Adverse birth outcomes related to concentrations of per- and polyfluoroalkyl substances (PFAS) in maternal blood collected from pregnant women in 1960-1966.

BACKGROUND: Prior animal and epidemiological studies suggest that per- and polyfluoroalkyl substances (PFAS) exposure may be associated with reduced birth weight. However, results from prior studies evaluated a relatively small set of PFAS. OBJECTIVES: Determine associations of gestational PFAS concentrations in maternal serum samples banked for 60 years with birth outcomes. METHODS: We used data from 97 pregnant women from Boston and Providence that enrolled in the Collaborative Perinatal Project (CPP) study (1960-1966). We quantified concentrations of 27 PFAS in maternal serum in pregnancy and measured infant weight, height and ponderal index at birth. Covariate-adjusted associations between 11 PFAS concentrations (>75% detection limits) and birth outcomes were estimated using linear regression methods. RESULTS: Median concentrations of PFOA, PFNA, PFHxS, and PFOS were 6.189, 0.330, 14.432, and 38.170 ng/mL, respectively. We found that elevated PFAS concentrations during pregnancy were significantly associated with lower birth weight and ponderal index at birth, but no significant associations were found with birth length. Specifically, infants born to women with PFAS concentrations ≥ median levels had significantly lower birth weight (PFOS: ß = -0.323, P = 0.006; PFHxS: ß = -0.292, P = 0.015; PFOA: ß = -0.233, P = 0.03; PFHpS: ß = -0.239, P = 0.023; PFNA: ß = -0.239, P = 0.017). Similarly, women with PFAS concentrations ≥ median levels had significantly lower ponderal index (PFHxS: ß = -0.168, P = 0.020; PFHxA: ß = -0.148, P = 0.018). CONCLUSIONS: Using data from this US-based cohort study, we found that 1) maternal PFAS levels from the 1960s exceeded values in contemporaneous populations and 2) that gestational concentrations of certain PFAS were associated with lower birth weight and infant ponderal index. Additional studies with larger sample size are needed to further examine the associations of gestational exposure to individual PFAS and their mixtures with adverse birth outcomes.

Associations between abdominal obesity indices with hypertension in type 2 diabetes mellitus: Chinese visceral adiposity index.

PURPOSE: This research was performed to evaluate the relationship between hypertension (HTN) and abdominal obesity index in patients with type 2 diabetes mellitus (T2DM). METHODS: Totally 1657 participants with T2DM (mean age 54 ± 12 years; 38.02% female) were enrolled. They were divided into the groups of HTN (n = 775) and non-HTN (n = 882). Anthropometric and biochemical indicators were measured and collected. A bioelectrical impedance analyzer was used to measure visceral and subcutaneous fat areas. RESULTS: Compared with the HTN group, the non-HTN group had a lower level of Chinese visceral adiposity index (CVAI) (p < 0.001). Meanwhile, among tertiles of CVAI, as CVAI increased, the proportion of patients with HTN increased, which was 33.51%, 44.30%, and 62.50%, respectively. CVAI was shown to have a significant positive correlation with HTN. (r = 0.258, p < 0.001). CVAI was independently related to an elevated risk of HTN by binary logistic regression analyses, and the OR was (95% CI) 1.013 (1.010-1.016, p < 0.001) after adjustment. The area under the receiver operating characteristic curve (AUC) of CVAI predicted HTN in T2DM patients was greater than those of other abdominal obesity indices (p < 0.001). CONCLUSION: We found that CVAI was highly positively correlated with HTN in T2DM. Compared with other indices of abdominal obesity, such as WC, BMI, WHR, VAI, and LAP, the CVAI showed superior discriminative ability in T2DM complicated with HTN. Therefore, more attention should be paid to CVAI in T2DM.

A deep neural network for parametric image reconstruction on a large axial field-of-view PET.

