intravenous (IV) oxytocin is administered. Methods: We conducted an active-controlled, propensity-score matched cohort study using an established pregnancy registry database. Women who underwent cesarean section and received IV oxytocin at the third stage of labor were included. We used an active-comparator design to minimize indication bias, in which we compared IM motherwort injection in the uterus versus IM oxytocin, both on top of IV oxytocin use. We applied 1:1 propensity-score matching (PSM) to balance patient baseline characteristics and used a logistic regression model to estimate treatment effect (i.e., risk difference (RD) and odds ratio (OR)) by using the counterfactual framework. The outcomes of interest were blood loss over 500 ml within 2 h after delivery (PPH, primary) and blood loss over 1,000 ml (severe PPH, secondary). We conducted four sensitivity analyses to examine the robustness of the results. Results: A total of 22,519 pregnant women underwent cesarean sections, among which 4,081 (18.12%) PPH and 480 (2.13%) severe PPH occurred. Among included women, 586 (2.60%) were administrated with IM motherwort injection, and 21,933 (97.40%) used IM oxytocin. After PSM, patient baseline characteristics were well balanced. Compared with IM oxytocin, the use of IM motherwort injection was associated with significantly lower risk of PPH (RD -25.26%, 95% CI -30.04% to -20.47%, p < 0.001; OR 0.25, 95% CI 0.18 to 0.32, p < 0.001) and severe PPH (RD -3.58%, 95% CI -5.87% to -1.30%, p < 0.001; OR 0.39, 95% CI 0.20 to 0.71, p < 0.002). Sensitivity analyses showed that the results were similar. Conclusion: With the use of data from a real-world setting, the findings consistently showed that among women undergoing cesarean section who had received IV oxytocin, the additional use of IM motherwort injection could achieve a lower risk of PPH as compared to the additional use of IM oxytocin. Our study suggested a paradigm for investigating the treatment effect of Chinese herbal medicine in the real-world practice setting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewers JW and YF declared a shared affiliation, with no collaboration, with one of the authors HS to the handling editor at the time of the review., (Copyright © 2022 Li, Liu, Chen, Shang, Wang, Luo, Li, Qi, Xiong, Huang, Wang, Zou, Liu, Tan and Sun.)

Objectives: To evaluate the effectiveness of cervical pessary in preventing preterm birth (PTB) and improving perinatal outcomes among singleton and twin pregnancies., Methods: Electronic databases were systematically searched from their inception until 14 March 2019. Randomized clinical trials comparing the effectiveness of cervical pessary placement with expectant management were included. The primary outcome was the incidence of PTB <34 weeks., Results: Thirteen studies were included, involving eight studies about singleton and six studies about twin pregnancies. For singleton pregnancies with short cervical length, cervical pessary, comparing with expectant treatment, seemed have no effectiveness in preventing PTB <34 weeks (relative risk, 95% confidence interval, 0.73, 0.42-1.28), <37 weeks (0.69, 0.43-1.09), and <28 weeks (0.79, 0.42-1.48); while for twin pregnancies with short cervical length, cervical pessary also did not reduce the risk of PTB <34 weeks (0.81, 0.49-1.35), <37 weeks (0.93, 0.83-1.05), and <28 weeks (0.72, 0.38-1.38). However, cervical pessary seemed have the effectiveness of reducing the risk of spontaneous PTB <28 weeks (0.50, 0.25-0.99) and low birth weight (<1500 g) (0.68, 0.50-0.94) among twin pregnancies with short cervical length. In addition, cervical pessary increased the rate of vaginal discharge and did not improve perinatal outcomes among both singleton and twin pregnancies., Conclusions: Comparing with the expectant treatment, the effectiveness of cervical pessary for reducing the risk of PTB remains uncertain. Additional trials are warranted to further evaluate the effectiveness of cervical pessary.

Objective: To observe the change of cervical curvature and range of motion (ROM) on imaging at 6 months after Hybrid surgery., Methods: A total of 29 patients with cervical degenerative disease who underwent Hybrid surgery from January 2017 to July 2018 were retrospectively analyzed. Also, they all met the inclusion criteria and had complete preoperative and 6 months postoperative imaging data. There were 11 males and 18 females, aged from 34 to 76 (55.86±10.69) years, and the operation time was from 2 to 4(3.03±0.51) hours. The Cobb angle method was used to measure the changes of cervical curvature and ROM of C 2 -C 7 , replacement segments, fusion segments, and upper adjacent segments on cervical lateral X-rays before and 6 months after surgery., Results: There was no statistically significant difference in C 2 -C 7 curvature and ROM between 6 months after operation and before operation ( P >0.05). The degree of curvature and ROM of the replacement segment increased compared with that before operation ( P <0.05). The curvatureof the fusion segment was increased than that before operation ( P <0.05). There was no statistically significant difference in ROM of the fusion segment compared with that before operation ( P >0.05). There was no statistically significant difference in the curvature and ROM of the upper adjacent segments compared with those before operation ( P >0.05). There was no significant difference in the curvature between the replacement and fusion segments before and 6 months after operation ( P >0.05);the ROM of the replacement segment was higher than that of the fusion segment at 6 months after operation ( P <0.05)., Conclusion: Hybrid surgery reconstructs the lordotic curvature of the entire cervical spine and the responsible segment, retains the ROM of the cervical replacement segment, and restores the biomechanical function of cervical spine.

