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Background and purpose: Acute kidney injury (AKI) is a common serious complication in sepsis patients with a high mortality rate. This study aimed to develop and validate a predictive model for sepsis associated acute kidney injury (SA-AKI). Methods: In our study, we retrospectively constructed a development cohort comprising 733 septic patients admitted to eight Grade-A tertiary hospitals in Shanghai from January 2021 to October 2022. Additionally, we established an external validation cohort consisting of 336 septic patients admitted to our hospital from January 2017 to December 2019. Risk predictors were selected by LASSO regression, and a corresponding nomogram was constructed. We evaluated the model's discrimination, precision and clinical benefit through receiver operating characteristic (ROC) curves, calibration plots, decision curve analysis (DCA) and clinical impact curves (CIC) in both internal and external validation. Results: AKI incidence was 53.2% in the development cohort and 48.2% in the external validation cohort. The model included five independent indicators: chronic kidney disease stages 1 to 3, blood urea nitrogen, procalcitonin, D-dimer and creatine kinase isoenzyme. The AUC of the model in the development and validation cohorts was 0.914 (95% CI, 0.894-0.934) and 0.923 (95% CI, 0.895-0.952), respectively. The calibration plot, DCA, and CIC demonstrated the model's favorable clinical applicability. Conclusion: We developed and validated a robust nomogram model, which might identify patients at risk of SA-AKI and promising for clinical applications.

Background: Operating rooms are complex working environments with high workloads and high levels of cognitive demand. The first surgical count which occurs during the chaotic preoperative stage and is considered a critical phase, is a routine task in ORs. Interruptions often occur during the first surgical count; however, little is known about the first surgical counting interruptions. This study aimed to observe and analyse the sources, outcomes, frequency of the first surgical counting interruptions and responses to interruptions., Methods: A retrospective observational study was carried out to examine the occurrence of the first surgical counting interruptions between 1st August 2023 and 30th September 2023. The data were collected using the "Surgical Counting Interruption Event Form", which was developed by the researchers specifically for this study., Results: A total of 66 circulating nurses (CNs) and scrub nurses (SNs) were observed across 1015 surgeries, with 4927.8 min of surgical count. The mean duration of the first surgical count was 4.85 min, with a range of 1.03 min to 9.51 min. In addition, 697 interruptions were identified, with full-term interruptions occurring an average of 8.7 times per hour. The most frequent source of interruption during the first surgical counts was instruments (N = 144, 20.7%). The first surgical counting interruptions mostly affected the CN (336 times; 48.2%), followed by the ORNs (including CNs and SNs) (243 times; 34.9%) and the SN (118 times; 16.9%). Most of the outcomes of interruptions were negative, and the majority of the nurses responded immediately to interruptions., Conclusions: The frequency of the first surgical counting interruption is high. Managers should develop interventions for interruptions based on different surgical specialties and different nursing roles., (© 2024. The Author(s).)

Introduction: Determining the causal relationship between polycystic ovary syndrome (PCOS) and gestational diabetes mellitus (GDM) holds significant implications for GDM prevention and treatment. Despite numerous observational studies suggesting an association between PCOS and GDM, it remains unclear whether a definitive causal relationship exists between these two conditions and which specific features of PCOS contribute to increased incidence of GDM., Methods: The causal relationship between polycystic ovary syndrome (PCOS), its characteristic indices, and gestational diabetes mellitus (GDM) was investigated using a two-sample Mendelian randomization study based on publicly available statistics from genome-wide association studies (GWAS). The inverse-variance weighted method was employed as the primary analytical approach to examine the association between PCOS, its characteristic indices, and GDM. MR Egger intercept was used to assess pleiotropy, while Q values and their corresponding P values were utilized to evaluate heterogeneity. It is important to note that this study adopts a two-sample MR design where PCOS and its characteristic indices are considered as exposures, while GDM is treated as an outcome., Results: The study results indicate that there is no causal relationship between PCOS and GDM (all methods P > 0.05, 95% CI of OR values passed 1). The IVW OR value was 1.007 with a 95% CI of 0.906 to 1.119 and a P value of 0.904. Moreover, the MR Egger Q value was 8.141 with a P value of 0.701, while the IVW Q value was also 8.141 with a P value of 0.774, indicating no significant heterogeneity. Additionally, the MR Egger intercept was 0.0004, which was close to zero with a P value of 0.988, suggesting no pleiotropy. However, the study did find a causal relationship between several other factors such as testosterone, high-density lipoprotein, sex hormone-binding globulin, body mass index, waist-hip ratio, apolipoprotein A-I, number of children, diabetes illnesses of mother, father and siblings, hemoglobin A1c, fasting insulin, fasting blood glucose, years of schooling, and GDM based on the IVW method., Conclusion: We observed no association between genetically predicted PCOS and the risk of GDM, implying that PCOS itself does not confer an increased susceptibility to GDM. The presence of other PCOS-related factors such as testosterone, high-density lipoprotein, and sex hormone-binding globulin may elucidate the link between PCOS and GDM. Based on these findings, efforts aimed at preventing GDM in individuals with PCOS should prioritize those exhibiting high-risk features rather than encompassing all women with PCOS., 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 Guixue, Yifu, Xiaofeng, Qian, Yuan, Wen, Conghui and Zuobin.)

The potential protective effect of basic fibroblast growth factor (BFGF) on the cardiovascular system has been proposed previously, however, its effect on calcific aortic valve disease (CAVD) and underlying mechanisms have not been elucidated. The valvular interstitial cell (VIC) were isolated from porcine aortic valve leaflets. To investigate the effect of BFGF on osteogenic differentiation of VIC, the osteogenic induced medium (OIM) and BFGF were added. The protein expression level was detected by Western blot, and apoptosis was determined by flow cytometry. The effect of BFGF on CAVD process in vivo was assessed by a rat CAVD model, which was identified by echocardiography and Alizarin red staining. The expression level of BFGF in the aortic valve and serum were significantly upregulated in CAVD patients compared to control group. In addition, exogenous BFGF injection attenuates CAVD process in vivo. The protein markers of osteogenic differentiation, endoplasmic reticulum stress (ERS), and apoptosis were significantly upregulated by culture with OIM. On the contrary, the aforementioned proteins were suppressed after adding 100 ng/mL of BFGF. Inhibition of PI3K/Akt and ERK1/2 pathways by specific inhibitors abolished the protective effect of BFGF. In conclusion, BFGF could alleviate the VIC calcification by inhibiting ERS-mediated apoptosis, which is partly regulated by activation of the PI3K/Akt and ERK1/2 signaling pathways. BFGF may provide a potential avenue for CAVD therapy., 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 © 2023 Elsevier Inc. All rights reserved.)

Clinical prediction models play an important role in the field of medicine. These can help predict the probability of an individual suffering from disease, complications, and treatment outcomes by applying specific methodologies. Polycystic ovary syndrome (PCOS) is a common disease with a high incidence rate, huge heterogeneity, short- and long-term complications, and complex treatments. In this systematic review study, we reviewed the progress of clinical prediction models in PCOS patients, including diagnosis and prediction models for PCOS complications and treatment outcomes. We aimed to provide ideas for medical researchers and clues for the management of PCOS. In the future, models with poor accuracy can be greatly improved by adding well-known parameters and validations, which will further expand our understanding of PCOS in terms of precision medicine. By developing a series of predictive models, we can make the definition of PCOS more accurate, which can improve the diagnosis of PCOS and reduce the likelihood of false positives and false negatives. It will also help discover complications earlier and treatment outcomes being known earlier, which can result in better outcomes for women with PCOS., (© 2023. The Author(s).)

In the context of the rapid rise of the village revitalization in China, the study examines the impact of grassroots autonomous organizations embedding level and farmer non-agriculture employment on the farmer homestead exit behavior. Based on 421 household surveys in Qionglai, this study obtained three results through empirical analysis. (1) The system embedding level of grassroots autonomous organization and the interests embedding level of grassroots autonomous organization have a significant positive impact on the farmer homestead withdrawal behavior, but the emotion embedding level of grassroots autonomous organizations has a significant negative impact on the farmer homestead withdrawal behavior. (2) The farmer non-agriculture employment level is beneficial for the farmer homestead exit behavior. (3) Further mechanism analysis shows that the non-agricultural employment level plays an inhibitory role in the positive influence of grassroots organizations to mobilize farmers to exit homestead. Therefore, it is suggested that when mobilizing farmers to voluntarily withdraw from the homestead, grassroots organizations should actively improve their embedding level, improve the construction of farmers' social network, and accelerate the accumulation of farmers' material capital., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Chronic allograft dysfunction(CAD) is the leading cause of graft loss in kidney transplant recipients (KTRs). Inflammatory process is believed to be one of the major contributors to CAD. The aim of this study is to explore the anti-inflammatory effect of vitamin D (VD) supplementation in KTRs and its role in the graft function improvement(protection)., Methods: A retrospective cohort of 39 KTRs with chronic antibody mediated rejection(CAMR)or stable renal function and a prospective cohort of 42 KTRs treated or untreated with VD were enrolled. Serum levels of vitamin D metabolism and serum inflammatory cytokines, renal graft function, and routine blood biomarkers were tested and dynamically tracked within 12 months post-transplant., Results: Compared with the stable group, the CAMR group exhibited significantly elevated serum levels of inflammatory cytokines IL-1β, IFN-γ, IL-2, IL-10, IP-10, and HMGB1 (P <0.05). The supplementation of vitamin D effectively increased the serum concentration of vitamin D in kidney transplant recipients (KTRs) in the treated group. During the course of treatment, the treated group exhibited a gradual increase in eGFR levels, which were significantly higher than those observed in the untreated group at 12 months post-transplant (p<0.05). Notably, as eGFR improved, there was a significant decrease in levels of IL-1β, IFN-γ, IL-2, IL-10, IP-10 and HMGB1 in the treated group compared to the untreated group (P<0.05)., Conclusion: This study confirmed that immune-inflammation is a crucial factor in the development of CAD in KTRs.VD deficiency impairs its anti-inflammatory activity. By assisting in the regulation of excessive immune inflammation and restoration of immune homeostasis, effective VD supplementation contributes to protection and maintenance of graft function in KTRs., 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 © 2023 Bai, Li, Hu, Zou, An, Wang and Shi.)