PURPOSE: The PET scanners with long axial field of view (AFOV) having ~ 20 times higher sensitivity than conventional scanners provide new opportunities for enhanced parametric imaging but suffer from the dramatically increased volume and complexity of dynamic data. This study reconstructed a high-quality direct Patlak Ki image from five-frame sinograms without input function by a deep learning framework based on DeepPET to explore the potential of artificial intelligence reducing the acquisition time and the dependence of input function in parametric imaging. METHODS: This study was implemented on a large AFOV PET/CT scanner (Biograph Vision Quadra) and twenty patients were recruited with 18F-fluorodeoxyglucose (18F-FDG) dynamic scans. During training and testing of the proposed deep learning framework, the last five-frame (25 min, 40-65 min post-injection) sinograms were set as input and the reconstructed Patlak Ki images by a nested EM algorithm on the vendor were set as ground truth. To evaluate the image quality of predicted Ki images, mean square error (MSE), peak signal-to-noise ratio (PSNR), and structural similarity index measure (SSIM) were calculated. Meanwhile, a linear regression process was applied between predicted and true Ki means on avid malignant lesions and tumor volume of interests (VOIs). RESULTS: In the testing phase, the proposed method achieved excellent MSE of less than 0.03%, high SSIM, and PSNR of ~ 0.98 and ~ 38 dB, respectively. Moreover, there was a high correlation (DeepPET: [Formula: see text]= 0.73, self-attention DeepPET: [Formula: see text]=0.82) between predicted Ki and traditionally reconstructed Patlak Ki means over eleven lesions. CONCLUSIONS: The results show that the deep learning-based method produced high-quality parametric images from small frames of projection data without input function. It has much potential to address the dilemma of the long scan time and dependency on input function that still hamper the clinical translation of dynamic PET.

Prediction of synchronous distant metastasis of primary pancreatic ductal adenocarcinoma using the radiomics features derived from 18F-FDG PET and MRI.

AIM: To explore the potential of the joint radiomics analysis of positron-emission tomography (PET) and magnetic resonance imaging (MRI) of primary tumours for predicting the risk of synchronous distant metastasis (SDM) in patients with pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: 18F-FDG PET and MRI images of PDAC patients from January 2011 to December 2020 were collected retrospectively. Patients (n=66) who received 18F-FDG PET/CT and MRI were included in a development group. Patients (n=25) scanned with hybrid PET/MRI were incorporated in an external test group. A radiomics signature was constructed using the least absolute shrinkage and selection operator algorithm to select PET-MRI radiomics features of primary PDAC tumours. A radiomics nomogram was developed by combining the radiomics signature and important clinical indicators using univariate and multivariate analysis to assess patients' metastasis risk. The nomogram was verified with the employment of an external test group. RESULTS: Regarding the development cohort, the radiomics nomogram was found to be better for predicting the risk of distant metastasis (area under the curve [AUC]: 0.93, sensitivity: 87%, specificity: 85%) than the clinical model (AUC: 0.70, p<0.001; sensitivity:70%, specificity: 65%) and the radiomics signature (AUC: 0.89, p>0.05; sensitivity: 65%, specificity:100%). Concerning the external test cohort, the radiomics nomogram yielded an AUC of 0.85. CONCLUSION: PET-MRI based radiomics analysis exhibited effective prediction of the risk of SDM for preoperative PDAC patients and may offer complementary information and provide hints for cancer staging.

[Fuzheng Huayu capsules reducing development of hepatocellular carcinoma in cirrhotic patients with chronic hepatitis B based on the ratio of neutrophils/lymphocytes].

Objective: To explore the advantage of Fuzheng Huayu capsule in patients with hepatitis B cirrhosis based on neutrophil/lymphocyte ratio (NLR) risk stratification in reducing the incidence of hepatocellular carcinoma (HCC). Methods: 916 cases diagnosed with hepatitis B cirrhosis and followed up for five years from January 2011 to January 2016 at Beijing Ditan Hospital Affiliated with Capital Medical University were included, and clinical data were collected. Patients were divided into a combination group and an antiviral group according to whether they were treated with anti-fibrosis for≥6 months. The antiviral group was treated with entecavir or tenofovir disoproxil, while the combination group was treated with Fuzheng Huayu capsules based on the antiviral therapy. The incidence of HCC was compared between the two groups of patients within five years. The advantaged groups treated with Fuzheng Huayu capsule were explored based on NLR risk stratification. The independent sample t-test and Mann-Whitney U test were used to compare measurement data between two groups. Categorical variable data were compared using either the χ(2) test or Fisher's exact probability method. The incidence of HCC in the two groups of patients was analyzed through the Kalplan-Merier curve and compared using the log-rank method. Results: There were 299 (32.6%) and 617 (67.4%) cases in the combined group and the antiviral group, respectively. A total of 154 (16.8%) patients developed HCC during the follow-up period. The five-year cumulative incidence of HCC in the combination group was lower than that in the antiviral group (10.7% vs. 19.8%, χ(2) = 11.848, P = 0.000 4). Patients with baseline NLR>3 had an increased risk of HCC. According to NLR risk stratification, there were 191 cases in the low-risk group (NLR<1.4), 462 cases in the medium-risk group (NLR1.4 ~ 3.0), and 263 cases in the high-risk group (NLR>3). Among medium to high-risk patients, the incidence of HCC was significantly reduced in the combination group (11.5% vs. 19.4%, χ(2) = 4.519, P = 0.029; 13.2% vs. 26.2%, χ(2) = 5.258, P = 0.019), while there was no statistically significant difference in the incidence of HCC among the low-risk group (P = 0.38). Conclusion: Compared with antiviral treatment alone, Fuzheng Huayu capsules combined with antiviral treatment can better reduce the five-year HCC incidence rate in patients with hepatitis B cirrhosis. Medium-and high-risk patients with NLR stratification are the most advantageous population to be treated with Fuzheng Huayu capsules.

