Exhalomics as a noninvasive method for assessing rumen fermentation in dairy cows: Can exhaled-breath metabolomics replace rumen sampling?

Previously, we used secondary electrospray ionization-mass spectrometry (SESI-MS) to investigate the diurnal patterns and signal intensities of exhaled (EX) volatile fatty acids (VFA) of dairy cows. The current study aimed to validate the potential of an exhalomics approach for evaluating rumen fermentation. The experiment was conducted in a switchback design, with 3 periods of 9 d each, including 7 d for adaptation and 2 d for sampling. Four rumen-cannulated original Swiss Brown (Braunvieh) cows were randomly assigned to 1 of 2 diet sequences (ABA or BAB): (A) low starch (LS; 6.31% starch on a dry matter basis) and (B) high starch (HS; 16.2% starch on a dry matter basis). Feeding was once per day at 0830 h. Exhalome (with the GreenFeed System), and rumen samples were collected 8 times to represent every 3 h of a day, and EX-VFA and ruminal (RM)-VFA were analyzed using SESI-MS and HPLC, respectively. Furthermore, the VFA concentration in the gas phase (HR-VFA) was predicted based on RM-VFA and Henry's Law (HR) constants. No interactions were identified between the types of diets (HS vs. LS) and the measurement methods on daily average VFA profiles (RM vs. EX or HR vs. EX), suggesting a consistent performance among the methods. Additionally, when the 3-h interval VFA data from HS and LS diets were analyzed separately, no interactions were observed between methods and time of day, indicating that the relative daily pattern of VFA molar proportions was similar regardless of the VFA measurement method used. The results revealed that the levels of acetate sharply increased immediately after feeding, trailed by an increase in the acetate:propionate ratio and a steady increase for propionate (2 h after feeding the HS diet, 4 h for LS), and butyrate. This change was more pronounced for the HS diet than the LS diet. However, there was no overall diet effect on the VFA molar proportions, although the measurement methods affected the molar proportions. Furthermore, we observed a strong positive correlation between the levels of RM and EX acetate for both diets (HS: r = 0.84; LS: r = 0.85), RM and EX propionate (r = 0.74), and RM and EX acetate:propionate ratio (r = 0.80). Both EX-VFA and RM-VFA exhibited similar responses to feeding and dietary treatments, suggesting that EX-VFA could serve as a useful proxy for characterizing RM-VFA molar proportions to evaluate rumen fermentation. Similar relationships were observed between RM-VFA and HR-VFA. In conclusion, this study underscores the potential of exhalomics as a reliable approach for assessing rumen fermentation. Moving forward, research should further explore the depth of exhalomics in ruminant studies to provide a comprehensive insight into rumen fermentation metabolites, especially across diverse dietary conditions.

Effects of 3-nitrooxypropanol (3-NOP, Bovaer®10) and whole cottonseed on milk production and enteric methane emissions from dairy cows under Swiss management conditions.

The objective of this study was to determine the potential effect and interaction of 3- nitrooxypropanol (3-NOP; Bovaer®) and whole cottonseed (WCS) on lactational performance, and enteric methane (CH4) emission of dairy cows. A total of 16 multiparous cows, including 8 Holstein Friesian (HF) and 8 Brown Swiss (BS) [224 ± 36 d in milk, 26 ± 3.7 kg milk yield], were used in a split-plot design, where the main plot was the breed of cows. Within each subplot, cows were randomly assigned to a treatment sequence in a replicated 4 × 4 Latin Square design with 2 × 2 factorial arrangements of treatments with 4, 24-d periods. The experimental treatments were: 1) Control (basal TMR), 2) 3-NOP (60 mg/kg TMR DM), 3) WCS (5% TMR DM), and 4) 3-NOP + WCS. The treatment diets were balanced for ether extract, crude protein, and NDF contents (4%, 16%, and 43% of TMR DM, respectively). The basal diets were fed twice daily at 0800 and 1800 h. Dry matter intake (DMI) and milk yield were measured daily, and enteric gas emissions were measured (using the GreenFeed system) during the last 3 d of each 24-d experimental period when animals were housed in tie stalls. There was no difference in DMI on treatment level, whereas the WCS treatment increased ECM yield and milk fat yield. There was no interaction of 3-NOP and WCS for any of the enteric gas emission parameters, but 3-NOP decreased CH4 production (g/d), CH4 yield (g/kg DMI), and CH4 intensity (g/kg ECM) by 13, 14 and 13%, respectively. Further, an unexpected interaction of breed by 3-NOP was observed for different enteric CH4 emission metrics: HF cows had a greater CH4 mitigation effect compared with BS cows for CH4 production (g/d; 18 vs. 8%), CH4 intensity (g/kg MY; 19% vs. 3%) and CH4 intensity (g/kg ECM; 19 vs. 4%). Hydrogen production was increased by 2.85 folds in HF and 1.53 folds in BS cows receiving 3-NOP. Further, there was a 3-NOP ' Time interaction for both breeds. In BS cows, 3-NOP tended to reduce CH4 production by 18% at around 4 h after morning feeding but no effect was observed at other time points. In HF cows, the greatest mitigation effect of 3-NOP (29.6%) was observed immediately after morning feeding and it persisted at around 23% to 26% for 10 h until the second feed provision, and 3 h thereafter, in the evening. In conclusion, supplementing 3-NOP at 60 mg/kg DM to a high fiber diet resulted in 18 to 19% reduction in enteric CH4 emission in Swiss Holstein Friesian cows. The lower response to 3-NOP by BS cows was unexpected and has not been observed in other studies. These results should be interpreted with caution due to low number of cows per breed. Lastly, supplementing WCS at 5% of DM improved ECM and milk fat yield but did not enhance CH4 inhibition effect of 3-NOP of dairy cows.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

