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Xiaoyao San (XYS) is a classic Chinese medicine prescription. It is traditionally used to relieve syndrome of "liver stagnation and spleen deficiency", a common syndrome type in traditional Chinese medicine, through soothing liver, tonifying spleen, and nourishing blood. Correspondingly, XYS has long application in the treatment of depression, dyspepsia and liver diseases. Given the rising of cutting-edge researches on XYS, there's a significant need to diligently uncover the bioactive constituents and action mechanisms of XYS for treating non-alcoholic fatty liver disease accordingly., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Aims: As a biomarker of insulin resistance (IR) in patients with acute myocardial infarction (AMI), the triglyceride-glucose index (TyG index) has received significant attention. However, most research on AMI has focused on male patients, as it is traditionally believed to primarily affect males. Therefore, this study was conducted on a female population with AMI to investigate the potential correlation between the TyG index and their outcomes., Methods: A total of 320 women who were admitted to Fujian Provincial Hospital for AMI between January 2017 and December 2019 were included in this study. The TyG index was calculated using the following formula: ln [fasting triglycerides (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The primary endpoint of the study was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which included all-cause mortality, myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. The association between the TyG index and unfavorable outcomes in female patients was investigated using the Cox proportional hazards regression model., Results: It was ultimately estimated that 111 patients developed MACCEs. Females with high TyG indices had a higher prevalence of diabetes, elevated heart rates, and hemoglobin A1c, as well as a higher likelihood of undergoing thrombus aspiration and stent placement. The TyG index was found to be positively correlated with the prevalence of hypertension, diabetes, low-density lipoprotein cholesterol, hemoglobin A1c, and damaged vessels. However, this correlation was modest, yet statistically significant. Furthermore, after adjusting for conventional risk factors, the TyG index (HR: 4.292, 95% CI: 2.784-6.616, p  < 0.001) was independently associated with MACCEs., Conclusion: As an independent risk predictor, the TyG index has the potential to enhance clinical outcomes for women with AMI., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Health Science Reports published by Wiley Periodicals LLC.)

As an appendage of the skin, hair protects against ultraviolet radiation and mechanical damage and regulates body temperature. It also reflects an individual's health status and serves as an important method of expressing personality. Hair loss and graying are significant psychosocial burdens for many people. Hair is produced from hair follicles, which are exclusively controlled by the dermal papilla (DP) at their base. The dermal papilla cells (DPCs) comprise a cluster of specialized mesenchymal cells that induce the formation of hair follicles during early embryonic development through interaction with epithelial precursor cells. They continue to regulate the growth cycle, color, size, and type of hair after the hair follicle matures by secreting various factors. DPCs possess stem cell characteristics and can be cultured and expanded in vitro. DPCs express numerous stemness-related factors, enabling them to be reprogrammed into induced pluripotent stem cells (iPSCs) using only two, or even one, Yamanaka factor. DPCs are an important source of skin-derived precursors (SKPs). When combined with epithelial stem cells, they can reconstitute skin and hair follicles, participating in the regeneration of the dermis, including the DP and dermal sheath. When implanted between the epidermis and dermis, DPCs can induce the formation of new hair follicles on hairless skin. Subcutaneous injection of DPCs and their exosomes can promote hair growth. This review summarizes the in vivo functions of the DP; highlights the potential of DPCs in cell therapy, particularly for the treatment of hair loss; and discusses the challenges and recent advances in the field, from basic research to translational applications.

Background: 3% chloroprocaine (CP) has been reported as the common local anesthetic used in pregnant women undergoing urgent cesarean delivery during labor analgesia period. However, 0.75% ropivacaine is considered a promising and effective alternative. Therefore, we conducted a randomized controlled trial to compare the effectiveness and safety of 0.75% ropivacaine with 3% chloroprocaine for extended epidural anesthesia in pregnant women., Methods: We conducted a double-blind, randomized, controlled, single-center study from November 1, 2022, to April 30, 2023. We selected forty-five pregnant women undergoing urgent cesarean delivery during labor analgesia period and randomized them to receive either 0.75% ropivacaine or 3% chloroprocaine in a 1:1 ratio. The primary outcome was the time to loss of cold sensation at the T4 level., Results: There was a significant difference between the two groups in the time to achieve loss of cold sensation (303, 95%CI 255 to 402 S vs. 372, 95%CI 297 to 630 S, p = 0.024). There was no significant difference the degree of motor block (p = 0.185) at the Th4 level. Fewer pregnant women required additional local anesthetics in the ropivacaine group compared to the chloroprocaine group (4.5% VS. 34.8%, p = 0.011). The ropivacaine group had lower intraoperative VAS scores (p = 0.023) and higher patient satisfaction scores (p = 0.040) than the chloroprocaine group. The incidence of intraoperative complications was similar between the two groups, and no serious complications were observed., Conclusions: Our study found that 0.75% ropivacaine was associated with less intraoperative pain treatment, higher patient satisfaction and reduced the onset time compared to 3% chloroprocaine in pregnant women undergoing urgent cesarean delivery during labor analgesia period. Therefore, 0.75% ropivacaine may be a suitable drug in pregnant women undergoing urgent cesarean delivery during labor analgesia period., Clinical Trial Number and Registry Url: The registration number: ChiCTR2200065201; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 31/10/2022., (© 2024. The Author(s).)

The population of non-alcoholic fatty liver disease (NAFLD) patients along with relevant advanced liver disease is projected to continue growing, because currently no medications are approved for treatment. Fecal microbiota transplantation (FMT) is believed a novel and promising therapeutic approach based on the concept of the gut-liver axis in liver disease. There has been an increase in the number of pre-clinical and clinical studies evaluating FMT in NAFLD treatment, however, existing findings diverge on its effects. Herein, we briefly summarized the mechanism of FMT for NAFLD treatment, reviewed randomized controlled trials for evaluating its efficacy in NAFLD, and proposed the prospect of future trials on FMT., Competing Interests: Conflict-of-interest statement: All the authors report having no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Previous studies have explored the median effective concentration (EC50) of ropivacaine for labor epidural analgesia in parturients with obesity. However, the clinical relevance of the 90% effective concentration (EC90) remains unclear. This study aimed to determine and compare the dose-response curve of epidural ropivacaine for labor analgesia between parturients with and without obesity. Methods: Parturients were divided into two groups based on body mass index (BMI): group N, consisting of parturients with BMI <30 kg/m 2 , and group O, consisting of parturients with BMI >30 kg/m 2 . Within each group, the patients were randomized to receive one of five concentrations (0.0375%, 0.075%, 0.1125%, 0.15%, or 0.1875%) of epidural ropivacaine for labor analgesia. Analgesia was induced with a loading dose of 15 mL of the assigned concentration. Visual analogue scale (VAS) scores were recorded at baseline and 30 min post-dose to calculate the response (%) using the formula [(baseline VAS pain score-VAS pain score at 30 min)/baseline VAS pain score] ×100%. The EC50 and EC90 values were determined via nonlinear regression analysis. Results: The EC50 and EC90 values of ropivacaine were 0.061% (95% confidence interval [CI], 0.056%-0.066%) and 0.177% (95% CI, 0.152%-0.206%) in group N and 0.056% (95% CI, 0.051%-0.061%) and 0.161% (95% CI, 0.138%-0.187%) in group O, respectively. No significant differences were observed in the EC50 and EC90 values between the two groups ( p -values = 0.121 and 0.351, respectively. Conclusion: In conclusion, within the parameters of this study, our findings suggest that obesity, characterized by a mean BMI value of 30.9, does not significantly influence the EC50 and EC90 values of epidural ropivacaine for labor analgesia. Further investigations are warranted to elucidate the dose-response relationship between ropivacaine and obesity with higher BMI values. Clinical trial registration: https://www.chictr.org.cn/showproj.html?proj=190747, Identifier ChiCTR2300073273., 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., (Copyright © 2024 Huang, Qiu, Wang, Jin and Xiao.)