Objective: To investigate the clinical effect of anterior cervical Hybrid surgery in the treatment of cervical degenerative diseases (CDD) and observe the incidence of heterotopic ossification of disc replacement segment at 1 year after surgery., Methods: From January 2015 to April 2018, 35 patients who received anterior cervical hybrid surgery met the inclusion and exclusion criteria and the complete clinical follow up data were analyzed retrospectively. Complete imaging follow-up data were obtained from 24 patients. There were 15 males and 20 females, aged from 39 to 70(55.57±7.73) years old. The amount of bleeding was for 20 to 100 (40.29±18.39) ml, and the hospitalstay was for 4 to 28(11.03±4.63) days, and the follow-up time was(12.97±1.36) months. Clinical outcomes were assessed by the Tanaka Yasushi cervical spondylitis symptom scale 20 score (YT20), and Japanese Orthopaedic Association (JOA) score. The occurrence of heterotopic ossification after Hybrid surgery was evaluated by X-ray according to McAfee standard one year after operation. Patients with or without heterotopic ossificationwere divided into two groups and their clinical effects were compared., Results: At the final follow up, the mean YT20 score and JOA score were significantly higher than those before operation (P <0.05), and the average improvement rate of JOA was (70.66 ±0.44)%. One year after operation, the heterotopic ossification occurred in 10 of 24 segments, with incidence of 41.70%(10/24), including 29.20% in gradeⅠand 12.50% in gradeⅡ. The results of clinical efficacy comparison between patients with and without heterotopic ossification were as follows:there was no significant difference in JOA score before and after operation ( P >0.05);there was no significant difference in YT20 score before operation ( P >0.05), and YT20 score in patients with heterotopic ossification was significantly lower than that in patients without heterotopic ossification( P <0.05)., Conclusion: The short-term clinical effect of Hybrid surgery is satisfactory for cervical degenerative diseases, and the cause of heterotopic ossification still needs tobe further explored.

Objective: To investigate the effect of bone marrow mononuclear cell transplantation on the expression of miRNA-21 and miRNA-155 in mice with ulcerative colitis(UC). Methods: Healthy and clean KM mice aged 6-8 weeks were randomly divided into transplantation group, model group and normal control group with 15 mice in each group. In the transplantation group and model group, dextran sodium sulfate (DSS) was used to establish the model for 24 h. The mice in the transplantation group were injected with 0.4 ml of 4 ', 6-diaminol-2-phenylindole (DAPI) -labeled P3-BM-MNCs cell suspension (3.2×10(6) cells/ml), and the mice in the model group and the normal control group were injected with 0.4 ml phosphate buffer (PBS).UC disease activity index (DAI) was used to test the general condition of mice; HE staining was used to observe the pathological changes of colon tissue; Real-time quantitative PCR was used to detect the expression of miRNA-21 and miRNA-155 mRNA. Results: DAI scores of normal control group, model group and transplantation group were 0 (0,1), 3.1 (2.8,3.3) and 2.7 (2.4,3.1),respectively. Compared with normal control group, the DAI score of model group and transplantation group was higher ( P< 0.05), and the DAI score of transplantation group was lower than that of model group ( P< 0.05). The gross scores of tissue injury in normal control group, model group and transplantation group were 0 (0, 1), 3 (3, 4) and 1 (1, 2), respectively,and the pathological scores of tissue injury were 0 (0, 1), 16 (12, 16) and 6 (6, 8), respectively,compared with the normal control group. The tissue injury score of the model group and the transplantation group was higher ( P< 0.05), and the tissue injury score of the transplantation group was lower than that of the model group ( P< 0.05). The expression levels of miRNA-21 mRNA in normal control group, model group and transplantation group were 0.87±0.15, 2.38±0.29 and 1.59±0.32, respectively, and the expression levels of miRNA-155 mRNA were 1.87±0.46, 7.38±1.97 and 3.92±0.84, respectively, compared with the normal control group, the expression of miRNA-21 and miRNA-155 mRNA in the model group and transplantation group was higher ( P< 0.01), the expression of miRNA-21 and miRNA-155 mRNA in the transplantation group was lower than that of the model group ( P< 0.05). Conclusion: Bone marrow mononuclear cell transplantation can improve the histopathological and DAI scores of mice with UC, which may be related to the down-regulation of miRNA-21 and miRNA-155 mRNA expression.