Multiomics approach to profiling Sertoli cell maturation during development of the spermatogonial stem cell niche.

Spermatogonial stem cells (SSCs) are the basis of spermatogenesis, a complex process supported by a specialized microenvironment, called the SSC niche. Postnatal development of SSCs is characterized by distinct metabolic transitions from prepubertal to adult stages. An understanding of the niche factors that regulate these maturational events is critical for the clinical application of SSCs in fertility preservation. To investigate the niche maturation events that take place during SSC maturation, we combined different '-omics' technologies. Serial single cell RNA sequencing analysis revealed changes in the transcriptomes indicative of niche maturation that was initiated at 11 years of age in humans and at 8 weeks of age in pigs, as evident by Monocle analysis of Sertoli cells and peritubular myoid cell (PMC) development in humans and Sertoli cell analysis in pigs. Morphological niche maturation was associated with lipid droplet accumulation, a characteristic that was conserved between species. Lipidomic profiling revealed an increase in triglycerides and a decrease in sphingolipids with Sertoli cell maturation in the pig model. Quantitative (phospho-) proteomics analysis detected the activation of distinct pathways with porcine Sertoli cell maturation. We show here that the main aspects of niche maturation coincide with the morphological maturation of SSCs, which is followed by their metabolic maturation. The main aspects are also conserved between the species and can be predicted by changes in the niche lipidome. Overall, this knowledge is pivotal to establishing cell/tissue-based biomarkers that could gauge stem cell maturation to facilitate laboratory techniques that allow for SSC transplantation for restoration of fertility.

Intra-articular kinetics of a cartilage targeting cationic PEGylated protein for applications in drug delivery.

OBJECTIVES: Cartilage targeting cationic glycoprotein Avidin was PEGylated to synthesize a multi-arm Avidin (mAv) nano-construct with high drug loading content. Here we investigate mAv biodistribution and kinetics over a 7-day period following intra-articular (IA) administration in rat knee joints. METHODS: Labeled mAv was injected into healthy rat knees, and joint tissues (articular cartilage, menisci, ligaments, tendons, fat pad) were harvested following sacrifice at 6 h, 1, 4 and 7 days. Its IA biodistribution and retention were measured using fluorescence microscopy. Tissue localization was compared in young vs old rats by immunohistochemistry. mAv chondrotoxicity and immune response were evaluated to determine safe carrier dose limits. RESULTS: mAv penetrated through the full thickness of rat cartilage and other joint tissues within 6 h, remaining detectable within most joint tissues over 7 days. Intra-tissue uptake correlated strongly with tissue GAG concentration, confirming the dominant role of electrostatic interactions between positively charged mAv and the negatively charged aggrecan proteoglycans. mAv was uptaken by chondrocytes and also penetrated the osteocyte lacuno-canalicular system of peri-articular bone in both young and old rats. mAv did not cause cytotoxicity at concentrations up to 300 µM but elicited a dose dependent immunogenic response. CONCLUSIONS: mAv's ability to target a variety of joint tissues, chondrocytes, and peri-articular osteocytes without sequestration in synovial fluid makes it a versatile carrier for delivering a wide range of drugs for treating a broad class of musculoskeletal diseases. Drugs can be conjugated using simple aqueous based avidin-biotin reaction, supporting its clinical prospects.