There have been few reports on the substituent effect of main-group-element corrole complexes as ligand-centered homogeneous electrocatalysts for the hydrogen evolution reaction (HER). The key to comprehend the catalytic mechanism and develop efficient catalysts is the elucidation of the effects of electronic structure on the performance of energy-related small molecules. In this work, the "push-pull" electronic effect of the substituents on electrocatalytic HER of phosphorus corroles was investigated by using 5,10,15-tris(phenyl) corrole phosphorus (1P), 10-pentafluorophenyl-5,15-bis(phenyl) corrole phosphorus (2P), 10-phenyl-5,15-bis(pentafluorophenyl) corrole phosphorus (3P), 5,10,15-tris(pentafluorophenyl) corrole phosphorus (4P) complexes bearing hydroxyl axial ligands and different numbers of fluorine atoms on the meso-aryl substituents. The results revealed that the catalytic HER activity of phosphorus corroles decreased with the increasing of fluorine atom numbers, it follows in the order 1P>2P>3P>4P. Density functional theory (DFT) calculations show that the corrole 1P has the lowest free energy barrier in catalytic HER., (© 2023 Wiley-VCH GmbH.)

Objective: To determine the prevalence of mitochondrial diseases (MD) in Hong Kong (HK) and to evaluate the clinical characteristics and genetic landscape of MD patients in the region., Methods: This study retrospectively reviewed the phenotypic and molecular characteristics of MD patients from participating public hospitals in HK between January 1985 to October 2020. Molecularly and/or enzymatically confirmed MD cases of any age were recruited via the Clinical Analysis and Reporting System (CDARS) using relevant keywords and/or International Classification of Disease (ICD) codes under the HK Hospital Authority or through the personal recollection of treating clinicians among the investigators., Results: A total of 119 MD patients were recruited and analyzed in the study. The point prevalence of MD in HK was 1.02 in 100,000 people (95% confidence interval 0.81-1.28 in 100,000). 110 patients had molecularly proven MD and the other nine were diagnosed by OXPHOS enzymology analysis or mitochondrial DNA depletion analysis with unknown molecular basis. Pathogenic variants in the mitochondrial genome (72 patients) were more prevalent than those in the nuclear genome (38 patients) in our cohort. The most commonly involved organ system at disease onset was the neurological system, in which developmental delay, seizures or epilepsy, and stroke-like episodes were the most frequently reported presentations. The mortality rate in our cohort was 37%., Conclusion: This study is a territory-wide overview of the clinical and genetic characteristics of MD patients in a Chinese population, providing the first available prevalence rate of MD in Hong Kong. The findings of this study aim to facilitate future in-depth evaluation of MD and lay the foundation to establish a local MD registry., (© 2023. The Author(s).)

Background: Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)., Methods: We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir)., Results: A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%)., Conclusions: Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.)., (Copyright © 2022 Massachusetts Medical Society.)

Aims/introduction: Emerging evidence has suggested the detrimental role of oxidative stress in aggravating ischemia and reperfusion (IR) injury in diabetic livers. Interplay between oxidative stress and mitophagy has been shown. However, the role and mechanism of mitophagy in regulating oxidative stress and IR injury in diabetic livers remain unclear., Materials and Methods: Wild-type and db/db (DB) mice were subjected to a partial warm liver IR model. Liver injury, oxidative stress, mitophagy and related molecular pathways were analyzed., Results: Here, we found that increased liver IR injury was observed in DB mice, as evidenced by higher levels of serum alanine aminotransferase and serum aspartate, worsened liver architecture damage and more hepatocellular death. DB mice also showed increased mitochondrial oxidative stress. Mitochondrial reactive oxygen species scavenge alleviated liver IR injury in DB mice. Mechanistic analysis showed that 5' adenosine monophosphate-activated protein kinase-mediated mitophagy was suppressed in DB mice post-IR. Pharmacological activation of 5' adenosine monophosphate-activated protein kinase by its agonist effectively restored mitophagy activation, leading to decreased mitochondrial oxidative stress and attenuated liver IR injury in DB mice., Conclusions: Our findings showed that diabetes increased oxidative stress to exacerbate liver IR injury by impairing 5' adenosine monophosphate-activated protein kinase-mediated mitophagy. Strategies targeting oxidative stress and mitophagy might provide a promising approach to ameliorate liver IR injury in diabetes patients., (© 2022 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To investigate the most effective weight ratio of Qiancao () and Haipiaoxiao () used to produce decoction for the treatment of abnormal uterine bleeding (AUB) in rats with incomplete abortion, and to study the possible mechanism., Methods: The models of AUB were established by incomplete drug abortion with mifepristone and misoprostol in pregnant rats. The therapeutic effects of decoctions made by eight different weight ratios of Qiancao () and Haipiaoxiao () were observed., Results: Statistical analysis revealed that the most effective weight ratio of Qiancao () and Haipiaoxiao () to treat AUB in this study was 2∶1., Conclusion: The insights gained from this study would improve understanding of the mechanisms involved in the effect of Qiancao () and Haipiaoxiao () on AUB.

Schedule exercise therapy (SET) is a novel nonpharmacological intervention for the treatment of chronic insomnia disorder (CID). The aim of this study was to explore the effects of SET on CID. Methods: One hundred and eighteen CID were recruited and randomized into medication (MED) or medication combined with SET (MSET) groups. Over 12 observational weeks, sleep and mood status were evaluated using the Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS), Self-rating Depression Scale (SDS), and Self-rating Anxiety Scale (SAS). At the end of the observational period, the rates of clinically effective hypnotic use were calculated. At 12 weeks, the PSQI progressively decreased for all subjects combined (P < .001) as well as ISI (P < .001), ESS (P < .001), SDS (P < .001), and SAS (P < .001). The decreases in PSQI (P < .05), ISI (P < .05), SDS (P < .01), and SAS (P < .05) in the MSET group were significantly larger than those in the MED group, but not the same as those in the ESS group (P > .05). At the trial endpoint, the clinically effective rate was significantly higher (P < .05) and the hypnotic usage rate was lower (P < .05) in the MSET group than in the MED group. SET may be an effective treatment for insomnia in patients with CID., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Eggplant (Solanum melongena L.) is an economically important vegetable crop in subtropics and tropics. In March 2021, a serious disease on eggplant seedlings about 20 days after transplanting was found in Rong'an County (25°28' N; 109°53' E), Guangxi, China, with an incidence of diseased plants of 35%. The initial symptom was water-soaked spots on the leaves, followed by irregular black-brown spots that gradually expanded outward, causing leaf necrosis and defoliation. Even parts of eggplant seedlings died after lesions extended to the stem and the surface of the diseased tissues was covered with white to blue mold. Four diseased eggplants were randomly collected from different fields. Small pieces of the symptomatic tissues were surface sterilized and incubated on potato dextrose agar (PDA) at 28°C for 4 days. A total of 12 strains with similar morphological characteristics were isolated, and four representative strains (FW-01 to FW-04) were characterized. The colony was initially white, changing to yellow-green after 7 days. Phialides were lageniform or ampulliform, 2.9 to 9.75 μm × 1.36 to 4.3 μm (n=50). Conidia were green, ellipsoidal to oblong, smooth, 2.1 to 3.3 μm × 1.6 to 2.33 μm (n=50). Chlamydospores were not observed on PDA. These morphological characteristics are consistent with the description of the genus Trichoderma (Samuels et al. 2012). To confirm the identification, from mycelia of the four isolates and DNA was extracted using the Fungal Genomic DNA Extraction Kit (Bioer Technology [Hangzhou] Co., Ltd.). Three gene regions (ITS, tef1 and rpb2) were amplified (Sadfi-Zouaoui et al. 2009; Atanasova et al. 2010) and sequenced (GenBank Accessions: OL677389 to OL677392 for ITS, OL743178 to OL743181 for tef1 and OL743182 to OL743185 for rpb2). ITS sequences shared 100% identity with sequences of T. reesei (MW514156) and T. parareesei (HM466668), and tef1 and rpb2 sequences showed more than 99% similarity with sequences of T. parareesei (KM263190 and HM182962). The phylogenetic tree of the concatenated sequences showed that four isolates were clustered with T. parareesei. Therefore, the isolates were identified as T. parareesei. To satisfy Koch's postulates, the pathogenicity of four strains was tested on healthy eggplant seedlings planted in a sterile potting mix. Eggplants at four leaves stage were inoculated using conidial suspensions (with a concentration of 1 × 106 conidia/ml), with two leaves of each eggplant inoculated with each isolate and the test repeated three times. The control eggplants leaves were inoculated with sterile water. All plants were placed in a greenhouse at 22 ± 3°C and 85% relative humidity, with a photoperiod of 12 h. The water-soaked spots appeared 48 h after inoculation. All inoculated leaves showed symptoms 3 days post-inoculation. The diseased leaves became brittle and abcissed, while the control leaves remained symptomless. Only T. parareesei was successfully re-isolated from the lesions. Atanasova et al. (2010) found that T. parareesei inhibited the growth of Lepidium sativum seedlings under in vitro conditions (Atanasova et al. 2010). To our knowledge, this is the first report of T. parareesei causing eggplant seedling blight in China. The pathogen can cause substantial economic losses in eggplant production. Therefore, the identification of the pathogen is of great significance for the diagnosis and control of the disease. The results of this study deepen the understanding of the pathogenicity of Trichoderma.