Background: Liver organoids have recently been applied as models for liver disease and drug screening, especially when combined with liver-on-a-chip technologies. Compared to hepatocyte-like cells, primary hepatocytes have high functionality but cannot maintain their function when cultured in vitro . Mesenchymal stem cells (MSCs) enhance hepatocyte function and maintain hepatocyte metabolism when co-cultured with hepatocytes. MSCs can help induced pluripotent stem cells to generate an organoid structure  via the MSC-based traction force triggered by extracellular matrix (ECM) proteins. In this study, primary hepatocytes were co-cultured with MSCs on a liver-derived ECM to generate liver organoids within a short duration., Aim: To create hepatocyte organoids by co-culturing primary hepatocytes with MSCs on a porcine liver extracellular matrix (PLECM) gel., Methods: Perfusion and enzymatic hydrolysis were used to form the PLECM gel. Rat hepatocytes and human MSCs were mixed and plated on pre-solidified PLECM gel in a 48-well plate for 48 h to generate organoids. Generated organoids were evaluated through hematoxylin and eosin, periodic acid-Schiff, immuno-histological, and immunofluorescence staining, and quantitative PCR for alb , CYP450 gene markers, and urea cycle genes. Culture medium was collected to detect albumin (ALB) and urea production on days 2, 4, 6, 8, 14, and 20., Results: The whole porcine liver was perfused and enzymatically hydrolyzed to form a PLECM gel. The structural components and basement membrane composition of the ECM, such as collagen type I, collagen type IV, fibronectin, and laminin, were demonstrated to be retained. Through interaction of human MSCs with the liver-derived ECM, primary hepatocytes and human MSCs assembled together into a 3D construction and generated primary hepatocyte organoids for 48 h. The mRNAs of the gene alb , the CYP450 gene markers cyp1a1, cyp1a2 , and cyp3a2 as well as urea cycle genes arg-1, asl, ass-1, cps-1, nags were highly expressed in hepatocyte organoids. Long-term survival of the primary hepatocyte organoids, as well as stable functionality, was demonstrated via ALB and urea production in vitro ., Conclusion: Our new method of creating primary hepatocyte organoids by co-culturing hepatocytes with MSCs on liver-derived ECM hydrogels could be used to develop models for liver disease and for drug screening., Competing Interests: Conflict-of-interest statement: All the authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objective: To study the association between prepregnancy subnormal body weight and obstetrical outcomes after autologous in vitro fertilization (IVF) cycles., Design: Systematic review and meta-analysis., Setting: Not applicable., Patient(s): Women with prepregnancy subnormal body weight (body mass index <18.5 kg/m 2 ) and normal body weight (body mass index 18.5-25 kg/m 2 ) after assisted reproductive treatment., Interventions(s): None., Main Outcome Measure(s): Clinical pregnancy rate (CPR), live birth rate (LBR), and miscarriage rate. CPR and LBR were calculated at per-woman and per-cycle levels., Result(s): A total of 38 cohort studies with low risk of bias were included. Meta-analyses showed that, compared with normal-weight women, those underweight before pregnancy had a lower CPR at per-woman and per-cycle levels. Compared with normal weight, underweight before pregnancy had little impact on LBR at both per-woman and per-cycle levels, nor on miscarriage rate., Conclusion(s): Compared with women of normal weight, women who were underweight before pregnancy had modest association with a lower CPR, but underweight did not seem to affect LBR or miscarriage after IVF., (Copyright © 2019 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Previous meta-analyses assessing anesthetic techniques in adult patients undergoing hip fractures surgery are available. However, whether the anesthetic technique is associated with risk of mortality and complications in geriatric patients with hip fractures remains unclear. This study was conducted to assess postoperative outcomes of anesthesia technique in geriatric patients undergoing hip fracture surgery., Methods: Cochrane Library, PubMed, EMBASE, MEDLINE, CNKI, and CBM were searched from inception up to May 25, 2018. Observational studies and randomized controlled trials (RCTs) that assessed the perioperative outcomes of technique of anesthesia (general or regional [epidural/spinal/neuraxial]) in geriatric patients (≥60 years old) undergoing hip fracture surgery were included. Two investigators independently screened studies for inclusion and performed data extraction. Heterogeneity was assessed by the I and Chi-square tests. The odds ratio (OR) of the dichotomous data, mean difference (MD) of continuous data, and 95% confidence intervals (CI) were calculated to assess the pooled data., Results: Eleven retrospective and 2 RCTs were included. There was no difference in 30-day mortality (OR = 0.96; 95% CI 0.86-1.08; P = .51) between the general and regional anesthesia groups. In-hospital mortality (OR = 1.26; 95% CI 1.17-1.36; P < .001), acute respiratory failure (OR = 2.66; 95% CI 2.34-3.02; P < .001), length of hospital stay (MD = 0.33; 95% CI 0.24-0.42; P < .001), and readmission (OR = 1.09; 95% CI 1.01-1.18; P = .03) were significantly reduced in the regional anesthesia group. Pneumonia (OR = 0.99; 95% CI 0.91-1.07; P = .79), heart failure (OR = 0.97; 95% CI 0.86-1.09; P = .62), acute myocardial infraction (OR = 1.07; 95% CI 0.99-1.16; P = .10), acute renal failure (OR = 1.32; 95% CI 0.97-1.79; P = .07), cerebrovascular accident (OR = 1.08; 95% CI 0.82-1.42; P = .58), postoperative delirium (OR = 1.51; 95% CI 0.16-13.97; P = .72), and deep vein thrombosis/pulmonary embolism (OR = 1.42; 95% CI 0.84-2.38; P = .19) were similar between the two anesthetic techniques., Conclusion: General anesthesia is associated with increased risk of in-hospital mortality, acute respiratory failure, longer hospital stays, and higher readmission. There is evidence to suggest that regional anesthesia is associated with improved perioperative outcomes. Large RCTs are needed to explore the most optimal anesthetic techniques for geriatric patients with hip fractures before drawing final conclusions., Prospero Registration Number: CRD42018093582.