Bicyclic hydantoinothiolactone (1), as the key intermediate for production of (+)-biotin, has been efficiently and high-stereoselectively synthesized from the cheap starting material l-cystine via nine steps in 44% overall yield. In this new practical synthesis, there are two characteristic steps worthy of note. One step is TMSOTf-catalyzed efficient cyanation of (3 S ,7a R )-6-benzyl-5-oxo-3-phenyltetrahydro-1 H ,3 H -imidazo[1,5- c ]thiazol-7-yl acetate, the other step is DBU-catalyzed rapid isomerization of trans -isomer to cis -isomer of the bicyclic hydantoinothiolactone., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Vimentin is a major type III intermediate filament protein that plays important roles in several basic cellular functions including cell migration, proliferation, and division. Although vimentin is a cytoplasmic protein, it also exists in the extracellular matrix and at the cell surface. Previous studies have shown that vimentin may exert multiple physiological effects in different nervous system injuries and diseases. For example, the studies of vimentin in spinal cord injury and stroke mainly focus on the formation of reactive astrocytes. Reduced glial scar, increased axonal regeneration, and improved motor function have been noted after spinal cord injury in vimentin and glial fibrillary acidic protein knockout (GFAP -/- VIM -/- ) mice. However, attenuated glial scar formation in post-stroke in GFAP -/- VIM -/- mice resulted in abnormal neuronal network restoration and worse neurological recovery. These opposite results have been attributed to the multiple roles of glial scar in different temporal and spatial conditions. In addition, extracellular vimentin may be a neurotrophic factor that promotes axonal extension by interaction with the insulin-like growth factor 1 receptor. In the pathogenesis of bacterial meningitis, cell surface vimentin is a meningitis facilitator, acting as a receptor of multiple pathogenic bacteria, including E. coli K1, Listeria monocytogenes, and group B streptococcus. Compared with wild type mice, VIM -/- mice are less susceptible to bacterial infection and exhibit a reduced inflammatory response, suggesting that vimentin is necessary to induce the pathogenesis of meningitis. Recently published literature showed that vimentin serves as a double-edged sword in the nervous system, regulating axonal regrowth, myelination, apoptosis, and neuroinflammation. This review aims to provide an overview of vimentin in spinal cord injury, stroke, bacterial meningitis, gliomas, and peripheral nerve injury and to discuss the potential therapeutic methods involving vimentin manipulation in improving axonal regeneration, alleviating infection, inhibiting brain tumor progression, and enhancing nerve myelination., Competing Interests: None

Objective: This study is designed to investigate the status of kinesiophobia and related factors in cancer patients with totally implantable venous access ports (TIAPs)., Methods: This is a cross-sectional study; all the participants were recruited from the Oncology Department and the Daytime Chemotherapy Center, Renji Hospital, Shanghai Jiao Tong University School of Medicine, from April 1 to May 31, 2021. The participants were interviewed by researchers using the self-made general information questionnaire and the Tampa Scale of Kinesiophobia-11 (TSK-11) scale, which allows the fear of movement to be quantified. Eligible patients were aged ≥ 18 years, confirmed with cancer, and implanted with a port. The logistic regression model was used to evaluate clinical factors and the risk of kinesiophobia., Results: A total of 282 patients were recruited (aged 58.0 ± 11.5 years), of which gastrointestinal cancer accounted for 54.6%, breast cancer accounted for 22.7%, lung cancer accounted for 11.3%, and other types accounted for 11.3%. The TSK-11 score of the 282 patients was 17.84 ± 6.06 points, 45.7% of the patients reported mild kinesiophobia (TSK-11 ≥ 18), 18.4% of the patients reported moderate to severe kinesiophobia (TSK-11 ≥ 25), and the highest score reached 34 points. Results of logistic regression analysis showed that exercise habits (P = 0.025), pain (P = 0.023), and foreign body sensation (P = 0.003) were the risk factors of kinesiophobia., Conclusion: Kinesiophobia is common in cancer patients with TIAPs, and it is closely related to the subjective experience of daily activities, which requires more attention and early intervention to reduce the potential adverse effects., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Interferon-induced protein-35 kDa (IFI35) was an antiviral protein induced by interferon (IFN)-γ, which plays an important role in the IFN-mediated antiviral signaling pathway. Here, we cloned and identified IFI35 in the chicken for the first time. Chicken IFI35 (chIFI35) contains an open reading frame (ORF) of 1,152 bp encoding a protein of 384 amino acids containing two conserved Nmi/IFI35 domain (NID) motifs. Tissue distribution analysis of chIFI35 in healthy and Newcastle disease (ND) virus-infected chickens indicated a positive correlation between chIFI35 mRNA transcription and ND viral loads in various tissues. The role of chIFI35 in regulation NDV replication were further assessed by up- or down-regulated chIFI35 expression in DF-1 cells transfected with plasmid harboring chIFI35, pCMV-3HA-chIFI35 or shRNA targeting chIFI35, pshRNA-chIFI35 plasmids. NDV replications in DF-1 cells were significantly reduced or slightly increased by over- or under-expression of the chIFI35 protein, respectively, indicating the role of chIFI35 in anti-NDV infection. Moreover, chIFI35 also involved in regulation of viral gene transcription and IFNs expression. The collected data were meaningful for research of chicken antiviral immunity and shed light on the pleiotropic antiviral effect of chIFI35 during NDV infection.

Estrogen deficiency induces cardiac dysfunction and increases the risk of cardiovascular disease in postmenopausal women and in those who underwent bilateral oophorectomy. Previous evidence suggests that puerarin, a phytoestrogen, exerts beneficial effects on cardiac function in patients with cardiac hypertrophy. In this study, we investigated whether puerarin could prevent cardiac hypertrophy and remodeling in ovariectomized, aortic-banded rats. Female SD rats subjected to bilateral ovariectomy (OVX) plus abdominal aortic constriction (AAC). The rats were treated with puerarin (50 mg·kg -1  ·d -1 , ip) for 8 weeks. Then echocardiography was assessed, and the rats were sacrificed, their heart tissues were extracted and allocated for further experiments. We showed that puerarin administration significantly attenuated cardiac hypertrophy and remodeling in AAC-treated OVX rats, which could be attributed to activation of PPARα/PPARγ coactivator-1 (PGC-1) pathway. Puerarin administration significantly increased the expression of estrogen-related receptor α, nuclear respiratory factor 1, and mitochondrial transcription factor A in hearts. Moreover, puerarin administration regulated the expression of metabolic genes in AAC-treated OVX rats. Hypertrophic changes could be induced in neonatal rat cardiomyocytes (NRCM) in vitro by treatment with angiotensin II (Ang II, 1 μM), which was attenuated by co-treatemnt with puerarin (100 μM). We further showed that puerarin decreased Ang II-induced accumulation of non-esterified fatty acids (NEFAs) and deletion of ATP, attenuated the Ang II-induced dissipation of the mitochondrial membrane potential, and improved the mitochondrial dysfunction in NRCM. Furthermore, addition of PPARα antagonist GW6471 (10 μM) partially abolished the anti-hypertrophic effects and metabolic effects of puerarin in NRCM. In conclusion, puerarin prevents cardiac hypertrophy in AAC-treated OVX rats through activation of PPARα/PGC-1 pathway and regulation of energy metabolism remodeling. This may provide a new approach to prevent the development of heart failure in postmenopausal women.

Background: Several studies have employed animal models to explore the association between microbiota and interleukin (IL) 10 signaling; however, limited information is available about the human microbiome., Aim: To characterize the microbiome in patients with IL10RA mutations and to explore the association between gut dysbiosis and disease severity., Methods: Fecal samples were collected from patients who were diagnosed with loss-of-function mutations in the IL10RA gene between January 2017 and July 2018 at the Children's Hospital of Fudan University. Age-matched volunteer children were recruited as healthy controls. Patients with Crohn's disease (CD) were used as disease controls to standardize the antibiotic exposure. Microbial DNA was extracted from the fecal samples. All analyses were based on the 16S rRNA gene sequencing data., Results: Seventeen patients with IL10RA mutations (IL10RA group), 17 patients with pediatric CD, and 26 healthy children were included. Both patients with IL10RA mutations and those with CD exhibited a reduced diversity of gut microbiome with increased variability. The relative abundance of Firmicutes was substantially increased in the IL10RA group ( P = 0.02). On further comparison of the relative abundance of taxa between patients with IL10RA mutations and healthy children, 13 taxa showed significant differences. The IL10RA-specific dysbiosis indices exhibited a significant positive correlation with weighted pediatric CD activity index and simple endoscopic score for CD., Conclusion: In patients with IL10RA mutations and early onset inflammatory bowel disease, gut dysbiosis shows a moderate association with disease severity., Competing Interests: Conflict-of-interest statement: The authors have no conflicts of interest to declare., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Vascular complications induced by diabetes constitute the principal cause of morbidity and mortality in diabetic patients. It has been reported that carvacrol (CAR) possesses a wide range of biological activities. The effects of CAR on diabetes-induced vasculopathy remain unknown. In this study, diabetic mice were created by the intraperitoneal injection of streptozotocin (STZ) in male C57BL/6 J mice to investigate whether CAR provided a protective effect against diabetes-induced vasculopathy and to investigate the underlying mechanisms. We found that CAR decreased blood glucose levels in diabetic mice. Moreover, CAR ameliorated diabetes-induced aortic morphological alterations, as evidenced by an increased thickness in the intima-media width and an increased number of vascular smooth muscle cells (VSMCs) layers. Further studies revealed that CAR inhibited hypercontractility in the aortas of diabetic mice and VSMCs in response to hyperglycemia, as evidenced by the relaxation of phenylephrine(PE)-induced vasoconstriction, the decreased expression of smooth muscle (SM)-α-actin, and the increased expression of Ki67 and proliferating cell nuclear antigen (PCNA). Furthermore, the PI3K/Akt signaling pathway was inhibited in the aortas of diabetic mice and VSMCs in response to hyperglycemia, while CAR treatment activated the PI3K/Akt signaling pathway. In conclusion, our results strongly suggest that CAR plays a protective role in diabetes-induced aortic hypercontractility, possibly by activating the PI3K/Akt signaling pathway. CAR is a potential drug for the treatment of diabetic vasculopathy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