Background: The incidence of toxic diffuse goiter (Graves' disease) is higher in adolescents and preschool-aged children, with an upward trend. The incidence at 6-13 years of age is approximately 11.0%, and the incidences in men and women are 7.8% and 14.3%, respectively., Aim: To explore the clinical effect of methimazole combined with selenium in the treatment of toxic diffuse goiter (Graves' disease) in children and its effect on serum anti-thyroglobulin antibody (TRAb) and anti-thyroid peroxidase antibody (TPOAb)., Methods: A total of 103 children with Graves' disease treated in our hospital from January 2018 to June 2021 were divided into a traditional group and a combined group (15-20 mg methimazole orally given to children) and a combined group (50 µg selenium added on the basis of traditional treatment) according to different treatment methods to explore the therapeutic effects of the two methods and to observe the changes in thyroid volume and serum TRAb, TPOAb, free thyroxine (FT4) and inflammatory factor levels before and after treatment. The time taken for FT4 to return to normal was compared between the two groups., Results: Treatment was significantly more effective in the combined group than in the traditional group ( P < 0.05). The thyroid volumes of the children in the two groups was measured before and after treatment. Thyroid volume decreased significantly after treatment in both groups, and the thyroid volume was significantly lower in the combined group than in the traditional group ( P < 0.05). The serum levels of interleukin-6 (IL-6), IL-8, TRAb, TPOAb and FT4 in the two groups were detected before and after treatment. The levels of IL-6, IL-8, TRAb, TPOAb and FT4 were significantly lower in the combined group than in the traditional group ( P < 0.05). Follow-up of the children in the two groups showed that compared with the traditional group, it took less time for children in the combined group to return to the normal level ( P < 0.05)., Conclusion: Methimazole combined with selenium can effectively treat Graves' disease in children, reduce the expression of TRAb, TPOAb, FT4 and inflammatory factors, and improve the curative effect. Thus, the combined treatment warrants further clinical research., Competing Interests: Conflict-of-interest statement: No conflict of interest., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) pandemic continues to escalate intensively worldwide. Massive studies on general populations with SARS-CoV-2 infection have revealed that pre-existing comorbidities were a major risk factor for the poor prognosis of COVID-19. Notably, 49-75% of COVID-19 patients had no comorbidities, but this cohort would also progress to severe COVID-19 or even death. However, risk factors contributing to disease progression and death in patients without chronic comorbidities are largely unknown; thus, specific clinical interventions for those patients are challenging., Methods: A multicenter, retrospective study based on 4806 COVID-19 patients without chronic comorbidities was performed to identify potential risk factors contributing to COVID-19 progression and death using LASSO and a stepwise logistic regression model., Results: Among 4806 patients without pre-existing comorbidities, the proportions with severe progression and mortality were 34.29% and 2.10%, respectively. The median age was 47.00 years [interquartile range, 36.00-56.00], and 2162 (44.99%) were men. Among 51 clinical parameters on admission, age ≥ 47, oxygen saturation < 95%, increased lactate dehydrogenase, neutrophil count, direct bilirubin, creatine phosphokinase, blood urea nitrogen levels, dyspnea, increased blood glucose and prothrombin time levels were associated with COVID-19 mortality in the entire cohort. Of the 3647 patients diagnosed with non-severe COVID-19 on admission, 489(13.41%) progressed to severe disease. The risk factors associated with COVID-19 progression from non-severe to severe illness were increased procalcitonin levels, SpO2 < 95%, age ≥ 47, increased LDH, activated partial thromboplastin time levels, decreased high-density lipoprotein cholesterol levels, dyspnea and increased D-dimer levels., Conclusions: COVID-19 patients without pre-existing chronic comorbidities have specific traits and disease patterns. COVID-19 accompanied by severe bacterial infections, as indicated by increased procalcitonin levels, was highly associated with disease progression from non-severe to severe. Aging, impaired respiratory function, coagulation dysfunction, tissue injury, and lipid metabolism dysregulation were also associated with disease progression. Once factors for multi-organ damage were elevated and glucose increased at admission, these findings indicated a higher risk for mortality. This study provides information that helps to predict COVID-19 prognosis specifically in patients without chronic comorbidities., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the effect of different endodontic sealers (epoxy resin-based and bioceramic-based) and the time of post-cementation on the bond strength of a fiber post cemented with resin cement., Methods: Forty human premolars were instrumented and divided into 4 groups. According to the type of sealer and the time of post-cementation: AH-IM (AH Plus, post-cemented immediately after root canal treatment), SP-IM (iRoot SP, post-cemented immediately after root canal treatment), AH-OW (AH Plus, post-cementation after one week), and SP-OW (iRoot SP, post-cementation after one week). In each group, the samples were submitted to push-out test, and failure mode was assessed. Levene's test, one-way ANOVA, and Kruskal-Wallis analysis were applied for statistical analysis (α = 5%)., Results: The highest mean push-out bond strength was obtained from the SP-IM group in the apical part (10.45 ± 5.15MPa), while the lowest was observed in samples from the AH-OW group in the middle part (2.63 ± 1.54 MPa). One-way ANOVA showed that within the same root region, the time of post-cementation had a negative influence on the bonding strength in the SP groups in the middle and apical portion (P<0.05), however, when comparing the effect of type of sealers on bonding strength between the OW groups or IM groups within the same root region, no significant difference was observed regardless of the post cementation time (P>0.05)., Conclusions: The bond strength of the fiber post was higher when the post was cemented immediately after root canal treatment when the bioceramic sealer was applied., Clinical Relevance: The correct choice of an endodontic sealer and the proper time of post-cementation may help to obtain the best quality of post-and-core restoration., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Ralstonia solanacearum is a plant-pathogenic bacterium causing plant bacterial wilt, and can be strongly inhibited by methyl gallate (MG). Our previous transcriptome sequencing of MG-treated R. solanacearum showed that the yceI gene AVT05&#95;RS03545 of Rs-T02 was up-regulated significantly under MG stress. In this study, a deletion mutant (named DM3545) and an over-expression strain (named OE3545) for yceI were constructed to confirm this hypothesis. No significant difference was observed among the growth of wild-type strain, DM3545 and OE3545 strains without MG treatment. Mutant DM3545 showed a lower growth ability than that of the wild type and OE3545 strains under MG treatment, non-optimal temperature, or 1% NaCl. The ability of DM3545 for rhizosphere colonization was lower than that of the wild-type and OE3545 strains. The DM3545 strain showed substantially reduced virulence toward tomato plants than its wild-type and OE3545 counterpart. Moreover, DM3545 was more sensitive to MG in plants than the wild-type and OE3545 strains. These results suggest that YceI is involved in the adaptability of R. solanacearum to the presence of MG and the effect of other tested abiotic stresses. This protein is also possibly engaged in the virulence potential of R. solanacearum .

Objective: To establish an experimental prostatitis animal model in Sprague-Dawley (SD) rats through induction by treatment of estrogen and androgen at different concentrations., Methods: Fifty-three male SD rats aged 3 to 4 months were used in the study, and the castration model of male rats was established by excision of bilateral testes. The rats were randomly assigned to a blank group, a castration group and treatment groups receiving estrogen and androgen at different concentrations after castration, with 4 rats in each group. Dihydrotestosterone (DHT) and estradiol (E) were administered daily by subcutaneous injection to the treatment groups. All the rats were sacrificed by way of cervical dislocation after 1 month and the serum DHT and E concentrations of the rats in each group were assessed with ELISA. Prostate specimens were collected and the relative weight of the prostate of each group of rats was calculated. After HE staining of the prostate tissue, we observed with optic microscope structural changes in the prostate tissue and the state of prostatic inflammation in each group. Immunohistochemical examination was done to assess the expression of three inflammatory factors, transforming growth factor-β1 (TGF-β1), interleukin (IL)-6 and IL-8, in rat prostate tissues., Results: The results of HE staining of rat prostate tissue showed that, compared with the blank group and castration group, the degree of inflammation increased significantly in the E0.05+DHT 0.5 mg/kg group and DHT0.15+E0.15 mg/kg group ( P <0.05). However, once the concentration of DHT exceeded 0.5 mg/kg, the degree of inflammation did not further aggravate. The results of immunohistochemical staining showed that when the concentration of exogenous E was constant, the expression of TGF-β1 and IL-8 increased significantly in the E0.05+DHT 0.15 mg/kg group, E0.05+DHT 0.5 mg/kg group and E0.05+DHT 1.5 mg/kg group compared with that of the blank group ( P <0.05). In the E0.05+DHT 0.15 mg/kg group and E0.05+DHT 0.5 mg/kg group, the expression of TGF-β1 and IL-8 increased significantly compared with that of the castration group ( P <0.05). Once the concentration of DHT reached 0.5 mg/kg, further increase in the concentration of DHT did not lead to any significant changes in the expression of TGF-β1 or IL-8. In addition, when the concentration of exogenous DHT remained unchanged, the expressions of TGF-β1, IL-6, and IL-8 increased significantly in the DHT0.15+E 0.05 mg/kg group and DHT0.15+E 0.5 mg/kg group, compared with that of the blank group and castration group ( P <0.05)., Conclusion: Castration combined with treatment of different concentrations of estrogen and androgen could successfully induce the prostatitis model in SD rats., (Copyright© by Editorial Board of Journal of Sichuan University (Medical Sciences).)