Background: Acute liver failure (ALF) has a high mortality varying from 80% to 85% with rapid progress in multi-organ system failure. Bioartificial liver (BAL) support systems have the potential to provide temporary support to bridge patients with ALF to liver transplantation or spontaneous recovery. In the past decades, several BAL support systems have been conducted in clinical trials. More recently, concerns have been raised on the renovation of high-quality cell sources and configuration of BAL support systems to provide more benefits to ALF models in preclinical experiments., Aim: To investigate the characteristics of studies about BAL support systems for ALF, and to evaluate their effects on mortality., Methods: Eligible clinical trials and preclinical experiments on large animals were identified on Cochrane Library, PubMed, and EMbase up to March 6, 2019. Two reviewers independently extracted the necessary information, including key BAL indicators, survival and indicating outcomes, and adverse events during treatment. Descriptive analysis was used to identify the characteristics of the included studies, and a meta-analysis including only randomized controlled trial (RCT) studies was done to calculate the overall effect of BAL on mortality among humans and large animals, respectively., Results: Of the 30 selected studies, 18 were clinical trials and 12 were preclinical experiments. The meta-analysis result suggested that BAL might reduce mortality in ALF in large animals, probably due to the recent improvement of BAL, including the type, cell source, cell mass, and bioreactor, but seemed ineffective for humans [BAL vs control: relative risk (95% confidence interval), 0.27 (0.12-0.62) for animals and 0.72 (0.48-1.08) for humans]. Liver and renal functions, hematologic and coagulative parameters, encephalopathy index, and neurological indicators seemed to improve after BAL, with neither meaningful adverse events nor porcine endogenous retrovirus infection., Conclusion: BAL may reduce the mortality of ALF by bridging the gap between preclinical experiments and clinical trials. Clinical trials using improved BAL must be designed scientifically and conducted in the future to provide evidence for transformation., Competing Interests: Conflict-of-interest statement: The authors have no conflict of interests to disclose.

Objective: To investigate whether the association between in vitro fertilisation (IVF) and severe maternal morbidity (SMM) was mediated by multiple gestations., Design: A retrospective cohort study., Setting: The study was conducted at six hospitals in China., Participants: Pregnant women at 20 gestational weeks or longer., Outcome Measure: The outcome was SMM, which was a composite of potential life-threatening conditions, the use of critical medical interventions, or the status of maternal near-miss that occurred during pregnancy, childbirth or within 42 days of pregnancy termination, as defined by WHO., Results: In total, 22 368 eligible pregnant women were included, among whom 497 (2.2%) received IVF, and 776 developed SMM (incidence 34.7/1000 live births, 95% CI 32.3/1000 to 37.1/1000). Four multivariable logistic regression models were constructed. Model 1, without including the variable of multiple gestations, showed that IVF was associated with higher risk of SMM (adjusted OR (aOR) 1.54, 95% CI 1.03 to 2.29). Model 2, assessing the association between IVF and multiple gestations, showed that IVF was strongly associated with multiple gestations (aOR 14.75, 95% CI 11.38 to 19.10). Model 3, by adding the variable of multiple gestations to model 1, showed that IVF was not statistically associated with SMM (aOR 0.89, 95% CI 0.58 to 1.36), but multiple gestations were associated with higher risk of SMM (aOR 5.92, 95% CI 4.88 to 7.83). Model 4, investigating the association between IVF and SMM among singleton pregnancies, showed no statistically significant association (aOR 0.70, 95% CI 0.37 to 1.32). An additional analysis by adding the interaction term of IVF by multiple gestations to model 3 showed no statistical significance of the interaction term (aOR 1.15, 95% CI 0.36 to 3.68), confirming the absence of exposure-mediator interaction., Conclusions: Using the established rule for judging mediation effect, the results suggested that multiple gestations might mediate the association between the use of IVF and higher risk of SMM. Further prospective studies are warranted to test our finding., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Polymer materials exhibit unique properties in the fabrication of optical waveguide devices, electromagnetic devices, and bio-devices. Direct laser writing (DLW) technology is widely used for micro-structure fabrication due to its high processing precision, low cost, and no need for mask exposure. This paper reviews the latest research progresses of polymer-based micro/nano-devices fabricated using the DLW technique as well as their applications. In order to realize various device structures and functions, different manufacture parameters of DLW systems are adopted, which are also investigated in this work. The flexible use of the DLW process in various polymer-based microstructures, including optical, electronic, magnetic, and biomedical devices are reviewed together with their applications. In addition, polymer materials which are developed with unique properties for the use of DLW technology are also discussed.

Objective: To investigate the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in pregnant women in urban areas of China. Methods: The study was a national cross-sectional survey conducted from September 19th, 2016 to November 20th, 2016. According to the classification of the National Bureau of Statistics, all survey sites were set up in 6 regions of the country.Pregnant women were continuously selected using multistage stratified sampling. A total of 12 403 pregnant women were collected and examined for serum ferritin and hemoglobin levels. Results: The median serum ferritin level during pregnancy was 20.60 μg/L (11.78-36.98 μg/L) , the hemoglobin level was (118±12) g/L. With the progress of pregnancy, the levels of serum ferritin and hemoglobin decreased gradually. The median serum ferritin levels in the first, second trimester and third trimester were 54.30 μg/L (34.48-94.01 μg/L) , 28.60 μg/L (16.40-50.52 μg/L) , and 16.70 μg/L (10.20-27.00 μg/L) respectively ( P< 0.01) . The mean hemoglobin levels were (127±10) g/L, (119±11) g/L and (117±11) g/L respectively ( P< 0.01) . The prevalence of ID in urban pregnant women was 48.16% (5 973/12 403) , and IDA prevalence was 13.87% (1 720/12 403) . The prevalence of IDA in the first, second trimester and third trimester were 1.96% (20/1 019) , 8.40% (293/3 487) and 17.82% (1 407/7 897) ,respectively ( P< 0.01) . The prevalence of standardized ID and IDA were significantly different in various regions of China ( P< 0.01) . The standardized prevalence of ID were relatively higher in East China and Northeast China, 57.37% and 53.41% respectively, while it was the lowest in Southwest China, 30.51%. The standardized prevalence of IDA in South Central, Northwest, and East China were relatively high, 21.30%, 16.97% and 17.53% respectively, and the standardized prevalence of IDA in Southwest China was the lowest, 5.44%, the differents in various regions were significant (all P< 0.01) . Conclusion: The current phenomenon of ID and IDA in pregnant women is still very common, and nutrition and health care during pregnancy should be strengthened.