The aim of this paper was to investigate the effect and mechanism of anemoside B4 on renal ischemia reperfusion injury in rats. A total of 50 rats were randomly divided into the model group(NS) and anemoside B4 low-dose(1.25 mg·kg~(-1)), medium-dose(2.5 mg·kg~(-1)) and high-dose(5 mg·kg~(-1)) groups after the right kidney was removed and the left kidney was ligated to make the ischemia reperfusion model. Another 10 rats were selected as sham operation group only for normal control group(NS, received normal saline). Automatic biochemical analyzer was used to measure serum blood urea nitrogen(BUN), creatinine(Cre), cerebrospinal fluid(CSF) and urinemicroalbumin(mALB) levels after 5 days of tail vein injection treament. Total urine protein and total urinary albu-min were calculated and kidney samples were collected. Histopathological changes of renal tissues were observed by PAS staining. Western blot analysis was performed to detect the protein expressions of TLR4 and NF-κB in renal inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway. The results showed that the levels of BUN, Cre, urinary total protein and urinary total albumin in the model group were significantly increased(P&lt;0.01), with severe renal tubule injury was serious, manifested by obvious expansion of renal tubules, more serious tubular proteins, and some tubular epithelial cells were exfoliated. At the same time, the expression of inflammatory factors related to NLRP3 pathway and TLR4/NF-κB pathway increased significantly(P&lt;0.01 or P&lt;0.05). The levels of BUN, Cre were reduced in different doses of anemoside B4(P&lt;0.05). The levels of total urinary protein and total urinary albumin were decreased in the low and high dose groups of anemoside B4.The level of total urinary albumin in the high-dose group of anemoside B4 was significantly reduced(P&lt;0.05).Renal tubular injury was alleviated, tubular epithelial cell exfoliation was reduced, and the expression of related inflammatory factors was reduced in different degrees(P&lt;0.01 or P&lt;0.05). This study showed that anemoside B4 could alleviate renal ischemia-reperfusion injury in rats. And its mechanism may be related to the inhibition of inflammatory factors related to response mediated by NLRP3 pathway and TLR4/NF-κB pathway by anemoside B4.

This paper was aimed to observe the effect of anemoside B4(hereinafter referred to as B4) on cisplatin-induced acute kidney injury in mice, and to investigate its possible mechanism in renal protection from inflammation and apoptosis aspects. Mice were divided into normal group, model group, dexamethasone positive group and B4 high, middle and low dose groups(5, 2.5, and 1.25 mg·kg~(-1 )doses). All the other mice groups except normal group were given with tail vein injection of cisplatin(15 mg·kg~(-1)) to induce acute kidney injury models. The drug administration was started on the day of modeling, and lasted for 4 days. After 1 hour of the last injection, orbital blood was collected. After the serum was separated, serum urea nitrogen(BUN), creatinine(Cre), total protein(TP), and albumin(ALB) were tested by using an automatic biochemical analyzer; the changes of kidney pathological morphology were observed by PAS staining; the protein expression levels of inflammatory factors including nucleotide binding oligomerization domain-like receptor(NLRP3), cysteinyl aspartate specific proteinase 1(caspase-1), interleukin-18(IL-18), interleukin-1β(IL-1β), tumor necrosis factor(TNF-α), and interleukin-6(IL-6) and apoptosis factors including p53, caspase-3, cleaved-caspase-3, Bcl-2 associated X protein(Bax), and B-cell lymphoma-2(Bcl-2) were analyzed by Western blot. The results showed that B4 significantly reduced the serum BUN and Cre contents, and alleviated pathological changes in renal tissues, such as the shedding and degeneration of renal tubular epithelial cells, tubulin tubule type. B4 significantly down-regulated the protein expressions of p53, Bax, cleaved-caspase-3 in the kidney and up-regulated the expression of Bcl-2/Bax. In model group, however, no significant up-regulation was observed in the protein expression levels of inflammatory cytokines(NLRP3, pro-caspase-1, IL-18, IL-1β, TNF-α, IL-6). The results suggested that B4 had a certain protective effect on cisplatin-induced acute kidney injury, and could activate p53 signaling pathway related apoptotic factors. B4 renal protective effect was mainly related to the regulation of p53 signaling pathway, while NLRP3 inflammasome and related inflammatory factors had no obvious response in this model.

Objective: Tracking the information on 1.69 million fetal cases across Guangxi Zhuang Autonomous Region (Guangxi) so as to study the occurrences of total and major birth defects in order to evaluate the ability on related prevention and control programs in Guangxi. Methods: Using the self-developed "Gui Women's System" to establish a database of 1.69 million fetal cases in Guangxi and to analyze the distribution of time, space and population, as well as the outcomes of pregnancy, using the big data. Results: During the 29 months of observation, the overall live birth rate was 99.25 % , with stillbirth rate during pregnancy as 0.44 % , stillbirth rate during birth as 0.02 % , and the 0-6 days mortality rate as 0.14 % . The total detection rate on birth defects was 197.63/10 000; the incidence rate was 103.04/10 000, the birth rate was 102.55/10 000. The overall discovery rate of major birth defects was 48.33/10 000, with the incidence rate as 783 000, the birth rate as 0.58/10 000. The discovery rates of major birth defects in 14 cities were between 35 and 68/10 000, and the birth rate dropped significantly to less than 1.00 in 10 000. Nationalities showed that the number of pregnant women with birth defects more than 50 000 would include Hui (9.68/10 000), Yao (9.57/10 000), and Jing (9.37/10 000). With the increasing age of gestation, number of birth defects, incidence of major birth defects also increased. Ninety-five percent of the major birth defects were found within <28 weeks and with the top 5 kinds of major birth defects as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). The top 5 major birth defects appeared as complicated congenital heart disease (9.11/10 000), alpha thalassemia (8.36/10 000), and 21-trisomy syndrome (7.85/10 000), beta thalassemia (5.32/10 000) and fetal edema syndrome (4.92/10 000). Conclusion: Programs leading to increase the rate on discovery of major birth defects were fundamental in effectively reducing the major birth defects.

Objective: To analyze the status and related factors of adverse pregnancy outcomes in pregnant women with syphilis infection in Guangxi Zhuang Autonomous Region. Methods: A total of 9378 pregnant women with syphilis infection who were diagnosed by Guangxi medical and health care institutions at all levels and were registered in the national "Management information system for mother-to-child transmission of AIDS, syphilis and hepatitis B" . The delivery date of these pregnant women were from 1 January 2014 to 31 December 2018, and their demographic characteristics, treatment, non-treponema pallidum titer, and pregnancy outcomes were collected. Multivariate logistic regression model was used to analyze the related factors of adverse pregnancy outcome. Results: The age of the pregnant women with syphilitic infection was (30.05±6.07) years old. There were 1 184 cases with an adverse pregnancy outcome. The incidence of adverse pregnancy outcome was 12.63%, and 83.30% (7 812 cases) of patients received syphilis treatment, of which 50.32% (3 931 cases) were treated with standard treatment. The results of multivariate analysis showed that, the probability of an adverse pregnancy outcome for a 35-year-old was higher than those of the <25 year old [ OR (95 %CI )=1.37(1.13-1.67)]. The possibility of the occurrence of an adverse pregnancy outcome in 1-2 times of delivery was lower than that of 0 times of delivery in the past, with the OR (95 %CI ) value was 0.81 (0.70-0.94). Compared with those who tested for syphilis in the early stages of pregnancy, patients with gestational weeks ≥ 28 weeks of initial examination were more likely to have adverse pregnancy outcomes, with the OR (95 %CI ) value was 1.54 (1.26-1.88). Compared with the first test titer level was <1:8, the probability of an adverse pregnancy outcome was higher in the titer of ≥1:8, with the OR (95 %CI ) value was 1.33 (1.12-1.57). There was a higher probability of an adverse pregnancy outcome in the untreated patients compared to the treatment of the syphilitic, with the OR (95 %CI ) value was 1.41(1.19-1.68). Patients with unregulated treatment were more likely to have adverse pregnancy outcomes than those with standardized treatment, with the OR (95 %CI ) value was 1.27 (1.09-1.47). Conclusion: Gestational weeks of first examination in pregnant women with syphilis infection, the first test titer, and the treatment condition were closely related to the occurrence of the adverse pregnancy outcome. Pregnant women with syphilis infection without treatment and unstandardized treatment were more likely to have adverse pregnancy outcomes than those of treatment and standardized treatment.