Sustained intra-cartilage delivery of interleukin-1 receptor antagonist using cationic peptide and protein-based carriers.

OBJECTIVE: Blocking the interleukin-1 (IL-1) catabolic cascade following joint trauma can be achieved using its receptor antagonist, IL-1Ra. However, its clinical translation for osteoarthritis therapy has been unsuccessful due to its rapid joint clearance and lack of targeting and penetration into deep cartilage layers at therapeutic concentrations. Here, we target the high negative charge of cartilage aggrecan-glycosaminoglycans (GAGs) by attaching cationic carriers to IL-1Ra. IL-1Ra was conjugated to the cartilage targeting glycoprotein, Avidin, and a short length optimally charged cationic peptide carrier (CPC+14). It is hypothesized that electro-diffusive transport and binding properties of IL-1Ra-Avidin and IL-1Ra-CPC+14 will create intra-cartilage depots of IL-1Ra, resulting in long-term suppression of IL-1 catabolism with only a single administration. DESIGN: IL-1Ra was conjugated to Avidin or CPC+14 using site specific maleimide linkers, and confirmed using gel electrophoresis, high-performance liquid chromatography (HPLC), and mass spectrometry. Intra-cartilage transport and retention of conjugates was compared with native IL-1Ra. Attenuation of IL-1 catabolic signaling with one-time dose of IL-1Ra-CPC+14 and IL-1Ra-Avidin was assessed over 16 days using IL-1α challenged bovine cartilage and compared with unmodified IL-1Ra. RESULTS: Positively charged IL-1Ra penetrated through the full-thickness of cartilage, creating a drug depot. A single dose of unmodified IL-1Ra was not sufficient to attenuate IL-1-induced cartilage deterioration over 16 days. However, when delivered using Avidin, and to a greater extent CPC+14, IL-1Ra significantly suppressed cytokine induced GAG loss and nitrite release while improving cell metabolism and viability. CONCLUSION: Charge-based cartilage targeting drug delivery systems hold promise as they can enable long-term therapeutic benefit with only a single dose.

Goat Milk Based Infant Formula in Newborns: A Double-Blind Randomized Controlled Trial on Growth and Safety.

OBJECTIVES: We aimed to determine the growth and safety parameters in newborns fed a goat milk based infant formula (GMF) using a randomized double-blind trial, in which a cow milk formula (CMF) served as a control and a breast fed (BF) group as a reference. METHODS: Healthy term infants (n = 218) aged up to 14 days were recruited from 25 European study centers and randomized to GMF or CMF. Weight, length, head circumference were measured at baseline, and at 14, 28, 56, 84, and 112 days at the study clinics. Adverse events were recorded and stool characteristics, reflux, fussiness, colic, and flatulence were self-reported by parents in 3-day diaries. Anthropometric measurements were transformed to WHO standardized age- and sex-adjusted z -scores. Analyses of covariance and linear mixed modeling were used to statistically analyze growth, while adjusting for potential confounders when studying the breast-fed group (n = 86). RESULTS: Comparing the GMF to the CMF group, weight gain [mean difference 227.8 g (95% CI -16.6 to -439.0)] and z-scores for anthropometric measurements were similar after 112 days intervention. Infant formula groups showed greater mean (SD) weight z-scores than the BF group from 84 days onwards (GMF: 0.28 (0.84), CMF: 0.12 (0.88), BF -0.19 (1.02), P < 0.05), whereas length and head circumference z-scores were similar. Incidences of serious adverse events and reflux, fussiness, colic, and flatulence were similar among the three groups. CONCLUSION: Our data demonstrate that GMF provides adequate growth, has a good tolerability, and is safe to use in infants.

[Research progress of microvascular invasion in hepatocellular carcinoma].

Hepatocellular carcinoma (HCC) is a kind of highly aggressive tumor of the digestive system. Several studies have confirmed that microvascular invasion (MVI) is an independent risk factor for early recurrence and poor prognosis of HCC after surgery. Currently, pathological examination is the gold standard for diagnosing MVI. This paper summarizes concept, prognosis, preoperative prediction and treatment plan based on literature review of MVI in HCC.

Effect of radiomics from different virtual monochromatic images in dual-energy spectral CT on the WHO/ISUP classification of clear cell renal cell carcinoma.