Substance-related and addictive disorders (SRADs) are characterized by compulsive drug use and recurrent relapse. The persistence of pathological drug-related memories indisputably contributes to a high propensity to relapse. Hence, strategies to disrupt reconsolidation of drug reward memory are currently being pursued as potential anti-relapse interventions. Sulfur dioxide (SO 2 ), acting as a potential gaseous molecule, endogenously derives from sulfur amino acid and can exert significant neural regulatory effects. However, the role of SO 2 in reconsolidation of drug memory has not been determined. In the present study, we used morphine- or cocaine-induced conditioned place preference (CPP) mouse models with retrieval to investigate the effects of exogenous SO 2 donor treatment on reconsolidation of drug reward memory. We found that administration of SO 2 donor immediately after the retrieval impaired the expression of morphine or cocaine CPP. Furthermore, the exogenous SO 2 donor treatment 6 h post-retrieval or in the absence of retrieval had no effect on drug reward memory and the expression of CPP. SO 2 itself did not produce aversive effects nor did it acutely block morphine CPP. Our results indicate that exogenous SO 2 impairs reconsolidation of drug reward memory rather than inhibits the expression of drug reward memory. As such, SO2 holds potential for the treatment and prevention of SRADs and should be studied further., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Michelia alba (common name: white champaca), native to Indonesia, is a preciously ornamental and medicinal plant in the west and southeast of China and widely distributed in Nanning, Guangxi, China (Hou et al. 2018). In May 2020, a foliar disease of M. alba was observed in Nanning (22°51' N; 108°17' E), Guangxi, China, present on ca. 20-30% of the leaves. The disease began to develop from the margins of leaves in most cases. The symptoms recorded were light yellow spots, which gradually developed into ellipsoidal to irregular brown spots, surrounded by a wide yellow halo. The spots gradually enlarged in size and became grey-brown, with the dimension of 3.5 × 2.8 to 11.0 × 3.5 cm, even more than half of leaf area. In the later stage of infection, these spots coalesced resulting in necrosis and early shedding of the leaves. Sometimes black acervuli were observed on some lesions. For isolation of the fungus, ten symptomatic leaves were randomly sampled from five trees and washed with sterile water. Small pieces of infected tissue (about 4 mm2) were surface disinfected in 75% alcohol for 30 s and in 0.1% aqueous solution of mercury chloride for 1 min. Finally these tissue pieces were rinsed three times with sterile water, plated on potato dextrose agar (PDA) and then incubated for 7 days at 28℃ with a photoperiod of 12 h. Fifteen strains with similar morphological characterizations were isolated, and five representative isolates (BL-1 to BL-5) were purified. These cultures gave rise to grey-white colonies with bright orange conidial masses with contained one-celled, hyaline, guttulate conidia, measuring 12.68-20.70 × 4.27-7.84 µm (average 15.36 × 5.35 µm, n=100). Appressoria formed from conidia were brown, ellipsoidal or inverted trapezoid and measured 6.36-12.13 × 5.07-7.39 µm (average 8.29 × 6.36 µm, n=30). These morphological characteristics were similar to those of the Colletotrichum gloeosporioides species complex (Weir et al. 2012). To confirm identification, genomic DNA from mycelium of these five isolates was extracted, and the sequence of internal transcribed spacer (ITS), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), actin (ACT), calmodulin (CAL) and β-tubulin (TUB2) were amplified (Zhang et al. 2020), and the GenBank accession numbers for the sequences were MW186173 to MW186177 (ITS), MW161290 to 161294 (CHS-1), MW161295 to MW161299 (GAPDH), MW161285 to 161289 (ACT), MW084710 to 084714 (CAL) and MW161300 to MW161304 (TUB2). The phylogenetic tree of six combined genes of the five isolates clustered with Colletotrichum siamense strains (CBS 125378, ICMP 17795 and ICMP 18121). Therefore, the isolates were identified as C. siamense. Five isolates (BL-1 to BL-5) were tested for pathogenicity. Wounded and unwounded detached healthy leaves were inoculated using mycelial discs (5 mm in diameter) and conidial suspensions (with the concentration of 1 × 105 conidia/ml) at the same time, incubated in a growth chamber at 25-30℃ (85-90% relative humidity, with a photoperiod of 12 h). Three leaves (wounded left half blade and unwounded right half blade) were inoculated with different methods for each isolate, and the tests were repeated three times. Four days after inoculation, leaf spots were observed on all wounded leaves, while 5-10% of the unwounded leaves showed lesions. Control leaves inoculated with PDA discs and sterile water remained symptomless. Colletotrichum. siamense was re-isolated from the lesions, confirming Koch's postulates. At least 60 plant species have been reported to be infected by C. siamense worldwide (Ji et al. 2019). To our knowledge, this is the first report of C. siamense causing leaf spot on M. alba in China.

Bactrian camel as endemic economic species to the Northwest of China, its seasonal reproduction severely limits litter rates. In addition to melatonin, seasonal reproduction of animals is also regulated by the biological clock, but the specific molecular mechanism is not clear. To investigate the effects of melatonin and Cryptochrome (Cry) genes on seasonal reproduction, they were placed in ovarian granulosa cells, and their effects on reproduction were determined by measuring the concentrations of estradiol. Immunohistochemistry revealed that melatonin receptor protein (MT) was expressed in the cytosol and membrane of the ovarian granulosa cells, and the highest levels of CRY were expressed in the nuclei. The concentrations of estradiol in the cell culture supernatant were increased after the addition of exogenous melatonin or overexpression of MT, but these were decreased after MT was over expressed, and exogenous melatonin was added to the cells. In addition, there was a significant increase in the concentrations of estradiol after the Cry genes were overexpressed; however, the estradiol concentrations were decreased after the Cry genes were silenced. Our findings demonstrate that the MT and Cry genes play important roles in ovarian granulosa cell production of estradiol in a seasonally breeding species., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The piped hydraulic transportation of tube-contained raw material is a new low-carbon and environmental protection technique for transporting materials. The velocity characteristics of the spiral flow in the pipe with different numbers of guide bars installed on the surface of the piped vehicle body during piped hydraulic transportation of tube-contained raw material were studied by the theoretical analysis and model test. In the test, the numbers of guide bars placed on the surface of the piped vehicle body was respectively 3, 4, 5, and 6, and the studied sections were the section of the piped vehicle body and its rear section, and the flow discharge was 40 m 3 /h. The results showed that as the number of guide bars increased, the axial velocity of the section of the piped vehicle body increased gradually, while the axial velocity of the rear section of the piped vehicle reduced first and then increased. The section circumferential and radial flow velocity of the piped vehicle body and its rear section both increased first and then reduced. When the number of guide bars installed on the surface of the piped vehicle body was 4, the section circumferential flow velocity of the piped vehicle body and its rear section reached the maximum value, and their distributions were relatively uniform. The results offer theoretical basis so that we can optimize the structure of the piped vehicle and further popularize the piped hydraulic transportation technique of tube-contained raw material.