Objective: To study the clinical and nutritional characteristics of early-onset Crohn's disease (EO-CD) in China., Methods: Patients were defined as having EO-CD (age at diagnosis <10 y) or late-onset Crohn's disease (LO-CD; age at diagnosis of 10-17 y). Their characteristics, clinical, and nutritional data were collected at baseline and at each follow-up visit. Statistical analyses were used to compare differences in both groups., Results: From July 1993 to February 2017, of the 137 children enrolled, 68 (49.6%) had EO-CD and 69 (50.4%) had LO-CD. More patients with EO-CD than those with LO-CD presented with diarrhea, hematochezia, growth delay, anemia and skin disease, and had higher pediatric Crohn's disease activity index scores at diagnosis (all P < 0.05). Fewer patients with EO-CD achieved their first remission (42.6% vs 76.8%, P < 0.0001) during follow-up. Patients with EO-CD required a longer treatment time to reach remission (P = 0.0049) and had a higher mortality rate (P = 0.0133), as well as lower height and weight percentiles (P = 0.0200 and 0.0288, respectively), hemoglobin (P = 0.0185) and albumin levels (P = 0.0002), zinc (P = 0.0024) and iron (P = 0.0110) concentrations in blood at diagnosis., Conclusion: The EO-CD group had worse clinical outcomes and nutritional status than the LO-CD group., (© 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Objective: This study aimed to evaluate the stress distribution of the mandibular first molar with different thicknesses and heights of the axial wall restored by the endocrown with two marginal designs and thus provide a theoretical basis for selecting clinical preparation through the finite-element method., Methods: Two marginal endocrowns of the mandibular first molar with different axial-wall thicknesses (t=1, 2, 3 mm) and heights (h=2, 3, 4 mm) were established. Group A was the butt-joint design, whereas group B was the shoulder-surrounded design. After applying vertical and oblique loads , the size and distribution of the maximum principal stress and equivalent stress of residual tooth tissue were recorded., Results: The maximum principal stress and equivalent stress distribution of residual tooth tissue were similar among different models. Group A showed a lower maximum principal stress and equivalent stress than group B at the same thickness and height under vertical load. Meanwhile, under oblique load, the maximum principal stress values of groups A and B decreased with increased thickness at constant height. Group A showed lower equivalent stress than group B at the same thickness and height of 2 and 
3 mm. However, when the height was 4 mm, the trend was reversed., Conclusions: In mastication, when bearing the vertical force, the retention of the butt-joint marginal endocrown preferred to the shoulder-surrounded one. Given the higher axial wall of the shoulder-surrounded marginal endocrown, it showed better ability to bear the oblique force than the butt-joint one.

The pathogenesis of Alzheimer's disease (AD) is characterized by both accumulation of β-amyloid (Aβ) plaque and formation of neurofibrillary tangles in the brain. Recent evidence shows that autophagy activation may potently promote intracellular Aβ clearance. Thus targeting autophagy becomes a promising strategy for discovery of drug leads against AD. In the present study, we established a platform to discover autophagy stimulator and screened the lab in-house FDA-approved drug library. We found that anti-parasitic drug nitazoxanide (NTZ) was an autophagy activator and could efficiently improve learning and memory impairments in APP/PS1 transgenic mice. In BV2 cells and primary cortical astrocytes, NTZ stimulated autophagy and promoted Aβ clearance by inhibiting both PI3K/AKT/mTOR/ULK1 and NQO1/mTOR/ULK1 signaling pathways; NTZ treatment attenuated LPS-induced inflammation by inhibiting PI3K/AKT/IκB/NFκB signaling. In SH-SY5Y cells and primary cortical neurons, NTZ treatment restrained tau hyperphosphorylation through inhibition of PI3K/AKT/GSK3β pathway. The beneficial effects and related signaling mechanisms from the in vitro studies were also observed in APP/PS1 transgenic mice following administration of NTZ (90 mg·kg -1 ·d -1 , ig) for 100 days. Furthermore, NTZ administration decreased Aβ level and senile plaque formation in the hippocampus and cerebral cortex of APP/PS1 transgenic mice, and improved learning and memory impairments in Morris water maze assay. In conclusion, our results highlight the potential of NTZ in the treatment of AD.

Background: Diffuse midline glioma H3 K27M mutant is a new tumor entity described in the revised 2016 World Health Organization classification. It is most frequently observed in children and develops in midline structures, including the brainstem, thalamus, and spine. We describe a rare diffuse midline glioma with an H3 K27M mutation arising in the hypothalamus of an adult., Case Description: A 27-year-old woman was admitted to our department complaining of amenorrhea, polydipsia, and diuresis for the previous 3 months, and headache and lethargy for approximately 10 days. Computed tomography scan showed an oval isodense solid mass extending from the pituitary toward the suprasellar cistern. A gadolinium-enhanced magnetic resonance imaging (MRI) showed a strongly heterogeneous enhanced solid lesion and nonenhanced cystic lesion. The patient underwent surgery and chemoradiotherapy with temozolomide. Histologic and immunohistochemical analyses revealed H3 K27M-mutant diffuse midline glioma. The patient underwent another resection for a recurrent tumor 5 months after the first surgery. Three months after the second operation, the patient relapsed, with MRI revealing spinal cord and meningeal metastases; she died shortly afterward., Conclusions: Diffuse midline glioma with an H3 K27M mutation occurring in the hypothalamus of an adult is rare but should be considered in differential diagnoses. Because histone H3 K27M mutations are associated with aggressive clinical behavior and poor prognosis, molecular analyses should be used to determine the clinical and histopathologic features of such tumors. This will contribute to developing targeted drugs and gene therapy going forward., (Copyright © 2019. Published by Elsevier Inc.)

The present study aimed to evaluate the cardioprotective effects of a Rho‑kinase inhibitor, Y‑27632, and the underlying mechanisms. A rat model of myocardial ischemia‑reperfusion (I/R) injury was generated by ligation of the coronary artery, and global ischemia of isolated rat hearts was conducted using the Langendorff system. Staining with triphenyltetrazolium chloride (TTC) and hematoxylin and eosin was performed to analyze the myocardial infarct size and histopathological alterations of the I/R‑induced rat heart. In addition, coronary flow, myocardial contractility and an electrocardiogram were analyzed. The effects of Y‑27632 on inflammatory cytokines and cardiac enzymes in the serum were assessed by ELISA. The expression of apoptosis‑ and inflammation‑associated proteins was also analyzed via western blotting. Rats in the Y‑27632 group exhibited alleviated myocardial I/R injury according to TTC staining and histopathological diagnosis. Additionally, Y‑27632 restored the ST segment. The data of coronary flow and myocardial contractility in isolated rat hearts indicated that Y‑27632 improved heart function following I/R. The levels of inflammatory cytokines and cardiac enzymes in the serum were downregulated by Y‑27632. The mitogen‑activated protein kinase (MAPK) and nuclear factor (NF)‑κB signaling pathways were inhibited by Y‑27632. Furthermore, apoptosis‑associated protein expression in rats and the isolated hearts was effectively inhibited by Y‑27632. In conclusion, the findings of the present study indicated that Y‑27632 attenuated myocardial injury via inhibiting the activation of the MAPK and NF‑κB signaling pathways; thus, apoptosis and the inflammatory response were suppressed.

To explore the effects of captopril on calpain‑mediated apoptosis of myocardial cells and cardiac function in diabetic rats, 30 adult male Sprague‑Dawley rats were randomly divided into three groups: Negative control (NC group), untreated diabetic rats (DM group) and diabetic rats treated with captopril (Cap group). Diabetes was induced by streptozotocin injection. Captopril was intragastrically administered at a daily dose of 50 mg/kg for 12 weeks; the NC and DM groups received an equivalent volume of saline. After 12 weeks of treatment, left ventricular systolic pressure (LVSP), left ventricular end‑diastolic pressure (LVDEP), maximal rate of left ventricular pressure increase (+dp/dtmax), maximal rate of left ventricular pressure decrease (‑dp/dtmax) and left ventricular mass index (LVMI) were measured. The levels of calpain‑1, calpain‑2, B‑cell lymphoma (Bcl)‑2, Bcl‑2 associated protein X (Bax) and total caspase‑3 were detected in cardiac tissue by western blot analysis. The apoptotic index (AI) was assessed with a terminal deoxynucleotidyl transferase‑mediated dUTP nick‑end labeling assay. The ultrastructure of cardiac tissue was determined by transmission electron microscopy. Compared with the NC group, LVDEP and LVMI were increased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were decreased in the DM group. In the Cap group, LVDEP and LVMI were decreased, whereas LVSP, +dp/dtmax and ‑dp/dtmax were increased compared with the DM group. Bcl‑2 protein expression was decreased, whereas the levels of calpain‑1, calpain‑2, Bax and total caspase‑3 protein were increased in the DM group, compared with the NC group. Cap treatment increased Bcl‑2 protein expression and decreased calpain‑1, calpain‑2, Bax and total caspase‑3 protein expression compared with the DM group. Additionally, the AI was increased in the DM group compared with the NC group, and decreased in the Cap group compared with the DM group. Furthermore, ultrastructural examination demonstrated that myocardial cell injury was reduced in the Cap group compared with the DM group. Therefore, captopril improved myocardial structure and ventricular function, by inhibiting calpain‑1 and calpain‑2 activation, increasing Bcl‑2 expression, reducing Bax expression and subsequently inhibiting caspase‑3‑dependent apoptosis.