AIM: To investigate the effect of radiomics obtained from different virtual monochromatic images (VMIs) in dual-energy spectral computed tomography (CT) on the World Health Organization/International Association for Urological Pathology (WHO/ISUP) classification of clear cell renal cell carcinoma (ccRCC). MATERIALS AND METHODS: A retrospective study of 99 ccRCC patients who underwent contrast-enhanced dual-energy CT was undertaken. ccRCC was confirmed at surgery or biopsy and graded according to the WHO/ISUP pathological grading criteria as low grade (n=68, grade I and II) or high grade (n=31, grade III and IV). Radiomics risk scores (RRSs) for differentiating high and low grades of ccRCC were constructed from 11 sets of VMI in (40-140 keV, 10 keV interval) the cortical phase. Receiver operating characteristic (ROC) curves were drawn and the area under the curves (AUCs) was calculated to evaluate the discriminatory power of RRS for each VMI. The Hosmer-Lemeshow test was used to evaluate the goodness-of-fit of each model and the decision curve was used to analyse its net benefit to patients. RESULTS: The AUC values for distinguishing low-from high-grade ccRCC with RRS of 40-140 keV VMIs were all >0.920. The Hosmer-Lemeshow test showed that the p-values of RRS of VMIs were >0.05, suggesting good fits. In the decision curve analysis, RRS from the 40-140 keV VMIs had similar decision curves and provided better net benefits than considering all patients either as high-grade or low-grade. CONCLUSIONS: The RRS obtained from multiple VMIs in dual-energy spectral CT have high diagnostic efficiencies for distinguishing between low- and high-grade ccRCC with no significant differences between different VMIs.

An in-vitro study on a novel six-phage cocktail against multi-drug resistant-ESBL Shigella in aquatic environment.

Shigella spp. are water-borne pathogens responsible for mild to severe cases bacilli dysentery all around the world known as Shigellosis. The progressively increasing of antibiotic resistance among Shigella calls for developing and establishing novel alternative therapeutic methods. The present study aimed to evaluate a novel phage cocktail of lytic phages against extended spectrum beta lactamase isolates of Shigella species in an aquatic environment. The phage cocktail containing six novel Shigella specific phages showed a broad host spectrum. The cocktail was very stable in aquatic environment. The cocktail resulted in about 99% decrease in the bacterial counts in the contaminated water by several species and strains of Shigella such as Shigella sonnei, Shigella flexneri and Shigella dysenteriae. Achieving such a high efficiency in this in-vitro study demonstrates a high potential for in-vivo and in-situ application of this phage cocktail as a bio-controlling agent against Shigella spp. contamination and infections.

Gout in China, 1990-2017: the Global Burden of Disease Study 2017.

OBJECTIVE: The aim of the study was to estimate the gout burden and risk factors in China from 1990 to 2017. STUDY DESIGN: The Global Burden of Disease (GBD) Study uses various analytical tools and a diverse set of data sources to generate comparable estimates of deaths and mortality rates broken down by age, sex, cause, year, and geography. METHODS: We used the results from the GBD Study 2017 to compare disability-adjusted life years (DALYs), prevalence, incidence, and risk factors of gout in China. The median of the percentage change and 95% uncertainty intervals were determined for the period between 1990 and 2017. RESULTS: The age-standardized DALY rate, prevalence, and incidence increased 6.92%, 6.88%, and 6.16%, respectively, in China from 1990 to 2017. Although the rates of gout both globally and in China were increasing, the range of change for males in China was larger than that of the global level. All risk factors combined accounted for 30.04% of gout DALYs in 2017. The leading risk factors for gout DALYs were high body mass index and impaired kidney function, and the proportion of high body mass index increased significantly from 10.67% to 24.31%, whereas the proportion of impaired kidney function remained basically unchanged. CONCLUSIONS: The age-standardized DALY rate, prevalence, and incidence in China have increased progressively since 1990. Increasing attention on body weight management should be prioritized for controlling the rising prevalence of gout in the young and middle-aged population.

[Effect and mechanism of siRNA targeting α-enolase gene combined with paclitaxel on proliferation, invasion and apoptosis of hepatocellular carcinoma cell].