Crassocephalum crepidioides (Benth.) S. Moore, native to tropical Africa, is an important invasive weed in many countries, seriously threatening the safety of agricultural ecosystem. During December 2018, 100% of C. crepidioides plants exhibited leaf spots in the Kudzu (Pueraria lobata) garden in Tianlin County, Baise City, Guangxi, China (24°40'20.42″N, 106°11'33.51″E), but Kudzu was not affected by this disease. The leaf spots appeared as small brown spots surrounded by a yellow-green halo initially, enlarged to subrotund or irregular in shape, slightly sunken, then developed as a dark brown to dark spot with grey-white necrotic center (Supplementary Fig. 1 a,b), and exuded an orange droplet under high humidity conditions (Supplementary Fig. 1 c). Symptomatic leaf tissues were cut into small pieces (5 x 5 mm) from the junction of necrotic and healthy tissues, and small pieces were disinfected in 75% ethanol solution for 30 s and 0.1% mercury dichloride for 30 sec, then rinsed with sterile water 3 times. These tissues were plated onto potato dextrose agar (PDA) medium and incubated in a thermostatic incubator at 28°C under natural sunlight conditions. Four isolates with similar morphological features were obtained after purification. Colonies of these isolates exhibited creme-orange margins and aerial mycelium was sparse. The colonies formed concentric circles on the surface that were fusco-black, violet-slate and vinaceus-grey (from centre to edge), fusco-black on the reverse after 7 days (Supplementary Fig. 2 a,b), and then the pycnidia and conidia produced for about 30 days (Supplementary Fig. 2 c). Pycnidia of representative isolate YTH-12 were black, subglobose, and unilocular, 95.60-168.27 μm (average 128.32 µm) (n = 40) in diameter. The ostiole was single and central, slightly papillate to papillate and occasionally rostrate (Supplementary Fig. 2 d). Conidia were hyaline, oval to elliptical, aseptate, 2.30 to 5.83 × 1.42 to 3.50 µm (average, 4.36 × 2.03 µm) (n = 50) (Supplementary Fig. 2 e). These morphological characters are consistent with those described for Stagonosporopsis vannaccii (Crous et al. 2019). To further identify the isolate YTH-12, the rDNA internal transcribed spacer (ITS) region, 28s large subunit ribosomal RNA (LSU), RNA polymerase II second largest subunit (RPB2) gene and β-tubulin (TUB2) gene were amplified by polymerase chain reaction using the primer pairs ITS1/ITS4 (White et al. 1990), LR0R (Rehner and Samuels 1994)/LR7 (Vilgalys and Hester 1990), Btub2Fd/Btub4Rd (Woudenberg et al. 2009) and RPB2-5F2 (Sung et al. 2007)/fRPB2-7cR (Liu et al. 1999), respectively. The PCR products were purified and sequenced by Sangon Biotech Co. Ltd. (Shanghai, China). The sequences were deposited in GenBank (accession nos. MN892355, MN893911, MN905510 and MN905511). The ITS (522 bp), LSU (1313 bp), TUB2 (380 bp) and RPB2 (1193 bp) nucleotide sequences showed 100% identity to S. vannaccii strain LFNO148 (accession nos. MK519453, MK519452, MK519454 and MN534891). Phylogenetic analysis based on the multi-locus sequences of ITS, LSU, RPB2 and TUB2 was performed in MEGA version 6.0 (Chen et al. 2015). The relative stability of the branches was evaluated by bootstrapping with 1000 replications. The isolate YTH-12 was placed in the same clade as S. vannaccii with 100% bootstrap support. Based on morphology and molecular analyses, this pathogen was identified as S. vannaccii. To satisfy Koch's postulates, the isolate YTH-12 was inoculated on leaves of C. crepidioides plants. Twenty punctured leaves and twenty unwounded leaves were inoculated with a 5-mm-diameter mycelial disc, respectively. Leaves inoculated with sterile PDA discs were used as blank controls. Plants were maintained in a growth chamber (25°C-28°C and relative humidity 80%-90%). Brown spots were observed on inoculated leaves (both punctured and unwounded) about 30 hours after inoculation and typical symptoms appeared about 55 hours after inoculation (Supplementary Fig. 1 d), and the diseased leaves produced black pycnidia and orange droplet 10 days after inoculation (Supplementary Fig. 1 e). All inoculated leaves developed symptoms similar to those on the naturally infected plants in the garden and the disease incidence reached 100%, whereas the control leaves remained symptomless (Supplementary Fig. 1 f). The same fungus was re-isolated from inoculated leaves. To our knowledge, this is the first report of S. vannaccii causing leaf spot on C. crepidioides in China. So far, Stagonosporopsis vannaccii has been reported as a plant pathogenic fungus only in Brazil, causing anthracnose symptoms on pods of soybean (Crous et al. 2019). Crassocephalum crepidioides is a widely distributed weed. If S. vannaccii has strong host specificity, it is possible to be used as a biocontrol fungus to control the weed. Conversely, if the fungus has a wider host range, C. crepidioides may act as a good bridge to spread the pathogen. This study helps to deepen the understanding of S. vannaccii and its associated plant diseases.

Berberine, a botanical drug, has great ability to inhibit the growth of Xanthomonas oryzae pv. oryzae . However, the antibacterial mechanism of berberine against X. oryzae pv. oryzae remains poorly understood. In this study, we investigated the physiological and transcriptional response of X. oryzae pv. oryzae to berberine. When strain X. oryzae pv. oryzae GX13 was treated with berberine (10 µg/ml), the hypersensitive response in tobacco, virulence to rice, pathogen population in the rice xylem, production of extracellular polysaccharide (EPS), and activity of extracellular hydrolases decreased, but the levels of pyruvate and ATP increased. Moreover, biofilm formation was inhibited, and the cell membrane was damaged. Transcriptome sequencing analysis showed downregulated expression of gspD , gspE , and gspF , involved in the type II secretion system (T2SS); hrcC , hrcJ , hrcN , and others, involved in the type III secretion system (T3SS); gumB and gumC , associated with EPS; zapE , ftsQ , and zapA , associated with cell division; lpxH , lpxK , kdtA , and others, associated with the membrane; and pyk , pgk , and mdh , encoding pyruvate kinase, phosphoglycerate kinase, and malate dehydrogenase, respectively. Upregulated expression was observed for nuoA , nuoB , and nuoH , encoding the NADH dehydrogenase complex, and atpF , atpC , and atpB , encoding ATP synthase. An adenylate cyclase ( CyaA ) fusion assay showed that berberine affects type three effector protein secretion via the T3SS and reduces effector translocation in X. oryzae pv. oryzae . It is speculated that the negative growth and virulence phenotypes of berberine-treated X. oryzae pv. oryzae GX13 may involve differentially expressed genes associated with cytoarchitecture and energy metabolism, and these effects on primary cell function may further dampen virulence and result in differential expression of T3SS- and T2SS-related genes.

Although typically arranged in solid alveolar fashion, chromophobe renal cell carcinoma (RCC) may also show several other architectural growth patterns. We include in this series 8 chromophobe RCC cases with prominent papillary growth, a pattern very rarely reported or only mentioned as a feature of chromophobe RCC, which is lacking wider recognition The differential diagnosis of such cases significantly varies from the typical chromophobe RCC with its usual morphology, particularly its distinction from papillary RCC and other relevant and clinically important entities. Of 972 chromophobe RCCs in our files, we identified 8 chromophobe RCCs with papillary growth. We performed immunohistochemistry and array Comparative Genomic Hybridisation (aCGH) to investigate for possible chromosomal aberrations. Patients were 3 males and 5 females with age ranging from 30 to 84 years (mean 57.5, median 60 years). Tumor size was variable and ranged from 2 to 14 cm (mean 7.5, median 6.6 cm). Follow-up was available for 7 of 8 patients, ranging from 1 to 61 months (mean 20.1, median 12 months). Six patients were alive with no signs of aggressive behavior, and one died of the disease. Histologically, all cases were composed of dual cell population consisting of variable proportions of leaf-like cells with pale cytoplasm and eosinophilic cells. The extent of papillary component ranged from 15 to 100% of the tumor volume (mean 51%, median 50%). Sarcomatoid differentiation was identified only in the case with fatal outcome. Immunohistochemically, all tumors were positive for CK7, CD117 and Hale's Colloidal Iron. PAX8 was positive in 5 of 8 cases, TFE3 was focally positive 3 of 8 tumors, and Cathepsin K was focally positive in 2 of 8 tumors. All cases were negative for vimentin, AMACR and HMB45. Fumarate hydratase staining was retained in all tested cases. The proliferative activity was low (up to 1% in 7, up to 5% in one case). Three cases were successfully analyzed by aCGH and all showed a variable copy number variation profile with multiple chromosomal gains and losses. CONCLUSIONS: Chromophobe RCC demonstrating papillary architecture is an exceptionally rare carcinoma. The diagnosis can be challenging, although the cytologic features are consistent with the classic chromophobe RCC. Given the prognostic and therapeutic implications of accurately diagnosis other RCCs with papillary architecture (i.e., Xp11.2 translocation RCC, FH-deficient RCC), it is crucial to differentiate these cases from chromophobe RCC with papillary architecture. Based on this limited series, the presence of papillary architecture does not appear to have negative prognostic impact. However, its wider recognition may allow in depth studies on additional examples of this rare morphologic variant., Competing Interests: Declaration of competing interest All authors declare no conflict of interest., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Individualized therapy involves genetic test of drug metabolism, which provides information about the initial dose and therapeutic drug monitoring for adjusting the subsequent dose. Consequently, toxic side effects are expected to be minimized and therapeutic effects to be maximized. In this study, an ultra-performance liquid chromatography tandem mass spectrometry method that was specific, accurate and sensitive was developed to simultaneously determine azathioprine two metabolites, 6-thioguanine nucleotides (6-TGN) and 6-methyl-mercaptopurine riboside (6-MMPr) in the whole blood lysate. We precipitated the sample by trifluoroacetic acid under the protection of dithiothreitol, with 6-MMPr and 6-TGN being hydrolyzed to produce 6-methymercaptopurine and 6-thioguanine. In the chromatographic separation, Waters ACQUITY BEH C18 (2.1 × 100 mm, 1.7 μm) chromatographic column was applied and gradient elution was conducted with 0.02 mol/L ammonium acetate buffer (which contains 0.3% formic acid) and acetonitrile at a flow rate of 0.4 ml/min. Tandem mass spectrometry in multiple reaction monitoring mode was applied for detection via electrospray ionization source in positive ionization mode. The analyzing process lasted for no more than 2 min. The calibration curve for each metabolite fitted a least squares model (weighed 1/X) from 1.25 to 5000 ng/ml (r 2  > 0.99). The ion pairs were detected as 6-MMP m/z 167.07 → 152.15, 6-TG m/z 168.06 → 134.13, and internal standard m/z 171.07 → 137.14. Under the guidance of FDA guidelines for bioanalytical method validation, we carried out validation and obtained satisfactory results. The method was successfully utilized for monitoring the concentrations of each metabolite from 65 affected patients who had received azathioprine maintenance therapy and achieved optimal results., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Bone is one of the most important organs in the human body. It provides structure, function, and protection for other vital organs; therefore, bone maintenance and homeostasis are critical processes. As humans age, their bone mineral density decreases, which leads to diseases like osteoporosis. This disease affects one in two women and one in five men aged 50 and over. As the aging population increases, the interest and significance of studying this debilitating bone disease becomes more relevant. Current therapeutic products for osteoporosis have many side effects and can be taken for a limited number of years. Most therapeutic products only focus on decreasing bone resorption, not increasing bone formation. Bone morphogenetic protein 2 is an essential growth factor that drives osteoblast differentiation and activity and is essential for bone formation. However, usage in the clinic is unsuccessful due to several side effects. Recently, a signaling disparity in bone marrow stromal cells within the bone morphogenetic protein pathway that led to decreased bone morphogenetic protein 2 responsiveness was identified in patients diagnosed with osteoporosis. However, it is unclear how other cell populations, especially osteoblasts, which are key players in bone remodeling, are affected and whether the bone morphogenetic protein pathway is affected during osteoporosis. Our research group designed a novel peptide, casein kinase 2.3, that acts downstream of the bone morphogenetic receptor type Ia and increases bone mineralization in murine cells and primary bovine osteoblasts. The aim of the study presented here was to compare the responsiveness of osteoblasts to bone morphogenetic protein 2 and casein kinase 2.3, especially in patients diagnosed with osteoporosis. Mature osteoblasts were extracted from patients diagnosed with osteoporosis or osteoarthritis from Christiana Care Hospital in Newark, Delaware. They were stimulated with either bone morphogenetic protein 2 or casein kinase 2.3, and their effect on osteoblast activity was determined. The osteoporotic patients showed no mineralization response to bone morphogenetic protein 2 stimulation, while the osteoarthritis patients significantly responded to bone morphogenetic protein 2 stimulation. Furthermore, markers for osteoblast activity were increased by casein kinase 2.3, which was in sharp contrast to bone morphogenetic protein 2. This further supports a major bone morphogenetic protein signaling disparity in both the elderly and those suffering with osteoporosis. Both patient types did significantly respond to casein kinase 2.3. Further analysis of the bone morphogenetic protein pathway could lead to new therapeutic products for osteoporosis.