Background: The effect of maternal weights on the risk of iron deficiency anemia (IDA) during pregnancy remains unclear. The study aimed to investigate the association between maternal weight indicators and IDA during pregnancy., Methods: We conducted a cohort study to examine the association between maternal weight indicators, including prepregnancy body mass index and the rate of gestational weight gain (GWG), and the risk of IDA among Chinese pregnant women. Data about new-onset IDA at different trimesters from a national cross-sectional survey were collected; information regarding baseline variables and rate of GWG from women participating in the survey were retrospectively collected. Tested IDA and reported IDA were documented. Multilevel logistic regression to examine the association between maternal weight indicators and the risk of IDA after adjusting for potential confounders was conducted., Results: This study enrolled 11,782 pregnant women from 24 hospitals from September 19, 2016, to November 20, 2016. Among those, 1515 (12.9%) IDA events were diagnosed through test (test IDA); 3915 (33.3%) were identified through test and patient reporting (composite IDA). After adjusting for confounders and cluster effect of hospitals, underweight pregnant women, compared with normal women, were associated with higher risk of test IDA (adjusted odds ratio [aOR]: 1.35, 95% confidence interval [CI]: 1.17-1.57 and composite IDA (aOR: 1.35, 95% CI: 1.21-1.51); on the contrary, overweight and obese women had lower risk of test IDA (aOR: 0.68, 95% CI: 0.54-0.86 overweight; aOR: 0.30, 95% CI: 0.13-0.69 obese) and composite IDA (aOR: 0.77, 95% CI: 0.67-0.90 overweight; aOR: 0.34, 95% CI: 0.21-0.55 obese). The higher rate of GWG was associated with higher risk of IDA (test aOR: 1.86 95% CI: 1.26-2.76; composite aOR: 1.54, 95% CI: 1.16-2.03)., Conclusions: Pregnant women who are underweight before pregnancy and who have faster GWG are more likely to develop IDA. Enforced weight control during pregnancy and use of iron supplements, particularly among underweight women, may be warranted., Competing Interests: There are no conflicts of interest

Objective: To investigate the correlation of seminal plasma homocysteine (Hcy) and its metabolic factors folate (FA) and cobalamin (VB12) with semen quality in obese men., Methods: We randomly selected 83 male patients with idiopathic infertility for this study and, according to the body mass index (BMI), divided them into a normal BMI (n = 28), an overweight (n = 28) and an obesity group (n = 27). We determined the levels of Hcy, FA and VB12 in the seminal plasma by ELISA and analyzed their correlation with the semen parameters of the patients in different groups., Results: Compared with the normal BMI group, the obese males showed significant decreases in the semen volume (［3.23 ± 0.86］ vs ［2.58 ± 0.77］ ml, P < 0.05), total sperm count (［191.35 ± 103.00］ vs ［121.55 ± 88.08］ ×106, P < 0.05), percentage of progressively motile sperm (［52.88 ± 15.58］ % vs ［38.97 ± 16.52］ %, P < 0.05), seminal plasma Hcy (［7.41 ± 1.29］ vs ［6.62 ± 0.85］ μmol/L, P < 0.05), and VB12 (［282.41 ± 30.38］ vs ［230.07 ± 37.75］ pmol/L, P < 0.05). There were no statistically significant differences in the semen parameters between the overweight group and the normal BMI or the obese group (P > 0.05), or in sperm concentration or the FA level among the three groups of patients (P > 0.05). The levels of seminal plasma Hcy and VB12 were correlated positively with the semen volume (r = 0.281 and 0.242, P < 0.05) and total sperm count (r = 0.229 and 0.258, P < 0.05) but negatively with BMI (r = －0.293 and －0.238, P < 0.05). No correlation, however, was found either between sperm concentration and the percentage of progressively motile sperm (P > 0.05) or between the FA level and BMI or semen parameters (P > 0.05)., Conclusions: The levels of seminal plasma Hcy and VB12 are correlated with BMI, semen volume and total sperm count, which suggests that the concentrations of seminal plasma Hcy and VB12 may be associated with the fertility of obese men.