Objective: To investigate the effect of siRNA targeting inhibition of α-enolase (ENO1) combined with paclitaxel on the proliferation, invasion and apoptosis of hepatocellular carcinoma SK-HEP-1 cell and its mechanism. Methods: siRNA-ENO1 (siRNA-ENO1 group) and siRNA-negative control (siRNA-NC group) were transfected into SK-HEP-1 cells in vitro, the untransfected SK-HEP-1 cells were used as the control group, and the transfection effect was detected by real-time fluorescent quantitative polymerase chain reaction and western blotting. After SK-HEP-1 cells were treated with 0, 2.5, 5, 10, 20 and 40 µg/L paclitaxel for 48 hours, the cell survival rate was measured by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) method and the semi inhibitory concentration of paclitaxel was calculated. SK-HEP-1 cells transfected with siRNA-ENO1 or siRNA-NC were treated with 10 µg/L paclitaxel as paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group. The proliferation, clonogenesis, invasion and apoptosis of siRNA-NC group, siRNA-ENO1 group, paclitaxel+ siRNA-ENO1 group and paclitaxel+ siRNA-NC group were detected by MTT, clonogenesis, Transwell chamber and flow cytometry respectively. The expression levels of the phosphorylation of phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (Akt) and proliferating cell nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP-9) and B lymphocytoma-2 gene (Bcl-2) were detected by western blotting. Results: Compared with the control group (1.00±0.00 and 0.69±0.04, respectively), the expression levels of ENO1 mRNA and protein (0.25±0.03 and 0.23±0.02, respectively) in siRNA-ENO1 group decreased significantly (P<0.05), but there were no significant differences in the expression levels of ENO1 mRNA and protein in siRNA-NC group (P>0.05). Compared without treatment group [(100.00±0.00)%, P<0.05], the survival rates of SK-HEP-1 cells treated with 2.5, 5, 10, 20 and 40 µg/L paclitaxel [(88.65±6.46)%, (72.36±6.08)%, (60.48±4.23)%, (38.52±3.56)% and (20.75±2.32)%, respectively] decreased significantly (P<0.05), and the semi inhibitory concentration of paclitaxel was 13.26 µg/L. The cell survival rate and clone formation rate of siRNA-ENO1 group [(68.86±5.12)% and (18.12±2.25)%, respectively] were lower than those of siRNA-NC group [(100.00±0.00)% and (29.65±3.06)%, respectively, P<0.05]. The cell survival rate and clone formation rate of the paclitaxel+ siRNA-ENO1 group [(43.28±2.64)% and (8.72±0.52)%, respectively] were significantly different from those of the paclitaxel+ siRNA-NC group [(61.75±5.06)% and (13.48±2.16)%, respectively, P<0.05] and siRNA-ENO1 groups [(68.86±5.12)% and (18.12±2.25)%, respectively, P<0.05]. Cell invasion number in paclitaxel+ siRNA-ENO1 group (23.64±2.12) was lower than that in siRNA-ENO1 group and paclitaxel+ siRNA-NC group (42.16±2.75 and 37.35±2.42, respectively, P<0.05). The apoptosis rates of paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively] were higher than that of siRNA-NC group [(7.21±0.70)%, P<0.05]. The apoptosis rate in the paclitaxel+ siRNA-ENO1 group [(24.59±2.40)%] was higher than those in the paclitaxel+ siRNA-NC group and siRNA-ENO1 group [(17.49±1.35)% and (15.29±1.50)%, respectively, P<0.05]. The expression levels of ENO1, PI3K/Akt signaling pathway related proteins including p-PI3K and p-Akt and the expression levels of PCNA, MMP-9 and Bcl-2 in siRNA-ENO1 group and paclitaxel+ siRNA-NC group were lower than those in siRNA-NC group (P<0.05). The expression levels of ENO1, p-PI3K, p-Akt, PCNA, MMP-9 and Bcl-2 in paclitaxel+ siRNA-ENO1 group were lower than those in siRNA-ENO1 group or paclitaxel+ siRNA-NC group (P<0.05). Conclusion: siRNA targeting inhibition of ENO1 expression can enhance the inhibitory effect of paclitaxel on proliferation, invasion and apoptosis of SK-HEP-1 cells, and its mechanism may be related to the inhibition of PI3K/AKT signaling pathway.

[The composition of ascites lymphocytes in high-grade serous ovarian cancer and its correlation with clinical features].