Background: The objective of this study was to explore the influence factors of hospitalization costs of treating colorectal cancer in China. And the study provides new estimates on hospitalization costs and length of hospital stay for patients with colorectal cancer in China., Methods: Data for inpatient hospitalization associated with colorectal cancer were obtained from a 3-tier hospital in Guangdong Province and were analyzed post hoc. We conducted descriptive statistical methods, Wilcoxon rank-sum tests (for 2 groups) and the Kruskal-Wallis test (for more than 2 groups) to analyze the hospitalization costs of treating colorectal cancer., Results: The analysis included 8021 patients (female: 40.54%; mean age; 61.80 ± 13.28 years; male: 59.46%; mean age: 61.80 ± 13.28 years). The overall mean length of hospital stay was 11.35 days. Over the 5 years, the mean length of hospital stay showed a small decrease from 12.22 days in 2012 to 10.69 days in 2016, while per-day costs showed a trend of increase between 2012 and 2015 (increase from < 1190.94 to < 1382.50). The mean length of hospital stay was statistically significant difference was found for sexes (P = .039) and insurance status (P < .001). The mean hospitalization costs were < 16,279.58. Mean hospitalization costs were different among the UEBMI, the URBMI and the Unspecified (< 17,114.58, < 15,555.05, and < 17,735.30, respectively; P < .001)., Conclusion: The study showed that hospitalization costs increase were associated with a small decreasing length of hospital stay and increasing per-day hospitalization costs. Moreover, the proportion of the hospitalization costs reimbursed by insurances increased. For inpatients with UEBMI, it possibly lead to over treatment and the medical expense rise which result in medical resources waste and significant society costs. The rising hospitalization costs may lead to a remarkably increased financial burden in the future in China.

Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.

The aim of this study was to investigate the correlation between CYP2C19 genotype and dose-adjusted voriconazole (VCZ) trough concentrations (C0/dose).We analyzed the correlation between CYP2C192(681G>A), CYP2C193(636G>A), and CYP2C1917(-806C>T) genetic polymorphisms and the dose-corrected pre-dose concentration (C0/dose) in 106 South-western Chinese Han patients.The frequencies of variant alleles of CYP2C192, 3, and 17 were 29.7%, 4.25%, and 0.92%. For 49.3% of the VCZ samples, the therapeutic window between 1.5 and 5.5 μg/ml was reached. Following the first dose VCZ measurement, in subsequent samples the proportion of VCZ C0 within the therapeutic window increased, suggesting effective therapeutic drug monitoring (TDM) (P = .001). The VCZ C0 was significantly different (P = .010) between patients with normal metabolism (NMs), intermediate metabolism (IMs), and poor metabolism (PMs). The VZC C0/dose was 12.2 (interquartile range (IQR), 8.33-18.2 μg·ml/kg·day), and 7.68 (IQR, 4.07-16.3 μg·ml/kg·day) in PMs and IMs patients, respectively, which was significantly higher than in NMs phenotype patients (4.68; IQR, 2.51-8.87 μg·ml/kg·day, P = .008 and P = .014).This study demonstrated that the VCZ C0/dose was significantly influenced by the CYP2C19 genotype in South-western Chinese Han patients. In this patient population, more over-exposure was observed in patients with a CYP2C19 genotype associated with poor or intermediate metabolism. CYP2C19 genotype-based dosing combined with TDM will support individualization of VCZ dosing, and potentially will minimize toxicity and maximize therapeutic efficacy.

Background: To investigate the epidemiological features of breast cancer laterality and molecular subtypes in southern China., Materials and Methods: A total of 2,049 cases who were diagnosed with unilateral breast cancer in the past 5 years were classified based on laterality and molecular subtypes. Molecular subtypes were defined in accordance with the 2013 St. Gallen recommendations., Results: Breast cancer was more likely to be diagnosed in the left breast than in the right at a rate of around 5%. In the case of invasive carcinomas, the right breast was more commonly affected than the left in young (<40 years old) patients (left-to-right [L:R] ratio 0.80, 95% CI 0.65, 0.98), whereas the opposite trend was found in old (≥40 years old) patients (L:R ratio 1.06, 95% CI 1.02, 1.73). Except for invasive mucinous and invasive medullary breast cancers, the other histological types occurred more frequently on the left side than on the right. In situ cancer with a defined subtype was likely to be diagnosed as luminal B(HER-2+). Except for invasive medullary and invasive nonspecific cancers, other invasive carcinomas with a defined subtype were most likely to be diagnosed as luminal B(HER-2-). The age of ≥40 years was a risk factor for luminal B(HER-2+), and a significant correlation was present between the right breast and luminal B(HER-2+)., Conclusion: We explored the risk factors of breast cancer laterality and various molecular subtypes and found that age may be a predictor of breast cancer laterality. We found that age and laterality are the probable risk factors of the luminal B(HER-2+) type of breast cancer. These results provide a basis for the epidemiological characterization of breast cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: The poor prognosis of colorectal cancer (CRC) largely results from local invasion and tumor metastases. Epithelial-mesenchymal transition (EMT) is a key step in the progression of solid tumors and plays a vital role in tumor metastasis. Recent studies demonstrate that C-X-C motif chemokine 11 (CXCL11) is involved in various cancers' progression. However, its biological activity in CRC needs deeper exploration., Methods: The level of CXCL11 in CRC tissues and cell lines was determined using the quantitative real-time PCR (qRT-PCR) assay. The MTT, colony formation, wound healing and Transwell invasion assays were applied to assess the role of CXCL11 in CRC cell growth, migration and invasion, in vitro, respectively. A xenograft model was constructed to analyze the function of CXCL11 in CRC cell growth in vivo., Results: CXCL11 was over-expressed in CRC tissues and cell lines. Repression of CXCL11 significantly inhibited CRC cell migration, invasion and EMT in vitro. In addition, down-regulation of CXCL11 reduced CRC cell growth and metastasis in vivo. Finally, we revealed that repression of CXCL11 inhibited the metastatic ability of CRC cell in a N-cadherin dependent manner., Conclusion: In summary, this study explicates the oncogenic activities of CXCL11 in CRC cell growth and metastasis., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Introduction: Dynamin 3 (DNM3) is a large GTPase that possesses mechanochemical properties and has been shown to be involved in malignancies. However, most studies about DNM3 are observational, and knowledge of the precise molecular mechanism of DNM3 remains limited., Materials and Methods: We constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, which was then transfected into SW620 and LoVo cells. One cell line was divided into three groups. DNM3 mRNA and protein expression was analyzed by quantitative real-time PCR and Western blot assay. To investigate DNM3 biological activity in colon cancer SW620 and LoVo cell line, we performed cell proliferation, transwell migration, and invasion assay. Matrix metalloproteinase (MMP)-2 and MMP-9 protein expressions were detected by Western blot., Result: We successfully constructed a PCDH-CMV-MCS-EF1a-GFP-Puro-DNM3 recombinant eukaryotic expression vector, and stable DNM3 expression was observed in SW620 and LoVo cell lines. The vector overexpressing DNM3 inhibited the proliferation, weak invasion, and migration ability of colon cancer SW620 and LoVo cells relative to those in the control group (all P <0.001). DNM3 downregulated the protein expression of MMP-2 and MMP-9., Conclusion: DNM3 may weaken the malignant behavior of colon cancer and may have promoted the invasion and migration of colon cancer by regulating the expression of MMP-2 and MMP-9., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Objective: To evaluate the effect of an automatic identification system of Schistosoma japonicum miracidia, and compare it with the traditional eye detection method in the simulation field., Methods: A total of 260 fecal samples were collected from schistosomiasis non-endemic areas, and the test sample bottles containing schistosome miracidia were prepared according to different experimental needs. Thirty fecal samples for the sensitivity test were separately added with five fresh miracidia per sample, and then the mixed samples were detected by two experienced technicians (with more than 15 years' traditional test experience) or the automatic system. The positive detection rates were compared between the two methods. Thirty fecal samples for repetition test were separately added with ten fresh miracidia per sample, and then the mixed samples were detected separately with the automatic identification system by two experienced technicians. The results were compared between two persons. The two methods including the automatic identification system and the traditional eye detection method were carried out blindly with totally 200 samples in the simulation field. There were three groups (each with 30 samples) : Group 1 with more than 21 fresh miracidia, Group 2 with 6 to 20 fresh miracidia, and Group 3 with 1 to 5 fresh miracidia. The other 110 samples were as a negative group. The detection time, accuracy, missed detection rate, and false detection rate of the two methods were statistically compared., Results: The positive detection rates of the 30 positive samples were 43.33% and 33.33% by the two technicians with the traditional eye detection method, respectively, while the detection rate was 80.00% by the automatic identification system, and the difference was statistically significant ( χ 2 = 7.05, χ 2 = 12.97, both P < 0.01). Thirty positive samples were detected by the two technicians using the same automatic identification system, and the positive detection rates of the two were 96.67% and 86.67%, respectively, with no significant difference ( χ 2 = 0.27, P > 0.05). The experiments showed that the correct detection rate of the positive samples was 98.00% by the automatic identification system, which was higher than 79.75% by the traditional eye detection method. The detection time of the automatic identification system was shortened by half compared with that of the traditional eye detection method. The missed detection rate, and false detection rate of the automatic identification system were 2.22% and 1.82%, respectively, which were much lower than 35.56% and 7.73% of the traditional eye detection method., Conclusions: Compared with the traditional eye detection method, the automatic identification system of S. japonicum miracidia has the advantages of high sensitivity, good repeatability, short detection time, high accuracy, low missed detection rate, and low false detection rate. It can be used in the field and clinical detection in replacement of the traditional eye detection method.