Objectives: To investigate the effects of dexmedetomidine (Dex) on injury of A549 cells induced by hypoxia/reoxygenation(H/R)and the influence of C/EBP homologous protein (CHOP) expression., Methods: Logarithmic growth phase A549 cells(it originated from alveolar type Ⅱ epithelial cell line) were randomly divided into 4 groups ( n =10):normoxic control group (N), Dex group (D), hypoxia/reoxygenation group (H), hypoxia/reoxygenation + Dex group(HD). At the beginning of modeling, 1 nmol/L Dex was puted into D and HD groups. N and D groups were cultured in the normoxic incubator for 30 h. H and HD group were incubated in the anoxic cultivation for 6 h, fo llowed by normoxic culture for 24 h. Then A549 cells were observed under the inverted microscope to observe the morphological changes. Cell activity was detected by cell counting Kit-8(CCK-8) and the apoptosis index(AI) was detected by in situ end labeling (TUNEL) method. The expression of CHOP、glucose-regulated protein of molecular weight 78 kDa (Grp78)、cysteinyl aspirate-specificprotease-3 (caspase-3) protein and CHOP、Grp78 mRNA were detected by Western blot and RT-PCR., Results: Compared with N group, the number of adherent cells in H group decreased significantly, and cell morphology changed. The absorbance value in H group decreased obviously ( P <0. 01). The AI value and expression of CHOP, Grp78, caspase-3 proteins and CHOP, Grp78 mRNA were significantly increased ( P <0.01). Compared with H group, the cell damage in HD group was decreased, the absorbance value increased ( P <0.01), the number of apoptosis cells decreased relatively ( P <0.01), the expression of CHOP, caspase-3 protein and CHOP mRNA decreased ( P <0. 01)., Conclusions: Dex has notable effects against H/R injury, which may be related to effective inhibition of apoptosis mediated by the CHOP's signal path.

Background: Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation., Methods and Results: We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production., Conclusions: We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional cardiomyocytes for disease modeling and in vitro drug screening., (© 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

To investigate the effects of dexmedetomidine (DEX) on hypoxia/reoxygenation (H/R) injury-induced cell apoptosis and caspase-12 expression, A549 cells were randomly divided into 4 groups: control group, DEX group, H/R group and DEX+H/R group. Cells of control and DEX groups were cultured in the normoxic incubator for 30 h. Cells of H/R and DEX+ H/R groups were incubated in the anoxic cultivation for 6 h, followed by normoxic culture for 24 h, and DEX (1 nmol/L) was added into the culture medium in DEX and DEX+H/R groups. Morphological changes were observed under the inverted microscope. Cell viability was detected by CCK-8. The apoptosis index (AI) of A549 cells was detected by TUNEL method. The activity of caspase-3 enzyme in cells was detected by using caspase-3 kit. The expressions of GRP78, caspase-12 protein and mRNA were determined by Western blot and RT-PCR respectively. Compared with control group, the morphological changes of the cultured cells were observed: some of the cell fusion occurred and the shape of the cells was multilateral; the cell viability was decreased significantly (P < 0.01), the number of apoptotic cells and the AI value, caspase-3 activity, and the expressions of GRP78, caspase-12 protein/mRNA were significantly increased (P < 0.01) in H/R group. While the administration of DEX alleviated the H/R injury-induced cell damage, obviously increased the cell viability (P < 0.01), significantly decreased the increment of apoptotic cells and the AI value induced by H/R injury (P < 0.01), and also dramatically decreased the H/R injury-induced high level of caspase-3 activity (P < 0.01) as well as high expression of caspase-12 protein and mRNA (P < 0.01). Taken together, the results suggest that DEX can effectively protect A549 cells from the H/R injury, which may be mediated by down-regulating the expression of caspase-12 and inhibiting cell apoptosis.

Previous studies have shown that increasing estradiol concentrations had a toxic effect on the embryo and were deleterious to embryo adhesion. In this study, we evaluated the physiological impact of estradiol concentrations on endometrial cells to reveal that serum estradiol levels probably targeted the endometrium in controlled ovarian hyperstimulation (COH) protocols. An attachment model of human choriocarcinoma (JAr) cell spheroids to receptive-phase endometrial epithelial cells and Ishikawa cells treated with different estradiol (10 -9  M or 10 -7  M) concentrations was developed. Differentially expressed protein profiling of the Ishikawa cells was performed by proteomic analysis. Estradiol at 10 -7  M demonstrated a high attachment rate of JAr spheroids to the endometrial cell monolayers. Using iTRAQ coupled with LC-MS/MS, we identified 45 differentially expressed proteins containing 43 significantly upregulated and 2 downregulated proteins in Ishikawa cells treated with 10 -7  M estradiol. Differential expression of C 3 , plasminogen and kininogen-1 by Western blot confirmed the proteomic results. C 3 , plasminogen and kininogen-1 localization in human receptive endometrial luminal epithelium highlighted the key proteins as possible targets for endometrial receptivity and interception. Ingenuity pathway analysis of differentially expressed proteins exhibited a variety of signaling pathways, including LXR/RXR activation pathway and acute-phase response signaling and upstream regulators (TNF, IL6, Hmgn3 and miR-140-3p) associated with endometrial receptivity. The observed estrogenic effect on differential proteome dynamics in Ishikawa cells indicates that the human endometrium is the probable target for serum estradiol levels in COH cycles. The findings are also important for future functional studies with the identified proteins that may influence embryo implantation., (© 2017 The authors.)

We report a novel mutation on the α2-globin gene, Hb Debao [α31(B12)Arg→Trp; HBA2: c.94A>T] detected in a Chinese family. This mutation gives rise to a previously undescribed hemoglobin (Hb) variant that was undetectable by electrophoretic or chromatographic methods. Hb Debao was associated with an α + -thalassemia (α + -thal) deletion [-α 3.7 (rightward)] producing a mild phenotype with significant microcytosis and hypochromia, while the combination of this mutation with an α 0 -thal deletion (-- SEA ) resulting in a severe form of Hb H (β4) disease, which is consistent with a thalassemic phenotype associated with the novel mutation.

The present study aimed to explore the stability, curability and sequelae of cases of Trichloroethylene (TCE) Hypersensitivity Syndrome (THS), and to investigate the causal allergens of THS. Two cases of THS were followed-up in the current study; both cases were healing following glucocorticoid therapy and were discharged >10 weeks prior to follow-up. A questionnaire investigation, health examination and patch test were performed. Allergens of TCE and its metabolites, including chloral hydrate, trichloroethanol (TCOH) and trichloroacetic acid, were applied in the patch test; 4 controls were included. The two subjects were experiencing itching, pigmentation and xerosis of the skin, and had abnormal results in the ophthalmology Schirmer I test and tear break-up time. The body temperature, liver function, superficial lymph nodes, blood, urine routine and autoimmune antibodies of two subjects were shown to be normal, and no new rashes had appeared. All mass concentration of chloral hydrate and TCOH were positive; 5.0% trichloroacetic acid was weakly positive, 0.5% trichloroacetic acid and all mass concentration of TCE were negative. All patch tests were negative in the 4 control subjects. The results suggest that THS was stable following treatment with glucocorticoid therapy. Dry eye syndrome may continue as a sequelae of THS. The patch test demonstrated that the mechanism underlying THS is delayed-type hypersensitivity induced by TCE. In addition, as the hypersensitivity state in a THS rehabilitee could be sustained over a long period of time, it suggests that the metabolites of TCE, not TCE itself, are responsible for THS. Therefore, patients with THS should avoid contact with TCE and its metabolites, and avoid using hypnotic and anticonvulsive drugs containing chloral hydra as the primary ingredient.