[Investigation and analysis of prevalence of musculoskeletal diseases among interventional surgeons in some top three hospitals in Tianjin].

Objective: To analyze the prevalence and risk factors of musculoskeletal diseases among interventional surgeons in top three hospitals, and to provide suggestions for prevention of musculoskeletal diseases. Methods: In June 2022, a self-designed questionnaire was used to collect general information of doctors engaged in interventional surgery (121) and non-interventional surgery (124) in some top three hospitals in Tianjin. The standard version of the Nordic Musculoskeletal Questionnaire was used to investigate information related to musculoskeletal diseases. The prevalence and risk factors of musculoskeletal diseases among interventional and non-interventional surgeons were analyzed. Results: The prevalence of musculoskeletal diseases among interventional surgeons and non-interventional surgeons was 59.50% (72/121) and 62.90% (78/124) . Compared with non-interventional surgeons, interventional surgeons had a higher prevalence of musculoskeletal diseases in the shoulders and upper back, and a lower prevalence of musculoskeletal diseases in the waist. The differences were statistically significant (P<0.05) . Multivariate logistic regression analysis showed that age, weekly time of physical exercise, time of intervention operation, and wearing protective clothing were independent risk factors for musculoskeletal diseases (P<0.05) . Conclusion: The prevalence rate of musculoskeletal diseases among doctors engaged in interventional surgery is relatively high in some top three hospitals in Tianjin, and proper enhancement of physical exercise and shortening of interventional time are conducive to reducing musculoskeletal diseases.

Novel biomarkers of intervertebral disc cells and evidence of stem cells in the intervertebral disc.

OBJECTIVE: Rat intervertebral disc (IVD) is one of the most commonly used and cost-effective alternative models for human IVD. Many IVD related clinical studies need to be pre-tested on rat IVDs. However, studies on the heterogeneous cell clusters of the rat IVD are inadequate, and a further understanding of the marker genes and cell phenotypes of healthy mature IVD cells is essential. METHODS: In this study, we used the 10X Genomics technology to analyze the single-cell transcriptome of purified wild-type rat IVDs. RESULTS: We identified potentially new gene markers of IVDs via single-cell sequencing. Based on the unsupervised cluster analysis of 13,578 single-cell transcripts, 3 known IVD cell types were identified. We provided a complete single-cell gene expression map of the IVD. Immunohistochemical and immunofluorescence images of rat disc sections confirmed the new marker genes of all cell types. One group of heterologous cell groups expressed multi-functional stem cell (MSC)-specific genes, indicating the stem cell potential of IVD cells. CONCLUSION: We provided the phenotype and marker genes of IVD cells at the single-cell level, reconfirmed existing data, and proposed new marker genes, including MSC marker genes. By identifying more accurate target cells and genes, our results pave the way for further study of the response of individual disc cells to disease states and provide the basis for future disc regeneration therapies.

[Digital and anatomical study of posterior atlantooccipital joint-occipital condyle-clivus screw technique].