Objective: To explore the composition of ascites lymphocytes in high-grade serous ovarian carcinoma (HGSOC) and its correlation with clinical features. Methods: A total of 59 newly-diagnosed HGSOC patients, aged (58±11) years old, who were treated at the Department of Obstetrics and Gynecology of Peking University Third Hospital from July 2019 to December 2020 were included, collecting ascites and peritoneal irrigation fluid respectively. Detect the proportion of T, B, NK cell and its subpopulations by flow cytometry, and analyze its correlation with the clinical characteristics of patients. Results: Among 59 patients, 48 patients (81.4%) had ascites, and 11 patients (18.6%) had no ascites. Compared with the peritoneal irrigation fluid, the CD3+T (70.2%±15.6% vs 78.1%±6.7%, P=0.014), CD8+T (38.3%±11.2% vs 47.7%±10.1%, P=0.014) and CD16-CD56bright NK [2.0% (0.8%, 3.6%) vs 4.2% (1.5%, 7.1%), P=0.026] cells were significantly decreased in the ascites, while the CD16+CD56dim NK cells was significantly increased [6.8% (2.8%, 15.7%) vs 2.6% (1.6%, 4.3%), P=0.008]. In patients with ascites volume ≥1 000 ml, CD16-CD56bright NK cells were significantly increased than those ascites volume<1 000 ml [3.1% (1.2%, 3.9%) vs 0.8% (0.4%, 2.3%), P=0.002]. Age was significantly positively correlated with the level of CD4+T cells (r=0.332, P=0.021) and the ratio of CD4+T/CD8+T (r=0.379, P=0.008) in ascites. In ascites from patients with poor response to treatment, the proportion of CD4+T cells was increased significantly than those with better response (64.7%±4.2% vs 48.3%±11.7%, P=0.002). Conclusion: The formation of ascites in newly diagnosed high-grade serous epithelial ovarian cancer patients would affect the lymphocyte composition in the abdominal cavity microenvironment, which is related to the patient's age, cancer progression and treatment response.

[Correlation analysis between serum ferritin level and liver damage in acute stage of dengue fever].

Objective: To investigate the correlation between serum ferritin (SF) level and liver damage in the acute stage of dengue fever. Methods: A retrospective study was conducted to analyze 171 cases diagnosed with dengue fever as dengue fever group and 130 healthy patients as control group in Hangzhou 3A grade hospital from July to December 2017. Clinical data, SF and liver function related indicators were collected from both groups: alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL) to analyze the correlation between liver damage and SF in patients with dengue fever. Results: ALT, AST, and SF levels were significantly higher in the dengue fever group than those in the healthy control group (Z = 11.553, 15.054 and 15.163, P < 0.001). SF levels were higher in the dengue fever combined with liver damage group than those without the liver damage group (z = 6.930, P < 0.001). However, there was no statistically significant differences in age, gender, peak body temperature, and history of liver disease (P > 0.05). In addition, Spearman's correlation analysis showed that SF was positively correlated with ALT, AST, and TBIL (r = 0.464, 0.531 and 0.315, P < 0.001). Among dengue patients with different SF levels, there were significant difference in ALT, AST levels and incidence of liver damage (H = 14.240 and 17.584, χ(2) = 49.547, P < 0.001). Patients with higher SF levels had higher ALT, AST levels and incidence of liver damage. Binary logistic regression analysis showed that hyperferritinemia (SF≥500 ng/ml) was the risk factor for dengue fever combined with liver damage (OR = 8.120, P < 0.001). Furthermore, ROC curve analysis showed that the AUC for SF to judge dengue fever combined liver damage was 0.846 (95% CI: 0.785-0.908), and the sensitivity and specificity when the SF cut-off value was 1 506 ng/ml were 74.8% and 83.3%. Conclusion: There is a certain correlation between the SF level and the degree of liver damage in acute stage of dengue fever patients, and hyperferritinemia is a risk factor for dengue fever combined with liver damage.

Predicting the intervention threshold for initiating osteoporosis treatment among postmenopausal women in China: a cost-effectiveness analysis based on real-world data.

This study built a micro-simulation Markov model to determine the treatment threshold of osteoporosis in postmenopausal women in Mainland China. Treatment with zoledronate is cost-effective when FRAX-based (Fracture risk assessment tool) fracture probability is over 7%. INTRODUCTION: The purpose of this study is to estimate FRAX-based fracture probabilities in Mainland China using real-world data, at which intervention could be cost-effective. METHODS: We developed a micro-simulation Markov model to capture osteoporosis states and relevant morbidities including hip fracture, vertebral fracture, and wrist fracture. Baseline characteristics including incidences of osteoporosis and distribution of risk factors were derived from the Peking Vertebral Fracture study, the largest prospective cohort study of postmenopausal women in Mainland China. We projected incidences of fractures and deaths by age groups under two treatment scenarios: 1) no treatment, and 2) zoledronate. We also projected total quality-adjusted life-years (QALY) and total costs including fracture management and osteoporosis drugs for cost-effectiveness analysis. Cost-effective intervention thresholds were calculated based on the Chinese FRAX model. RESULTS: Treatment with zoledronate was cost-effective when the 10-year probability of major osteoporotic fracture based on FRAX was above 7%. The FRAX threshold increased by age from 51 to 65 years old, and decreased in elder age groups, ranging from 4% to 9%. CONCLUSIONS: Using real-world data, our model indicated that widespread use of zoledronate was of both clinical and economic benefit among Chinese postmenopausal women. Using a FRAX-based intervention threshold of 7% with zoledronate should permit cost-effective access to therapy to patients and contribute to reducing the disease burden of osteoporosis in Mainland China.