Purpose: Delta-like ligand 4 (DLL4) and Jagged1 (JAG1), 2 vascular Notch ligands, are involved in the process of tumor angiogenesis. The present study investigates their relationship with microvascularization and the prognostic effect in primary glioblastoma., Methods: Tumor tissues from 61 glioblastomas were analyzed using immunohistochemistry for DLL4/JAG1 expression and microvascular formations. The correlations between DLL4/JAG1 and microvascularization were analyzed. The survival probabilities were computed using the Kaplan-Meier method. The Cox proportional hazards regression model was used for multivariate analysis of time to progression (TTP) and overall survival (OS)., Results: The results showed increased DLL4 and JAG1 expression in glioblastoma tissues. Five types of basic microvascular formations, including microvascular sprouting, vascular cluster, vascular garland, glomeruloid vascular proliferation, and vasculogenic mimicry, were detected. Glioblastomas with the type I microvascular pattern (MVP) that displayed prominent microvascular sprouting and vascular clusters tended to have higher DLL4 expression, whereas those with the type II MVP that had numerous vascular garlands, glomeruloid vascular proliferations, and vasculogenic mimicries showed upregulated JAG1 expression. Univariate analysis documented that high DLL4 expression, high JAG1 expression, and type II (MVP) were statistically associated with reduced TTP and OS. Multivariate analysis confirmed high DLL4 expression, high JAG1 expression, and type II MVP as significant prognostic factors for both shorter TTP and OS, independent of age, Karnofsky performance scale, and other molecular markers (vascular endothelial growth factor, Ki67, and P53)., Conclusions: DLL4 and JAG1 may have opposing effects on tumor angiogenesis in glioblastoma. The Notch pathway may be a new target for antiangiogenic therapy in glioblastoma., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Delta-like ligand-4 (DLL4)-Notch signaling is known to play a pivotal role in the regulation of tumor angiogenesis. We had previously found that DLL4 was overexpressed, while Notch1 receptor, which binds to DLL4 during angiogenesis, was absent in the majority of human primary glioblastomas. Thus, DLL4-Notch signaling pathway in the regulation of tumor angiogenesis in primary glioblastoma remains unknown. Tumor tissues from 70 patients with primary glioblastoma were analyzed by immunohistochemistry for expression of components of DLL4-Notch signaling, vascular endothelial growth factor (VEGF), and microvessel density (MVD). Immunohistochemistry results showed that the positive staining of DLL4 and Notch4 was primarily distributed in tumor vascular endothelial cells but rarely detected in tumor cells. However, VEGF, hairy/enhancer of split-1 (HES1; a target gene of Notch signaling), and Notch1-3 expression was seen in both tumor vascular endothelial cells and tumor cells. Univariate analysis showed that the expression levels of VEGF and DLL4, HES1, and Notch4 in tumor endothelial cells were significantly associated with MVD in primary glioblastoma (P < 0.001). Binary logistic regression analysis showed that high expression levels of DLL4, HES1, and Notch4 in tumor endothelial cells were associated with a decrease of MVD in primary glioblastoma, while MVD increased with elevated VEGF expression in contrast. In addition, DLL4, Notch4, and HES1 expression were positively correlated in tumor vascular endothelial cells (P < 0.05). We conclude that the vascular DLL4-Notch4 signaling and VEGF signaling complementing each other plays an important role in the progression of tumor angiogenesis in primary glioblastoma. Graphical abstract A, positive staining of DLL4 in human kidney; B, positive staining of VEGF in human breast cancer; C, positive staining of CD34 in human lung cancer; D, positive staining of HES1 in human breast cancer; E-H, positive staining of Notch1-4: E-F in human lung cancer; G-H in human kidney.

Objective: To investigate the effect of dexmedetomidine (DEX) on expression of endoplasmic reticulum stress (ERS)-related cysteinyl aspirate specific proteinase-12 (Caspase-12) in lung ischemia/reperfusion (I/R) injury mice., Methods: Forty C57BL/6J mice were randomly divided into 4 groups:sham operation group (sham group),ischemia/reperfusion injury group (I/R group), normal salinecontrol group (NS group), ischemia/reperfusion + dexmedetomidine group (DEX group). Dexmedetomidine was infused intraperitoneally into the mice to stablish situ left pulmonary I/R injury mouse model. In NS group, the isometric dexmedetomidine was replaced by normal saline,other operations were as the same as the DEX group. After reperfusion 3 hours, the lung tissue wet/dry weight (W/D), the total lung water content (TLW) of the left lung tissues were determined. The lung tissue morphology changes were observed by light microscopy and the damage assessment(IQA) was taken. The structure changes and the apoptosis index (AI) of the lung tissues were evaluated by TUNEL method. The protein and mRNA expression of Caspase-12 and grp78 in lung tissues were detected by Western blot and reverse translate-PCR., Results: Compared with the sham group, the W/D, TLW, IQA, AI, lung tissue structure damages, and the expression of Caspase-12 and grp78 protein and mRNA obviously raised both in I/R group and NS group ( P <0.01 or P <0.05). Compared with I/R group, the W/D, TLW, IQA, AI of DEX group were all decreased, the demaged lung tissue morphology changes were significantly reduced, the protein and mRNA expression level of Caspase-12 and grp78 in DEX group were decreased ( P <0.01)., Conclusions: DEX can effectively relieve the lung I/R injuries in mice, which maybe associated with inhibition of pneumocyte apoptosis induced by ERS-related Caspase-12 pathway.

Despite the substantial data supporting the oncogenic role of Ack1, the predictive value and biologic role of Ack1 in hepatocellular carcinoma (HCC) metastasis remains unknown. In this study, both correlations of Ack1 expression with prognosis of HCC, and the role of Ack1 in metastasis of HCC were investigated in vitro and in vivo. Our results showed that Ack1 was overexpressed in human HCC tissues and cell lines. High Ack1 expression was associated with HCC metastasis and determined as a significant and independent prognostic factor for HCC after liver resection. Ack1 promoted HCC invasion and metastasis in vitro and in vivo. Mechanistically, we confirmed that Ack1 enhanced invasion and metastasis of HCC via EMT by mediating AKT phosphorylation. In conclusion, our study shows Ack1 is a novel prognostic biomarker for HCC and promotes metastasis of HCC via EMT by activating AKT signaling.

Object: Peritumoral brain edema (PTBE) is a common phenomenon associated with high-grade gliomas (HGGs). In this study, the authors investigated the expression of Notch delta-like ligand 4 (DLL4) and its correlation with PTBE and prognosis in patients with an HGG., Methods: Tumors from 99 patients with HGG were analyzed for DLL4 expression using immunohistochemistry. PTBE on preoperative MR images and the relationship between PTBE and DLL4 expression were evaluated. The effect of DLL4 on patient prognosis was assessed by using Kaplan-Meier survival and Cox proportional hazard models., Results: Immunohistochemistry results revealed that the expression of DLL4 was distributed primarily within the cytoplasm of tumor vascular endothelial cells and seldom detected in tumor cells. DLL4 expression was correlated positively with the degree of edema (r = 0.845 and p < 0.001, Spearman's test). In addition, DLL4 was an independent predictor of prognosis in patients with HGGs (p = 0.001)., Conclusions: DLL4 expression was correlated positively with the degree of PTBE and was an independent unfavorable prognostic indicator in patients with HGG.

Peritumoral edema (PTE), one of the main characteristics of malignant glioma, is a significant contributor to the morbidity and mortality from glioma, however, a recent systematic review suggested that controversy remains with regard to its prognostic value. To further determine whether PTE was a potential prognostic factor on routine pre-operative magnetic resonance imaging (MRI) for malignant glioma, the association between survival and PTE was investigated in the present retrospective review of 109 patients with newly diagnosed supratentorial malignant glioma using MRI data from these routine scans. The Kaplan-Meier method was used to calculate overall survival (OS) in univariate analysis, and COX proportional hazards model was applied to evaluate the effect of pre-operative MRI features on OS in multivariate analysis. The PTE extent, edema shape, degree of necrosis, enhancement extent, pathological grade, patient age, Karnofsky performance status (KPS) and post-operative chemoradiotherapy were associated with OS in the patients with malignant glioma on univariate analysis. Multivariate analysis indicated that the extent of PTE and degree of necrosis shown by pre-operative MRI were independent predictors of OS, in addition to pathological grade, patient age, KPS and post-operative chemoradiotherapy. Moreover, patients with two unfavorable factors (major edema and severe necrosis) exhibited a poorer OS compared with the remainder. In summary, PTE and degree of necrosis, which are easily determined from routine MRI, can be useful for predicting a poor clinical outcome in patients with newly diagnosed malignant glioma.