Objective: To investigate the screw placement parameters, feasibility and safety of posterior atlantooccipital joint-occipital condyle-clivus screw technique in Chinese people. Methods: Upper cervical spine CT images of 46 patients, including 24 males and 22 females, were collected with random number table from June 2019 to May 2020 in Ningbo No.6 Hospital. The patients aged 20-55 years, with a mean age of (39±9) years. Total of 92 sides of upper cervical spine models were obtained by Mimics 19.0 digital three-dimensional reconstruction, and screw placement was conducted simulately. The midpoint of transition zone between the posterior arch of atlas and the inferior articular process of lateral mass was selected as the screw entry point. The diameter and length of screws was 3.5 mm and 50 mm, respectively. Detailed morphometric measurements of the 92 atlantooccipital joint-occipital condyle-clivus screws were conducted. The distance between the screw and its surrounding important structures, screw inside and upper tilting angles, the length of screw trajectory in atlas and the length of screw trajectory on occipital side (occipital condyle-clivus) were all measured. Paired t test was performed on the parameters of left and right screw placement to confirm whether there was difference between the two sides. Results: In the 46 cases of upper cervical spine digital three-dimensional models, 92 posterior atlantooccipital joint-occipital condyle-clivus screws were implanted. All the screws were completely fixed in the clivus, without breaking through the upper sphenoid sinus, entering into the canalis spinalis and foramen magnum, and damaging the surrounding structures such as hypoglossal canal. The screw trajectory parameters between the left and right sides were slightly different, but there was no statistical differences between the two sides (P>0.05). The vertical distance between the screw entry point and the upper edge of atlas was (12.6±1.0) mm, the vertical distance between the screw entry point and the lower edge of atlas was (6.5±0.6) mm, the distance between the screw and the medial border of atlas vertebral artery foramen was (6.7±0.6) mm, the distance between the screw entry point and the medial wall of atlas was (6.6±0.7) mm, the distance between the screw outer margin and the hypoglossal canal was (5.5±0.6) mm, screw inside tilting angle was 21.2°±2.5°, screw upper tilting angle was 52.0°±3.4°, the length of screw trajectory in atlas was (12.1±0.9) mm, the length of screw trajectory on occipital side (occipital condyle-clivus) was (37.9±0.9) mm. Conclusion: The posterior atlantooccipital joint-occipital condyle-clivus screw technique can serve as a feasible and safe treatment for instability of the occipitocervical junction, which can be used as a new posterior occipitocervical fusion technique.

[Biomechanical study of anterior occipital condyle screw plate system].

Objective: To analyze the feasibility of anterior occipitocervical fusion biomechanical characteristic of craniovertebral reconstruction by anterior occipital condyle screw plate system. Methods: Six cervical vertebra specimens including 4 males and 2 females were enrolled, whose mean age of death was (49.3±7.5) years. The normal models were established by soft tissue dissection, and the instability models were established by destroy bone and ligament structure including, anterior arch of the atlas, part of the lateral mass of the atlas, the odontoid process, the odontoid apical ligament, the pterygoid ligament, the transverse ligament of the atlas the joint capsule. The clivus screw fixation models were established by anterior clivus screw fixation, and then those models were performed by anterior occipital condyle screw fixation. All four groups were loaded with a 1.5 N·m continuous pure force in flexion-extension, lateral bending, and axial rotation. Then measured the range of motion of specimen C0-C1 and C0-C2. And the pull-out force test was conducted to compare the effects of unicortical and bicortical fixation on the pull-out force of screws. Results: In the C0-C1 segment, the range of motion in flexion-extension (forward and posterior), lateral bending and axial rotation in the clivus group was 6.46°±0.85°, 5.14°±0.76°, 2.73°±0.36°, 1.12°±0.41°, respectively; and it was 5.92°±0.90°, 4.16°±1.06°, 2.86°±0.50°, 1.05°±0.27°, respectively in the occipital condyle group. As for C0-C2 segment, the range of motion in the clivus group was 9.55°±1.99°, 10.46°±2.03°, 6.90°±1.29°, 13.51°±1.37°, respectively; and it was 8.14°±1.38°, 9.53°±1.55°, 4.75°±1.06°, 7.90°±1.68°, respectively, in the occipital condyle group. The ranges of motion in the occipital condyle group were significantly lower than clivus group (all P<0.05). The maximum pull out force by bicortical fixation was significantly better than unicortical fixation ((439±33) N vs (408±28) N, P<0.05). Conclusion: The anterior occipital condyle screw plate system provides better stability especially in anti-bending and anti-rotation than the anterior clival screw fixation.

[Effects of anti-liver fibrosis treatment on the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis].