Objective: To investigate the influence of insulin resistance on male reproductive hormones and semen quality., Methods: Using the electrochemiluminescence method, we measured the levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), estradiol (E2) and testosterone (T) in the serum of 83 infertile males. We detected the levels of fasting plasma glucose (FPG) and fasting insulin (FINS) and calculated the insulin resistance index presented as homeostasis model assessment of insulin resistance (HOMA-IR). Based on HOMA-IR, we divided the patients into three tertile groups, T1 (HOMA-IR 0.36－0.55, n = 27), T2 (HOMA-IR 0.56－0.80, n = 28) and T3 (HOMA-IR 0.81－1.97, n = 28), obtained their semen parameters by computer-assisted semen analysis (CASA) and analyzed the correlation of HOMA-IR with male reproductive hormone levels and semen parameters., Results: With the elevation of HOMA-IR, the patients of the T1, T2 and T3 groups showed significant decreases in the serum T level (［14,26 ± 4.27］ vs ［14.75 ± 5.00］ vs ［11.62 ± 3.68］ nmol/L, P <0.05) and the percentage of progressively motile sperm (PMS) (［51.04 ± 15.10］% vs ［48.04 ± 16.24］% vs ［37.84 ± 18.23］%, P <0.05). HOMA-IR was correlated negatively with the serum T level (r = －0.333, P = 0.002), semen volume (r = －0.23, P = 0.029) and PMS (r = －0.27, P = 0.015), and so was FINS with the serum T level (r = －0.327, P = 0.003) and PMS (r = －0.315, P = 0.004), while the semen volume was correlated positively with the levels of serum T (r = 0.221, P = 0.048) and FSH (r = 0.222, P = 0.047). Multivariate linear regression analysis showed that HOMA-IR was an independent influencing factor for PMS and the body mass index (BMI) was that for the semen volume and total sperm count., Conclusions: Insulin resistance may reduce semen quality by changing the levels of male reproductive hormones.

Decompression is the major therapeutic strategy for acute spinal cord injury, but there is some debate about the time window for decompression following spinal cord injury. An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury. Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord. In this study, Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury. The rat models were established by inserting a balloon catheter into the atlanto-occipital space. The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression. Electroacupuncture was conducted at the acupoints Dazhui (GV14) and Baihui (GV 20) (2 Hz, 15 minutes) once a day for 14 consecutive days. Compared with decompression alone, hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture. However, the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours. Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone. These findings indicate that compared with decompression alone, Governor Vessel electroacupuncture combined with delayed decompression (48 hours) is more effective in the treatment of upper cervical spinal cord injury. Governor Vessel electroacupuncture combined with early decompression (12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury. Nevertheless, further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone., Competing Interests: The authors have no conflicts of interest to declare

Objective: To investigate the relationship between seminal plasma zinc alpha-2 glycoprotein (ZAG) and semen quality in obese males., Methods: This study included 130 obese male patients with idiopathic infertility Based on the concentration of seminal plasma ZAG, we divided the patients into three tertile groups: tertile 1 (T1, 73.45－97.15 μg/ml, n = 43), T2 (97.16－115.46 μg/ml, n = 44), and T3 (115.47－220.11 μg/ml, n = 43). We measured the concentrations of seminal plasma zinc (SPZ) and ZAG of the patients by ELISA, obtained the semen parameters, and analyzed the correlation of semen quality with the levels of SPZ and ZAG and the influence of obesity on SPZ, ZAG and semen quality., Results: The mean level of seminal plasma ZAG in the 130 obese male patients was (111.29 ± 26.50) μg/ml. There were statistically significant differences in sperm concentration and total sperm count among the three tertile groups (P < 0.05). The level of seminal plasma ZAG was correlated negatively with the body mass index (BMI), waist circumference (WC), sperm concentration and sperm count (P < 0.01), that of SPZ positively with BMI and WC (P < 0.05) but negatively with semen volume and the percentage of progressively motile sperm (P < 0.05). The level of serum ZAG, however, exhibited no correlation with SPZ, seminal plasma ZAG or semen quality. Obesity was found to be associated with significantly decreased concentration of seminal plasma ZAG and percentage of progressively motile sperm but remarkably increased level of SPZ (P < 0.05)., Conclusions: Obesity may induce the metabolic disorder of SPZ and ZAG, change the microenvironment of seminal plasma, and consequently affect semen quality.