Purpose: To evaluate the influence of 3 different restorations on the fracture resistance of endodontically treated premolars with minor loss of dental defect in order to direct clinical design., Methods: Seventy-two recently extracted intact and single-rooted human mandibular premolars for orthodontic reason were collected and randomly divided into 3 groups (group A, B, C, n=24). Each group was respectively prepared into 1/3 defect of occlusal surface (group A), 1/2 defect of occlusal surface (group B) and 1/3 defect of proximal-occlusal surface model (group C). Then each group was divided into 3 subgroups with one restored with a light-curing composite resin(group A1, B1, C1), one restored with cast metal full crowns following a light-curing composite resin (group A2, B2, C2), and one restored with fiber posts and resin cores and cast full crowns after teeth preparations (group A3, B3, C3, n=8). Static loading tests were performed on each specimen until cracked.Fracture strength was tested and fracture patterns were examined. The data was analyzed using SPSS17.0 software package., Results: The fracture resistance of subgroup A2 was different when compared with subgroup A1 and subgroup A3. In group B and C, the fracture resistance of teeth in subgroup B2, B3, C2 and C3 were significantly higher than that in subgroup B1 and C1. There was no significant difference in the fracture mode of 3 restorations in group A, B and C., Conclusions: A composite resin combined with cast metal full crowns can be used as the first choice to restore endodontically treated premolars with proximal-occlusal 1/3 defects and occlusal defects that do not surpass 1/2 dimension of occlusion.

Purpose: To provide theoretical reference for maxillary anterior restoration designment in clinics by observing the masticatory stress distribution of the implant-bone interface and the displacement of implant., Methods: This study built simplified 3 dimensional finite models with different angles, which included partial implant (4.3 mm×11.5 mm), abutment and all ceramic crown (Zirconia) and combined with angle of implant A between the long axis of ideal implant and factual implant (0°, 5°, 10°, 15°, 20°, 25°), as well as angle of abutment B between the long axis of abutment and implant (0°, 5°,10°,15°,20°,25°). A force load of 178 N was applied 2 mm below the incisal edge on the palatal surface of the crown, with an approximately 130° angle to the long axis of the crown. The displacement of implant maximum principal stress value and distribution of the implant-bone interface were determined by using Ansys 13.0 software., Results: Sixteen 3-dimensional models of different implant restoration plan of implant dentures of maxillary incisor were built. When the angle of abutment was increasing with the same labial inclination of implant, the objective functions were enhanced. When the labial inclination of implant was increasing with the same angle of abutment, the objective functions were also improved. With the change of labial inclination of implant and angled abutment, the labial inclination of implant concentrated more than the angle of abutment on the objective functions. When the angle of abutment was between 0 degree and 20 degree, the amplitude of all the objective functions were gentle, while the labial inclination of implant and amplitude of all the objective functions were increased when the angle of abutment increased to 25 degree., Conclusions: A positive correlation is found between the value of stress of the bone around the implant, and the displacement of implant and the labial inclination of the implant and the angle of abutment. It is necessary to decrease the labial inclination of the implant and the angle of abutment, especially strictly control the labial inclination of the implant. Taking the stress and displacement into consideration, both of two angles ranging from 0 degree to 20 degree are the best optimal choice for the anterior implants. When both of two angles increase to much greater than 20 degree, the value of stress increase remarkably, which will decrease the chance of successful implant.

Objectives: Intrahepatic recurrence is the major cause of death among patients with hepatitis B virus (HBV)- related hepatocellular carcinoma (HCC) after curative surgical resection. Several approaches have been reported to decrease the recurrence rate. The objective of our study was to compare the clinical effects of transcatheter arterial chemoembolization (TACE) combined with interferon-alpha (IFN-α) therapy on recurrence after hepatic resection in patients with HBV-related HCC with that of TACE chemotherapy alone., Methods: We retrospectively analyzed the data from 228 patients who were diagnosed with HBV-related HCC and underwent curative resection between January 2001 to December 2008. The patients were divided into TACE (n = 126) and TACE-IFN-α (n = 102) groups for postoperative chemotherapy. The TACE regimen consisted of 5-fluorouracil (5-FU), cisplatin (DDP) , and the emulsion mixed with mitomycin C (MMC) and lipiodol. The recurrence rates, disease-free survival (DFS), overall survival (OS), and risk of recurrence were evaluated., Results: The clinicopathological parameters and adverse effects were similar between the 2 groups (P > 0.05). The median OS for the TACE- IFN-α group (36.3 months) was significantly longer than that of the TACE group (24.5 months, P < 0.05). The 3-and 5-year OS for the TACE-IFN-α group were significantly longer than those of the TACE group (P < 0.05) and the recurrence rate was significantly lower (P < 0.05). The TACE and IFN-α combination therapy, active hepatitis HBV infection, the number of tumor nodules, microvascular invasion, liver cirrhosis, and the BCLC stage were independent predictors of OS and DFS., Conclusions: The use of the TACE and IFN-α combination chemotherapy after curative hepatic resection safely and effectively improves OS and decreases recurrence in patients with HBV-related HCC who are at high risk. Our findings can serve as a guide for the selection of postoperative adjuvant chemotherapy for patients with HBV-related HCC who are at high risk of recurrence.

Glioblastoma is a highly aggressive brain tumor. Aberrant Notch pathway has been implicated in the formation and progression of glioblastoma. The present study attempted to investigate the expression of Notch ligand Jagged1 and its association with patient outcome in primary glioblastoma. Tumor tissues from 82 patients with primary glioblastoma were analyzed using immunohistochemistry for Jagged1 expression. Relationships between Jagged1 expression and clinical features (age, gender, KPS, symptom duration, extent of resection and Ki67 index) were evaluated. The prognostic value of Jagged1 was assessed using the Kaplan-Meier survival estimates and the Cox proportional hazard models. Immunohistochemistry results showed markedly increased Jagged1 expression in glioblastoma tissues compared to adjacent non-neoplastic brain tissues. Univariate analysis documented that high Jagged1 expression in tumor cells (TC) and endothelial cells (EC) were both statistically associated with reduced time to progression (TTP) (P < 0.001 for TC, P = 0.001 for EC) and overall survival (OS) (P < 0.001 for TC, P = 0.003 for EC) in primary glioblastoma. The median TTP (P < 0.001) and OS (P = 0.001) were higher in patients with dual-low Jagged1 expression in TC and EC compared to those in patients with non-dual Jagged1 expression and dual high expression. By multivariate survival analysis, we found that high Jagged1 expression in both tumor cells and endothelial cells was independent unfavorable prognostic factors TTP (P < 0.001 for TC, P < 0.001 for TC) and OS (P < 0.001 for TC, P < 0.001 for TC) in primary glioblastoma patients. Jagged1-Notch signaling plays an important role in the progress of glioblastoma. Jagged1 expression may be used as an independent prognosis factor in patients with glioblastoma.

Fipronil is an effective insecticide, but it presents highly toxic effects in nontarget aquatic organisms. The present study examined the enantioselective toxicity and degradation of fipronil enantiomers in a freshwater algae Scenedesmus obliguus suspension. There was a substantial difference in the acute toxicity of the enantiomers to S. obliguus, with 72-h median effective concentrations (EC50s) of 0.29 mg L(-1) and 1.50 mg L(-1) for the R-fipronil and S-fipronil, respectively. The influences on the concentration of chlorophyll a, chlorophyll b, and carotenoids were determined, and the effects of fipronil on the concentration of chlorophyll a and chlorophyll b were also enantioselective. The degradation of fipronil in algae suspension was enantioselective, with half-lives for R-fipronil and S-fipronil of 2.9 d and 3.2 d, respectively, and the enantiomer fraction reaching 0.65 at the day 17. The enantiomeric differences should be taken into consideration for fipronil risk assessment., (© 2014 SETAC.)

This study aimed to characterize lymph node metastasis and determine its clinical significance in the surgical treatment of gastric cancer. The medical charts of 920 gastric cancer patients who underwent radical surgical resection between March, 2010 and March, 2013, were retrospectively reviewed and statistically analyzed. Lymphatic metastasis was observed in 69.6% of the patients (640/920). The frequency of lymph node metastasis in patients with early-stage gastric cancer was 21.4% (18/84). Lymph node metastasis was observed in all the patients with stage IIIC-IV gastric cancer. The incidence of lymph node metastasis was higher among patients with tumors >7 cm in size. The most frequently affected lymph nodes in patients with proximal, central and distal gastric cancer were station no. 1 (34.2%), no. 3 (33.8%) and no. 6 (34.3%) lymph nodes, respectively. The frequency of lymph node metastasis in patients with Borrmann type IV cancer was significantly higher compared to that in patients with other Borrmann type cancers. Our study further demonstrated that lymphatic metastasis is closely correlated with TNM stage, location, depth of invasion and size of gastric tumors. Therefore, we recommend that a sufficient number of lymph nodes be examined from each patient to determine the extent of lymph node dissection based on Borrmann type, location, size, depth of invasion and histology of the cancer.