Gut microbiota differences during metamorphosis in sick and healthy giant spiny frogs (Paa spinosa) tadpoles.

Gut microbiota plays important roles in host nutrition, immunity, development and health; therefore, disruption of the gut microbiota is closely associated with development of diseases in the host. In amphibians, metamorphosis is associated not only with extensive changes in the gut microbiota, but also with high mortality. Therefore, we hypothesized that unsuccessful restructuring of the gut microbiota during metamorphosis was an important factor that caused the fatalities. To test this hypothesis, we investigated the gut microbiota of apparently sick and healthy giant spiny frog tadpoles during metamorphosis, using high-throughput sequencing of the 16S rRNA gene. Our results showed that most dominant phyla differed significantly among developmental stages of sick and healthy Paa spinosa tadpoles. The differences in the dominant genera in sick and healthy tadpoles were the highest at the stage of degeneration of cloacal tube (TDCT). After the metamorphosis, the composition of the gut microbiota was more alike between healthy and sick tadpoles at the stage of forelimb emergence than at TDCT. These results imply that failed restructuring of the gut microbiota during metamorphosis caused the death of P. spinosa tadpoles. These results provided an important reference to prevent the high actual of P. spinosa tadpoles during metamorphosis. SIGNIFICANCE AND IMPACT OF THE STUDY: We investigated the gut microbiota of apparently sick and healthy giant spiny frog (Paa spinosa) tadpoles during metamorphosis, using high-throughput sequencing of the 16S rRNA gene. Our results showed that the differences in the dominant genera in sick and healthy tadpoles were the highest at the stage of degeneration of cloacal tube. After the metamorphosis, the composition of the gut microbiota was alike between healthy and sick tadpoles. These results imply that failed restructuring of the gut microbiota during metamorphosis caused the death of P. spinosa tadpoles.

[Anti-PD-1 therapy in advanced malignant liver tumor-induced type-1 diabetes mellitus: a case report].

Immune checkpoint inhibitor (ICI) has been emerged as a major breakthrough in tumor immunotherapy, but its unique mechanism of action has also led to a number of immune-related adverse events (irAE). Type 1 diabetes mellitus (T1DM) is one of the rarest irAEs. This paper reports a case of advanced malignant liver tumor-induced T1DM who received second-line anti-PD-1 therapy and showed initial symptoms of hyperosmolar coma and hyperglycemia. In addition, the relevant literature at home and abroad was collected and reviewed, and the clinical characteristics of T1DM induced by anti-PD-1 therapy were summarized with a view to achieve early detection, diagnosis and treatment.

[Application of adaptive statistical iterative reconstruction veo and 80 kv in renal computed tomography angiography].

Objective: To explore the application of adaptive statistical iterative reconstruction Veo (ASIR-V) and 80 kV in renal computed tomography angiography(CTA). Methods: Eighty patients with renal computed tomography angiography were prospectively collected from April 2018 to July 2018 in the Affiliated Hospital of Shaanxi University of Chinese Medicine and randomly divided into group A and group B. The patients in group A adopted tube voltage 120 kV and contrast agent concentration 600 mgI/kg and reconstructed with filtered back projection (FBP), while the patients in group B were scanned with tube voltage 80 kV and contrast agent concentration 350 mgI/kg and reconstructed with FBP and ASIR-V from 10% to 100% with 10% interval. The CT values and standard deviation (SD) of the right renal artery, left renal artery were measured respectively to calculate the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR).The image quality of renal CTA was subjectively scored by two experienced radiologists blindly using a 5-point criteria.The contrast agent,CT volume dose index(CTDI(vol)) and dose length product(DLP) in both groups were recorded and the effective radiation dose(ED) was calculated. Results: The ED ((2.11±0.19)mSv) and contrast agent ((21.9±3.0)g) in group B were 65.1% (P<0.05) and 42.2% (P<0.05) lower than those in group A ((6.04±1.89)mSv and (38.0±3.8)g).With the increase of ASIR-V percentage in group B, CT values showed no significant difference, SD values gradually decreased, SNR values and CNR values gradually increased.The CT values with different reconstruction algorithm showed no statistically significant difference (all P>0.05) between group A and group B. The SD values with 40%ASIR-V to 100%ASIR-V reconstruction in group B were significantly lower than those of group A (all P<0.05).The SNR values with 50% ASIR-V to 100% ASIR-V reconstruction and CNR values with 70%ASIR-V to 100%ASIR-V were significantly higher than those of group A(all P<0.5).Two radiologists had excellent consistency in subjective scores of image quality for renal CTA(all kappa>0.75, P<0.05). The subjective scores with 60% ASIR-V to 90% ASIR-V in group B were significantly higher than those in group A (P<0.05), of which 70%ASIR-V reconstruction achieved the highest subjective score for renal CTA. Conclusion: ASIR-V and 80 kV can significantly reduce radiation dose (about 65.1%) and contrast agent (about 42.2%) in renal CTA, ASIR-V reconstruction can significantly improve the image quality of renal CTA, of which 70% ASIR-V reconstruction achieved the best image quality in 80 kV renal CTA.