Objective: To investigate the effect and mechanism of Buyanghuanwu decoction on platelet activating factor expression in spinal cord tissue of model of acute upper cervical spinal cord injury in rats., Methods: Sixty SPF grade 3-month-old female Wistar rats were randomly divided into sham operation group, model group, methylprednisolone group and Buyanghuanwu decoction (Traditional Chinese Medicine group, TCM), with 15 rats in each group. The first day after the modeling, the methylprednisolone group were treated by injection of the tail vein for a total of 24 h, the first dose of 30 mg/kg, followed by a dose of 5.4 mg/kg·h, and 1 time per 4 h. The traditional Chinese medicine group was prepared with a medium dose of Buyanghuanwu decoction granules which were prepared into a solution containing 2 g/ml of granules, 3.5 g/kg per day gavage, was equivalent to 1 time the amount of adult consumption. The model group and the sham operation group were given equal volume of normal saline for 2 times a day for 2 weeks. The recovery of nerve function was evaluated by BBB classification at 1, 3, 7, 14 days after treatment. The expression of PAF in the segment of spinal cord injury was detected by double antibody sandwich (ELISA) method at 1, 7, and 14 d postoperatively., Results: At the first day after treatment, BBB score in model, TCM and methylprednisolone groups were lower than that of sham operation group( P <0.01), but there was no difference among the three groups( P >0.05). At 7, 14 days afer treatment, BBB score in TCM and methylprednisolone groups were higher than that of model group significantly( P <0.01); but there were no significant difference between TCM group and methylprednisolone group( P >0.05). PAF expression in TCM group and methylprednisolone group were lower than that of model group at 7, 14 day afer treatment significantly ( P <0.05); but there were no significant difference between TCM group and methylprednisolone group ( P >0.05)., Conclusions: Buyanghuanwu decoction treatment after acute upper cervical spinal cord injury can significantly improve locomotor recovery by inhibiting the expression of PAF., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To compare the clinical effect between spinal card decompression combined with traditional Chinese medicine and simple spinal card decompression for cervical spondylotic myelopathy., Methods: From June 2012 to June 2015, 73 patients with cervical spondylotic myelopathy were treated, including 42 males and 31 females, aged from 29 to 73 years old with a mean of 50.9 years old. The patients were divided into the simple operation group (34 cases) and the operation combined with traditional Chinese medicine group(39 cases) according to the idea of themselves. The anterior discectomy or subtotal corpectomy with internal fixation or posterior simple open-door decompression with lateral mass screw fixation were performed in the patients. Among them, 39 cases were treated with traditional Chinese medicine after surgery. The Japanese orthopedic association (JOA) score of spinal cord function, the improvement rate of neural function, the neck dysfunction index (NDI) score and the governor vessel stasis syndrome score were compared between two groups preoperative and postoperative 1 week, 1 month and the final follow-up respectively. The internal fixation and the condition of spinal cord decompression were observed by CT, MRI and X-rays before and after operation., Results: All the operations were successful, no injuries such as dura mater, spinal cord and nerve root were found. All the wounds were healed without infection except one patient had a superficial infection. It was solved after intermittent debridement and anti-infective therapy. Hematoma occurred in 1 case, complicated with spinal cord compression, caused incomplete paralysis, and promptly performed the re-operation to remove the hematoma without any obvious sequelae. All the patients were followed up from 12 to 24 months, (14.6±0.8) months for simple operation group and (13.5±0.7) months for operation combined with traditional Chinese medicine group, and there was no significant difference( P >0.05). The scores of JOA, NDI and the governor's vessel stasis syndrome in simple operation group were 8.31±3.15, 29.91±4.52, 6.58±1.31 before operation, and 10.21±2.58, 18.67±4.31, 8.24±1.18 one week after operation, and 11.38±2.85, 16.11±3.18, 8.91±2.11 one month after operation, and 12.21±3.12, 14.61±3.28, 9.12±1.56 at final follow-up, respectively; and in operation combined with traditional Chinese medicine group were 8.29±3.47, 30.83±4.14, 6.38±1.81before operation, and 10.48±2.39, 17.59±5.14, 8.33±1.57 one week after operation, and 12.14±3.12, 13.14±3.21, 9.55±2.49 one month after operation, and 13.85±3.34, 12.11±2.51, 10.33±1.95 at final follow-up, respectively. Postoperative JOA , NDI, and the governor vessel stasis syndrome score of two groups were significantly higher than preoperativee( P <0.05). There was no significant difference in JOA, NDI, and the governor vessel stasis syndrome score between two groups one week after operation ( P >0.05). The above items in operation combined with traditional Chinese medicine group was better than that of simple operation group one month and final follow-up after operation ( P <0.05). The improvement rate of neural function in simple operation group was (67.59±10.78)%, and in operation combined traditional Chinese medicine group was (66.88±12.15)%, there was no significant difference between two groups( P >0.05). There were no complications such as internal fixation failure or re-dislocation of atlas by postoperative CT, MRI and X-rays examination., Conclusions: Spinal card decompression for the treatment of cervical spondylotic myelopathy can extend the spinal canal, relieve the compression of nerve, achieve the deoppilation of governor vessel, the regulation of qi and blood, the restore of Yangqi, combined with traditional Chinese medicine of activating blood removing stasis, warming yang and activating meridians, reinforcing liver benefiting kidney, which may obtain better clinical effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Objective: To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury., Methods: Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method., Results: BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher( P <0.05); and there was no significant difference between group C and group D( P >0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E ( P >0.05), group C was lower than the other groups ( P <0.05); the concentration of tissue PAF, there was no significant difference between group A and group B( P >0.05), group D was significantly higher than that of group A, B, and C( P <0.05), group E was the highest one than that of the other groups( P <0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar ( P >0.05), group C was higher than that of group A and B( P <0.05), group D was higher than group A, B and C( P <0.05), group E was the highest than that of group A, B, C and D ( P <0.05)., Conclusions: Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© 2018 by the China Journal of Orthopaedics and Traumatology Press.)

Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.