Mesohepatectomy is considered a feasible option for patients with centrally located hepatocellular carcinoma (HCC). However, mesohepatectomy is a technically demanding and less frequently used procedure. In this study, we summarized the surgical experience and evaluated the clinical outcomes of mesohepatectomy in 24 patients with centrally located HCC. Of these patients, 9 were treated with hepatectomy of Couinaud's segments IV, V and VIII with concurrent cholecystectomy; 8 underwent resection of segments IVb, V and VIII, including 7 patients who also received a cholecystectomy; 4 underwent hepatectomy of segments IVa, V and VIII; and 3 patients were treated with hepatectomy of segments I, IV, V and VIII, with concurrent cholecystectomy. The Pringle maneuver was used on 17 patients during hepatectomy. Total hepatic vascular exclusion (HVE) was performed on 3 patients and HVE was not used on 4 patients. The average mesohepatectomy operative time was 238 min and the average intraoperative blood loss was 480 ml (200-2,200 ml). There was no intraoperative mortality and the postoperative morbidity rate was 25% (6/24). The 1- and 3-year overall survival rates were 76 and 46%, respectively. Therefore, mesohepatectomy is a safe and effective surgical procedure for the treatment of centrally located HCC and HVE during mesohepatectomy for centrally located HCC is crucial to the success of the operation and postoperative patient recovery.

Delta-like ligand 4 (DLL4), 1 of the 5 known Notch ligands, is involved in a variety of tumor initiation and progression, particularly in the process of tumor angiogenesis. However, the clinical and prognostic significance of DLL4 in glioblastoma have not been fully elucidated.Tumor tissues from 69 glioblastoma patients were analyzed using immunohistochemistry for DLL4 expression. Peritumoral brain edema (PTBE) on preoperative magnetic resonance imaging of these patients and the relationship with DLL4 expression were evaluated. The effect on prognosis was assessed by using the Kaplan-Meier survival and the Cox proportional hazard model.The results showed that elevated DLL4 expression was primarily distributed in the cytoplasm of tumor vascular endothelial cells and rarely detected in tumor cells. Univariate analysis indicated significant correlation of high DLL4 expression with shorter time to progression (TTP) (P < 0.001) and overall survival (OS) (P < 0.001) in glioblastoma. Multivariate analysis confirmed high DLL4 expression as an unfavorable prognostic indicator for TTP (P < 0.001) and OS (P < 0.001), independent of age, gender, symptom duration, resection degree, and PTBE. Importantly, the study also found that DLL4 expression was positively related with PTBE (Spearman's test: r = 0.845, P < 0.001). A multiple linear regression model was constructed to confirm that the positive index of DLL4 was associated with an increase in maximum extent of PTBE (P < 0.001).It is thus concluded that DLL4 is correlated with PTBE and may be useful for predicting prognosis in glioblastoma.

The enantioselective acute toxicity to earthworms of racemic fipronil and its individual enantiomers was studied. R-(-)-fipronil was approximately 1.5 times more toxic than the racemate and approximately 2 times more toxic than S-(+)-fipronil after 72 and 96 h of exposure, respectively. Assays of fipronil enantiomer bioaccumulation and degradation in earthworms were conducted. The bio-concentration factors (BCFs) were slightly different between the two enantiomers. The enantiomeric fraction (EF) values in earthworms in the bioaccumulation period were approximately 0.5, which indicated there was no enantioselective bioaccumulation. In contrast, the degradation of fipronil in earthworms was enantioselective: the t1/2 values for R- and S-fipronil were 3.3 and 2.5 days, respectively, in natural soil, and 2.1 and 1.4 days, respectively, in artificial soil. The results of soil analyses showed that the degradation of fipronil was not enantioselective, which suggested that the enantioselectivity of fipronil in earthworms results from the organism's metabolism. The study also demonstrated that the presence of earthworms could accelerate the degradation of fipronil in soil., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Purpose: Peripherally inserted central catheter (PICC) spontaneous dislodgment is insidious in onset and prone to cause complications. We performed a prospective cohort study to examine the incidence, risk factors and clinical results of PICC spontaneous dislodgment in oncology patients to facilitate successful early diagnosis, prophylaxis and management., Patients and Methods: Consecutive oncology patients, undergoing placement of PICCs, were enrolled and prospectively followed up until their catheters were removed or PICC spontaneous dislodgment presented. The patients with PICC spontaneous dislodgment or catheter-associated thrombosis (CRT) were followed up for an extra three months from the date of diagnosis. The main endpoint was PICC spontaneous dislodgment, and the sub-endpoints were CRT and catheter in-place time. The PICC insertion team, nurses, interventional radiologists and oncology doctors collected longitudinal data., Results: Over a total of 60,894 days of cumulative follow-up, 21 out of 510 PICCs presented spontaneous dislodgment, leading to an incidence rate of 4.12%. The CRT rate of the group with PICC spontaneous dislodgment was much higher than that of the group without PICC spontaneous dislodgment (RR=17.46, 95% CI: 8.29-36.82, p=1.09×10(-17)). Five baseline exposure factors, including primary lung cancer, metastatic lung cancer, chest radiotherapy, vigorous coughing and severe vomiting, were significant risk factors of PICC spontaneous dislodgment. Basilic vein access (odds ratio [OR]=0.39, 95% CI: 0.16-0.95, P=0.04) was a protective factor against PICCSD in univariate analysis. Among these factors, the independent significant risk factors were vigorous coughing (OR=6.14, 95% CI: 1.70-22.16, P=0.01) and severe vomiting (OR=3.70, 95% CI: 1.28-10.68, P=0.02)., Conclusion: The incidence rate of PICC spontaneous dislodgment is 4.12% (0.34 per 1000 catheter-days); PICC spontaneous dislodgment significantly increases the risk of CRT and shortens catheter in-place time. Vigorous coughing and severe vomiting were independent risk factors of PICC spontaneous dislodgment among oncology patients., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

A halophilic archaeal strain, GX48(T), was isolated from the Gangxi marine solar saltern near Weihai city in Shandong Province, China. Cells of the strain were rod-shaped, stained Gram-negative and formed red-pigmented colonies. Strain GX48(T) was able to grow at 25-50 °C (optimum 37 °C), in the presence of 1.4-4.8 M NaCl (optimum 2.6 M NaCl), with 0-1.0 M MgCl2 (optimum 0.05 M MgCl2) and at pH 5.5-9.5 (optimum pH 7.0). Cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 8 % (w/v). The major polar lipids of the strain were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and two major glycolipids chromatographically identical to those of Natronoarchaeum mannanilyticum YSM-123(T) and Natronoarchaeum philippinense 294-194-5(T). 16S rRNA gene analysis revealed that strain GX48(T) had two dissimilar 16S rRNA genes and both of them were phylogenetically related to those of the two current members of the genus Natronoarchaeum (96.2-98.3 % similarities). The rpoB' gene sequence similarities between strain GX48(T) and Natronoarchaeum mannanilyticum YSM-123(T) and Natronoarchaeum philippinense 294-194-5(T) were 96.0 % and 94.7 %, respectively. The DNA G+C content of strain GX48(T) was 66.2 mol%. Strain GX48(T) showed low DNA-DNA relatedness with the two members of the genus Natronoarchaeum. It was concluded that strain GX48(T) ( = CGMCC 1.10388(T) = JCM 17119(T)) represents a novel species of the genus Natronoarchaeum, for which the name Natronoarchaeum rubrum sp. nov. is proposed. An emended description of the genus Natronoarchaeum is also presented.

Halophilic archaeal strain GX31(T) was isolated from a marine solar saltern of China. The cells of the strain were rod-shaped and lysed in distilled water, stain Gram-negative and formed red-pigmented colonies. It was neutrophilic, and required at least 0.9 M NaCl and 0-1.0 M MgCl2 for growth under the optimum growth temperature of 37 °C. The major polar lipids of the strain were phosphatidylglycerol (PG), PG phosphate methyl ester, PG sulphate, and two major glycolipids chromatographically identical to sulphated mannosyl glucosyl diether (S-DGD-1) and mannosyl glucosyl diether (DGD-1), respectively. Trace amounts of two unidentified lipids were also detected. On the basis of 16S rRNA gene sequence analysis, strain GX31(T) was closely related to the members of Halobellus of the family Halobacteriaceae with similarities of 94.1-98.7 %. Strain GX31(T) showed 89.8-95.4 % of the rpoB' gene similarity to the members of Halobellus. The DNA G+C content of strain GX31(T) was 66.8 mol%. Strain GX31(T) showed low DNA-DNA relatedness with two most related members of the genus Halobellus. The phenotypic, chemotaxonomic and phylogenetic properties suggest that strain GX31(T) represent a novel species of the genus Halobellus, for which the name Halobellus litoreus sp. nov. is proposed. The type strain is GX31(T) (=CGMCC 1.10387(T) = JCM 17118(T)).