BACKGROUND We investigated whether a low fixed Tac starting dose regimen could lead to a better achievement of Tac target concentrations, as well as an effective immunosuppressive treatment, in Chinese kidney transplant recipients (KTRs). MATERIAL AND METHODS We collected whole-blood and serum samples from 189 KTRs and the Tac starting dose was 2, 2.5, or 3 mg/day. Information on Tac C0, dose, body weight, body mass index (BMI), Scr, eGFR, and CYP3A5 genotypes were collected from a routine therapeutic drug monitoring database. The correlation between Tac C0 and body weight (or BMI) was investigated by calculating the goodness of fit. Multivariable logistic regression was performed to estimate the independent associated factors. RESULTS The patients with 3 mg per day of Tac had higher C0 at day 7 compared to those with 2 or 2.5 mg. For patients receiving the same Tac starting dose, no significant difference was found in Tac C0 at day 7 among different body weight or BMI groups. There was no significant difference in Scr or eGFR at 1 year after transplant, nor was there a significant difference in the rates of DGF or AR at post-transplant day 30 among different Tac starting dose groups or among the 3 Tac C0 range groups. CYP3A5 genotype and Tac initial dose were independently associated with Tac C0. CONCLUSIONS CYP3A5 genotype and Tac initial dose were independently associated with Tac C0 in renal transplant recipients. Our results suggest that a low Tac target C0 range (5-8 ng/ml) with a low fixed starting dose (3 mg/day) would be safe and effective among Chinese KTRs.

Strain 06168H-1 T was isolated from a fishpond sediment sample collected from the southern area of Taiwan, and a polyphasic approach was used to determine its taxonomic position. The isolate grew between 20-40 °C and 0-8 % (w/v) NaCl. It produced branched and unfragmented substrate mycelia. Short spore chains (3-10 spores per chain) formed on branched aerial mycelia. The spore chains contained non-motile, smooth-surfaced, oval spores. Galactose, arabinose and ribose were the whole-cell sugars and meso-diaminopimelic acid was present in its peptidoglycan. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, hydroxyphosphati dylethanolamine and a ninhydrin-positive phosphoglycolipid. The predominant menaquinone was MK-9(H4) and minor components were MK-8(H4) and MK-9(H6). Mycolic acids were not detected. The major cellular fatty acids were iso-C16 : 0 and C17 : 1ω6c and C17 : 0ω8c. The DNA G+C content of the strain was 70.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed this strain clustered with the members of the genus Saccharomonospora and was closely related to Saccharomonospora xinjiangensis, Saccharomonospora azurea and Saccharomonosporacyanea. The levels of similarity between this strain and the closely related species were: Sxinjiangensis BCRC16887 T , 98.34 %; S. azurea BCRC 16220 T , 98.27 %; and S. cyanea BCRC 16886 T , 97.99 %. Based on phylogenetic characteristics, strain 06168H-1 T represents a novel species of the genus Saccharomonospora. We thus propose the name Saccharomonospora piscinae sp. nov. for this novel strain, with strain 06168H-1 T (=BCRC 16893 T =KCTC 19743 T ) as the type strain.

Radiotherapy is a vital treatment option for patients with nasopharyngeal carcinoma (NPC). Concurrent cisplatin-based radiochemotherapy with or without adjuvant chemotherapy had acquired good clinical effects with good local control rates. However, a number of patients present with metastasis following systemic regimens or initial diagnosis of locally advanced NPC, which cause difficulty for subsequent therapy. Therefore, there is an urgent requirement to discover novel targeted therapies. The present report describes one case of a patient with NPC and multiple metastases. The patient was treated with systemic therapy in combination with bevacizumab, palliative radiotherapy and chemotherapy following treatment with cetuximab and concurrent chemoradiotherapy in 2015. Following the addition of bevacizumab, metastases were reduced or disappeared after >2 months, and the duration of progression-free survival was 7 months. Bevacizumab is a monoclonal antibody that targets VEGF, and it is associated with angiogenesis, which causes the growth, invasion and progression of tumors. In previous studies, bevacizumab has been approved for the treatment of several types of malignant cancer and it has been able to effectively improve prognosis. In the present review, the effect of adding bevacizumab to systemic therapy for the treatment of NPC was analyzed, with a particular focus on advanced and metastatic diseases. A growing number of phase I/II clinical trials involving bevacizumab for NPC have been conducted with clinical outcomes showing improved rates of overall survival and progression-free survival as well as improvements in the quality of life of patients. However, severe or deadly toxicities can also result from combination treatment with bevacizumab. In the future, bevacizumab may become a common addition to systemic therapy for the treatment of locally advanced and metastatic NPC.

Background: A molecular biomarker of physiologic age, as opposed to chronologic age, is needed in clinical medicine. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGsn) and 8-oxo-7, 8-dihydroguanosine (8-oxoGsn) are two promising aging biomarkers. Methods: A total of 1,228 healthy Chinese residents (613 males and 615 females) 2-90 years of age were randomly selected. Spot urine samples were collected, and the concentrations of 8-oxodGsn and 8-oxoGsn were measured using ultra-high-performance liquid chromatography with a triple quadrupole mass spectrometer (UPLC-MS/MS). Method validation, including accuracy, precision, linearity and quantification limit, was performed. The relationship between oxidized guanosine and age/gender was evaluated. Results: 8-oxodGsn and 8-oxoGsn were eluted at 1.61 and 1.30 min, respectively. The calibration curve was linear in the range of 0.2-500 ng/ml for both analytes. The lowest limit of quantification (LLOQ) was 0.2 ng/ml for 8-oxodGsn and 0.1 ng/ml for 8-oxoGsn. There was an age-dependent increase in the biomarkers from the 21- to 30-year-old group to the 81- to 90-year-old group in both genders. In the subjects older than 61 years of age, the levels of 8-oxodGsn as well as 8-oxoGsn in urine were much higher in females than in males. The content of 8-oxoGsn correlated more closely with age and was higher (approximately 2-fold) than that of 8-oxodGsn for a given individual. Conclusions: 8-oxodGsn and 8-oxoGsn can be easily measured by UPLC-MS/MS. Urinary 8-oxoGsn may be a potential biomarker to determine a person's physiologic age and identify individuals at high risk of developing age-associated disease.

Objective: To develop a dynamic automatic identification system (device) of Schistosoma japonicum miracidia to achieve the automatic detection and improve the detection rate and efficiency of schistosome miracidia., Methods: The dynamic automatic identification system (device) of S.japonicum miracidia was composed of an optical stereoscope, a digital camera, dynamic automatic tracking recognition software, and a computer. Under different conditions, the detection rates and efficiency of the system were compared with those of five professional persons., Results: The basic function of the system was to identify, label and warn the miracidia of S. japonicum , and the records could be saved automatically. The laboratory tests showed that the missing rate of the system was 0. The total consistent rates of the manual detection were 74.67% and 66.67% in the condition with and without water bug, while the total consistent rates of the system were 100.00% and 96.67%, respectively ( χ 2 = 9.634, 11.081, both P < 0.01) ., Conclusions: The system is much superior to manual detection in the accuracy and speed, and the system could completely replace the manual detection. Therefore, the system could be used in the field and basic research of schistosomiasis.