[Analysis of prognostic factors for hyperamylasemia following pancreaticoduodenectomy].

Objective: To investigate the prognostic factors of hyperamylasemia following pancreaticoduodenectomy (PD) . Methods: Clinical data of 359 patients were collected prospectively who underwent PD by the same group at Changhai Hospital of Navy Medical University from January 2017 to June 2018.There were 212 males and 147 females.The median age was 63 years old (range: 23 to 82 years old) .According to whether the patient's serum amylase was greater than 120 U/L at 0 or 1 day after surgery,the patients were divided into hyperamylasemia group and non-hyperamylasemia group. Univariate analysis and multivariate analysis were used to find out the prognostic factors of hyperamylasemia after PD. Results: Of the 359 patients, 238 cases (66.3%) developed hyperamylasemia.The incidence rate of clinically related pancreatic fistula (15.1% vs.2.5%, P<0.01) , grade B/C post pancreatectomy hemorrhage (8.8% vs. 2.5%, P<0.01) , and surgical site infection (9.2% vs. 3.3%, P=0.04) was significantly higher in the hyperamylasemia group.The severity of complications (CD grade≥Ⅲ: 11.3% vs.4.1%, P=0.023) and postoperative hospital stay (11 days vs. 9 days, P=0.001) were higher in the hyperamylasemia group.In the multivariate analysis, the main pancreatic duct diameter (MPD) ≤3 mm (OR=4.469, 95% CI: 2.563-7.793, P<0.01) , pathological type of disease (pancreatic cancer or pancreatitis) (OR=0.230, 95% CI: 0.122-0.436, P<0.01) and soft texture of pancreas (OR=3.297, 95%CI: 1.930-5.635, P<0.01) were independent prognostic factors for hyperamylasemia. Conclusions: Post-PD hyperamylasemia increased the incidence and severity of postoperative complications after PD.MPD≤3 mm, soft texture of pancreas and pathological type of disease were independent prognostic factors of hyperamylasemia.

Chronic obstructive pulmonary disease deaths, disability-adjusted life years, and risk factors in Hubei province of mid-China, 1990-2015: the Global Burden of Disease Study 2015.

OBJECTIVES: The trends of chronic obstructive pulmonary disease (COPD) mortality and prevalence from 1990 to 2015 in Hubei province of mid-China remain unknown. We used findings from the Global Burden of Disease (GBD) 2015 study to estimate the COPD burden and attributable to risk factors in Hubei province of China from 1990 to 2015. STUDY DESIGN: The GBD study uses various analytical tools and a diverse set of data sources to generate comparable estimates of deaths and mortality rates broken down by age, sex, cause, year, and geography. METHODS: Data were extracted from the GBD 2015 study. Statistical models were used to produce comprehensive results of COPD deaths, prevalence, disability-adjusted life years (DALYs), years of life lost, years lived with a disability, and attributable to risk factors in Hubei. The median of the percent change and 95% uncertainty intervals were determined for the period between 1990 and 2015. RESULTS: In 2015, there were 37,144 deaths from COPD in Hubei, accounting for 10.05% of the total deaths in Hubei. The age-standardized COPD death rate was reduced by 60.28% from 188.67 per 100,000 (in 1990) to 74.94 per 100,000 (in 2015). The age-standardized prevalence decreased from 4.30% (1990) to 2.85% (2015). By 2015, the leading risk factors for all ages COPD DALYs were smoking and ambient particulate matter pollution, accounting for 44.69% and 32.91%, respectively. The proportion of ambient ozone pollution was increasing steadily each year since 1990. CONCLUSION: Hubei has made substantial progress in reducing the mortality due to COPD since 1990, but the absolute number of COPD cases is increasing steadily, given the population growth and aging. The increasing contribution from smoking, ambient particulate matter pollution, and ambient ozone pollution should require growing attention.