Background: Previous studies suggest a combined effect of insulin-like growth factor 1 (igf-1) and igf binding protein 3 (igfbp-3) gene polymorphisms, xenoestrogen, and phytoestrogen on the igf-1 signalling pathway and serum concentrations in the igf system, which are associated with premenopausal breast cancer (bca) risk., Methods: Between 2010 and 2012, our study recruited 140 premenopausal bca patients and 160 community-based premenopausal control subjects. Participants were surveyed about oral contraceptive (oc) use, dietary habits, and other bca risk factors. TaqMan assays were used to determine igf-1 rs1520220 and igfbp-3 rs2854744 genotypes. Daily intakes of energy-adjusted soy isoflavones (easis) were calculated by the residual method. Multivariate logistic regression was applied to estimate the adjusted odds ratios (ors) and 95% confidence intervals (cis) of the igf-1 rs1520220 and igfbp-3 rs2854744 genotypes, oc use, and intake of easis. Stratified analyses were performed to detect the gene-environment combined effect, and multivariate logistic regression was used to estimate interaction coefficients (iors) by the multiplicative model, with 95% cis. The delta method was used to calculate interaction coefficients by the additive model [relative excess risk of interaction (reri), attributable proportions of interaction (apis)] and 95% cis., Results: The igf-1 and igfbp-3 genotypes, oc use, and easis were not found to be associated with bca risk (p > 0.05). Stratified analysis showed that the risk of bca was markedly increased in women carrying the igfbp-3C allele and using ocs compared with women either carrying the igfbp-3C allele or using ocs (or: 3.02; 95% ci: 1.04 to 8.79). The interaction coefficients ior, reri, and api were 4.89 (95% ci: 1.09 to 21.90), 2.42 (95% ci: -0.76 to 5.61), and 0.80 (95% ci: 0.46 to 1.67) respectively., Conclusions: The igfbp-3 rs2854744 polymorphism and oc use might synergistically increase premenopausal bca risk.

An appropriate level of higher alcohols produced by yeast during the fermentation is one of the most important factors influencing Chinese rice wine quality. In this study, BAT1 and BAT2 single- and double-gene-deletion mutant strains were constructed from an industrial yeast strain RY1 to decrease higher alcohols during Chinese rice wine fermentation. The results showed that the BAT2 single-gene-deletion mutant strain produced best improvement in the production of higher alcohols while remaining showed normal growth and fermentation characteristics. Furthermore, a BAT2 single-gene-deletion diploid engineered strain RY1-Δbat2 was constructed and produced low levels of isobutanol and isoamylol (isoamyl alcohol and active amyl alcohol) in simulated fermentation of Chinese rice wine, 92.40 and 303.31 mg/L, respectively, which were 33.00 and 14.20 % lower than those of the parental strain RY1. The differences in fermentation performance between RY1-Δbat2 and RY1 were minor. Therefore, construction of this yeast strain is important in future development in Chinese wine industry and provides insights on generating yeast strains for other fermented alcoholic beverages.

Background: Higher insulin-like growth factor (IGF)-1 and lower IGF binding protein (BP)-3 levels have been associated with higher commoncancer risk, including breast cancer. Dietary factors, genetic polymorphisms, and the combination of both may influence circulating IGF-1 and IGFBP-3 serum concentrations., Methods: From September 2011 to July 2012, we collected demographic, reproductive and dietary data on 143 women (≥ 40 years). We genotyped IGF-1 rs1520220 and IGFBP-3 rs2854744 and measured circulating IGF-1 and IGFBP-3 levels in serum. Covariance analyses were used to estimate the associations of serum levels of IGF-1 and IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3 with IGF-1 rs1520220 and IGFBP-3 rs2854744 genotypes. We subsequently assessed the combined influence of genetics and diet (daily intake of protein, fat and soy isoflavones) on IGF-1 and IGFBP-3 levels., Results: Among women aged less than 50 years, circulating IGF-1 serum levels were significantly lower for those with CC genotype for IGF-1 rs1520220 than levels for those with the GC or GG genotypes (in recessive model: P = 0.007).In gene-diet analyses among these women, we found carrying CC genotype for IGF-1 rs1520220 and high soy isoflavone intake tend to be associated with lower circulating IGF-1 levels synthetically (P = 0.002). Women with GG or GC genotypes for IGF-1 rs1520220 and with low intake of soy isoflavones had the highest levels of circulating IGF-1 (geometric mean [95% CI]: 195 [37, 1021] µg/L). Comparatively, women with both the CC genotype and high soy intake had the lowest levels of circulating IGF-1 (geometric mean [95% CI]: 120 [38,378] µg/L)., Conclusions: IGF-1 serum levels are significantly lower among women with the CC genotype for IGF-1-rs1520220. High soy isoflavone intake may interact with carrying CC genotype for IGF-1-rs1520220 to lower women's serum IGF-1 levels more.

A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed to rapidly detect foot-and-mouth disease virus serotype C (FMDV C). By testing 10-fold serial dilutions of FMDV C samples, sensitivity of the FMDV C RT-LAMP was found to be 10 times higher than that of conventional reverse transcription- PCR (RT-PCR). No cross-reactivity with A, Asia 1, or O FMDV or swine vesicular disease virus (SVDV) indicated that FMDV C RT-LAMP may be an exciting novel method for detecting FMDV C.

Fecal coliform bacteria are used as indicator organisms for the presence of pathogens. In sludges, it has often been assumed that the counts of fecal coliforms after digestion (where the sludges may also be called biosolids) are representative of the counts when the sludge is disposed or recycled, such as by land application. The possibility has been raised, however, that dewatering processes can lead to increased counts of fecal coliforms and, by inference, human pathogens. This paper presents data from previous studies of this possibility; the results were inconsistent but showed observable increases in fecal coliforms at one treatment plant. Additional studies were then performed at another treatment facility, which showed statistically significant increases in fecal coliform counts after dewatering and two days of aging. The increases exceeded two orders of magnitude and included two centrifuge types and two biosolids types. Artifacts of media type and enumeration method have been excluded, and shearing of the material by commercial blender did not produce the same effects.