Background: T cell immunoglobulin mucin-3 (Tim-3) has been reported to participate in the regulation of immune response and the induction of allograft tolerance. However, the association between Tim-3 and renal allograft dysfunction is unclear. We studied the expression of cellular and soluble Tim-3 (sTim-3), soluble galectin-9 (sGal-9) and carcinoembryonic antigen-related cell adhesion molecule-1 (sCEACAM-1) in kidney transplantation recipients (KTRs) to explore their roles in allograft dysfunction., Methods: 96 KTRs (53 with stable graft and 43 with graft dysfunction) and 30 healthy controls (HC) were enrolled. Among the KTRs, 55 used Tacrolimus (TAC) and 41 used Sirolimus (SRL). In the dysfunction group, 29 recipients have undergone graft biopsy and 14 were classified as biopsy-proven rejection (BPR). Cellular Tim-3 was determined by flow cytometry. sTim-3 was determined by ELISA. sGal-9 and sCEACAM-1 were determined by Bio-Plex® suspension array system., Results: KTRs with renal dysfunction showed significantly higher levels of sTim-3 and sGal-9 but similar levels of cellular Tim-3 and sCEACAM-1 compared with stable recipients. Correlation analysis revealed that estimated glomerular filtration rate (eGFR) was negatively associated with sTim-3 and sGal-9. Both BPR and non-BPR groups showed comparable levels of Tim-3, Gal-9 and CEACAM-1. Moreover, SRL group showed significantly higher levels of sCEACAM-1 than TAC and HC groups., Conclusions: sTim-3 and sGal-9 were promising biomarkers for allograft dysfunction, but unable to differentiate allograft rejection from other causes of renal dysfunction in KTRs. Moreover, long-term administration of sirolimus would up-regulate sCEACAM-1 level, while exert similar regulatory effects on Tim-3 and Gal-9 compared to tacrolimus., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Egl-9 family hypoxia-inducible factor (HIF)3/prolyl hydroxylase 3 (EGLN3/PHD3) serves a role in the progression and prognosis of cancer. PHD3 is able to induce apoptosis in HepG2 cells. In the present study, the protein levels of PHD3 and HIF2α were analyzed by western blot analysis and immunohistochemistry in 84 paired hepatocellular carcinoma (HCC) tissues and adjacent non-tumor liver tissues. The mRNA levels of PHD3 and HIF2α were analyzed by reverse transcription-quantitative polymerase chain reaction. PHD3 was overexpressed in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.003; immunohistochemistry positive rate: P=0.001). The high level of expression of PHD3 in HCC tissues was associated with good differentiation (mRNA expression: P=0.002; protein expression: P<0.001) and small tumor size (mRNA expression: P<0.001; protein expression: P=0.002). In addition, HIF2α expression was lower in HCC tissues compared with adjacent liver tissues (mRNA expression: P<0.001; protein expression: P=0.002; immunohistochemistry positive rate: P=0.002). No statistically significant associations were identified between HIF2α expression and clinicopathological characteristics. Pearson's and Spearman's correlation coefficients revealed no correlation between HIF2α and PHD3 expression in HCC. In conclusion, PHD3 expression acts as a favorable prognostic marker for patients with HCC. There is no correlation between PHD3 and HIF2α expression in HCC.

Aim: To evaluate the associations between development of retinopathy of prematurity (ROP) and serum lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR)., Methods: A retrospective cohort study was performed, involving infants who were screened for ROP from January 2015 to December 2015. Preterm newborns of ≤32 gestational weeks with ROP were enrolled as the observation group, and non-ROP infants were enrolled as the control group, whose complete blood cell were measured within the first 24h of life. The levels of NLR, LMR and PLR were determined in all groups. The data obtained were analyzed using univariate and multivariate logistic regression analysis., Results: In this study, 40 cases of ROP were enrolled and 40 cases of non-ROP as controls. The LMR levels were significantly higher ( P <0.001) in ROP group (3.96±1.16) compared to non-ROP group (2.85±0.79). The NLR levels were significantly lower ( P =0.035) in ROP group {median [interquartile range (IQR)], 0.88 (0.67-1.46)} compared to non-ROP group [median (IQR), 1.20 (0.85-1.89)]. The median PLR values were 61.99 (IQR, 50.23-75.98) in ROP group and 69.24 (IQR, 55.52-88.12) in non-ROP group ( P =0.104). Logistic regression analysis suggested that LMR was an independent risk factor for ROP (OR: 0.275; 95% CI: 0.134-0.564; P =0.001)., Conclusion: The findings demonstrate that higher LMR is independently and significantly associated with the development of ROP, and the LMR may be invoked as a predictive tool for identifying risk for ROP.

This paper describes an integrated multichannel neural recording analog front end (AFE) with a novel area-efficient driven right leg (DRL) circuit to improve the system common mode rejection ratio (CMRR). The proposed AFE consists of an AC-coupled low-noise programmable-gain amplifier, an area-efficient DRL block and a 10-bit SAR ADC. Compared to conventional DRL circuit, the proposed capacitor-less DRL design achieves 90% chip area reduction with enhanced CMRR performance, making it ideal for multichannel biomedical recording applications. The AFE circuit has been designed in a standard 0.18-μm CMOS process. Post-layout simulation results show that the AFE provides two gain settings of 54dB/60dB while consuming 1 μA per channel under a supply voltage of 1 V. The input-referred noise of the AFE integrated from 1 Hz to 10k Hz is only 4 μVrms and the CMRR is 110 dB.

The transitional period from hospital to home is critical to decreasing rates of preventable, poor post-discharge outcomes. Older adults with chronic heart failure (CHF) may be challenged to exercise during the transitional period. The purpose of the current study was to test the effects of low-intensity exercise on health-related quality of life (HRQoL), physical function, and heart function in Chinese older adults with CHF during the transitional period. The study was randomized, single-blinded, and controlled. Seventy-eight older adults with stable CHF were evaluated. The intervention group (n = 41) participated in a regular low-intensity walking protocol and the control group (n = 38) did not. Measures included the Minnesota Living with Heart Failure Questionnaire (MLHFQ), 6-minute walk distance (6MWD), Timed Up and Go (TUG) test, resting heart rate (RHR), and left ventricular ejection fraction (LVEF). After 12 weeks, the intervention group showed significant improvements in MLHFQ, 6MWD, and TUG scores compared to the control group (p < 0.05), and no significant improvements in RHR and LVEF (p > 0.05). Low-intensity exercise during the transitional period is an effective way to improve HRQoL and physical function in older adults. [Res Gerontol Nurs. 2017; 10(3):121-128.]., (Copyright 2017, SLACK Incorporated.)

Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder characterized by a mismatch between acetabulum and femoral head. Mechanical force plays an important role during the occurrence and development of abnormities in acetabulum and femoral head. In this study, we established a mechanical force model named cyclic compressive stress (Ccs). To analyze the effect of Ccs on DDH, we detected special genes in chondrocytes and osteoblasts. Results showed that Ccs downregulated chondrogenesis of ADTC5 in a concentration-dependent manner. Moreover, the mRNA level of Scinderin (Scin) considerably increased. We established lentivirus-SCIN(GV144-SCIN) to transfect hBMSCs, which were treated with different Ccs levels (0.25 Hz*5 cm, 0.5 Hz*5 cm, and 1 Hz*10 cm); the result showed that overexpression of Scin upregulated osteogenesis and osteoclastogenesis. By contrast, expression of chondrocyte-specific genes, including ACAN, COL-2A, and Sox9, decreased. Further molecular investigation demonstrated that Scin promoted osteogenesis and osteoclastogenesis through activation of the p-Smad1/5/8, NF-κB, and MAPK P38 signaling pathways, as well as stimulated the expression of key osteoclast transcriptional factors NFATc1 and c-Fos. Moreover, Scin-induced osteogenesis outweighed osteoclastogenesis in defective femur in vivo. The results of the analysis of Micro-CT confirmed these findings. Overall, Ccs influenced the development of DDH by promoting osteogenesis and cartilage degradation. In addition, Scin played a vital role in the development of DDH., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Y-box binding protein 1 (YB-1) belongs to the cold shock domain protein family involved in transcription and translation. We conducted a meta-analysis of the association between YB-1 expression and the survival and clinicopathological features in NSCLC., Methods: PubMed and Embase were searched to identify studies that evaluated the YB-1 expression (by immunohistochemistry) and overall survival (OS) in NSCLC. Hazard ratios (HRs) and 95% confidence intervals (CI) of OS were pooled. Odds ratios (ORs) of clinicopathological features were computed. Meta-analysis was performed using STATA 12.0 software., Results: Data on 692 NSCLC patients were collected from six eligible studies. Meta-analysis revealed that YB-1 was associated with worse OS (HR = 1.59, 95% CI [1.27, 2.00], P < 0.001, fixed effect), tumor stage (OR = 0.43, 95% CI [0.22-0.82], P = 0.01, random effect), and depth of invasion (OR = 0.37, 95%CI [0.22-0.63], P < 0.001, fixed effect). A subgroup was analyzed by IHC staining to determine the location of YB-1 positive expression. Poor OS was observed in nucleus staining (pooled HR = 1.86, 95% CI [1.41, 2.45], P < 0.001). However, no statistical significance was observed in combined cytoplasmic and nuclear staining (pooled HR = 1.14, 95% CI [0.76, 1.72], P = 0.536)., Conclusions: Meta-analysis indicated that YB-1 overexpression is correlated with worse OS and clinicopathological features in NSCLC. Subgroup analysis revealed that the nucleus expression of YB-1 may be more closely associated with NSCLC prognosis than cytoplasmic expression., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.