Objective: To investigate the effect of anti-liver fibrosis treatment on the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. Methods: 1,049 cases with hepatitis B-related liver cirrhosis who were hospitalized in Beijing Ditan Hospital affiliated to Capital Medical University from October 2008 to August 2016 were enrolled. Clinical data were collected, and COX regression analysis was used to find the independent influencing factors for the occurrence of liver cancer in patients with hepatitis B-related liver cirrhosis within three years. According to whether the patients had received anti-liver fibrosis treatment for ≥ 6 months, they were divided into combination and antiviral group. There were 388 cases in combination group and 661 cases in antiviral group. In addition, the combination group received anti-liver fibrosis therapy with Chinese patent medicine on the basis of antivirus, and the antiviral group received antiviral treatment. The incidence of liver cancer within three years were compared between the two groups, and the incidence of liver cancer in patients with different Child-Pugh grades and mPAGE-B risks was further analyzed. The independent samples t-test, Mann Whitney U test, χ2 test or Fisher's exact probability method were used for data comparison. Results: Anti-liver fibrosis treatment was an independent protective factor to prevent liver cancer in patients with hepatitis B-related liver cirrhosis within 3 years (P < 0.05). The incidence of liver cancer in the combination group was lower than antiviral group within 3 years (10.3% vs. 15.4%, χ (2) = 5.480, P < 0.05). Child-Pugh stratified analysis showed that the risk of liver cancer was significantly reduced in Child-Pugh grade A patients (6.7% vs. 12.6%, χ (2) = 2.857, P = 0.040). Among high-risk patients with mPAGE-B, the incidence of liver cancer was significantly lower in combination group than control group (13.7% vs. 19.9%, χ (2) = 6.671, P = 0.031). Conclusion: Compared to antiviral therapy alone, combined anti-liver fibrosis and antiviral therapy can reduce the liver cancer occurrence risk in patients with hepatitis B-related liver cirrhosis for 3 years. Patients with Child-Pugh grade A and high-risk group by mPAGE-B scores are the dominant population to receive treatment.

The Young-Laplace equation for a solid-liquid interface.

The application of the Young-Laplace equation to a solid-liquid interface is considered. Computer simulations show that the pressure inside a solid cluster of hard spheres is smaller than the external pressure of the liquid (both for small and large clusters). This would suggest a negative value for the interfacial free energy. We show that in a Gibbsian description of the thermodynamics of a curved solid-liquid interface in equilibrium, the choice of the thermodynamic (rather than mechanical) pressure is required, as suggested by Tolman for the liquid-gas scenario. With this definition, the interfacial free energy is positive, and the values obtained are in excellent agreement with previous results from nucleation studies. Although, for a curved fluid-fluid interface, there is no distinction between mechanical and thermal pressures (for a sufficiently large inner phase), in the solid-liquid interface, they do not coincide, as hypothesized by Gibbs.

Third-line treatment for metastatic colorectal cancer: anlotinib is superior to chemotherapy and similar to fruquintinib or regorafenib.

The clinical efficiency and adverse reactions of anlotinib in metastatic colorectal cancer (mCRC) as a third-line treatment compared with chemotherapy and regorafenib or fruquintinib was explored in this study. Clinical data from 105 mCRC patients who failed at least two lines of chemotherapy were collected. The patients were divided into three groups based on their third-line therapeutic regimen: third-line chemotherapy only (group A); anlotinib (group B); and fruquintinib or regorafenib (group C). The result showed that the ORR and DCR of group B (14.29%, 85.71%) were higher than those of group A (0%, 40.00%). The ORRs of group B and group C were 14.29% and 20.00%, respectively. Group B and group C had the same DCR, 85.71%. The mean PFS values of group B (3.46 months) and group C (3.33 months) were longer than that of group A (2.25 months) (χ2=84.255, p<0.001) and the mean PFS values of group B and group C were similar (χ2=0.884, p=0.347). The mean OS of group B was 9.22 months, which was longer than that of group A (6.95 months) (χ2=38.837, p<0.001). The mean OS values of group B (9.22 months) and group C (9.38 months) were not significantly different (χ2=0.456, p=0.499). The incidences of proteinuria, hand-foot skin reaction, myelosuppression, and gastrointestinal reaction were similar between group B and group C (p=0.173, 0.188, 1.00, 0.154, respectively). Myelosuppression and gastrointestinal reaction were more common in group A than in group B and group C (p<0.001). For mCRC, anlotinib as a third-line treatment is better than chemotherapy and similar to regorafenib or fruquintinib. The associated adverse reactions are tolerable.

[Clinical effect and economic benefit evaluation of minimally invasive surgery for drivers with lumbar disc herniation].

Objective: To investigate the clinical effect of minimally invasive surgery in the treatment of professional drivers with lumbar disc herniation. Methods: 126 patients with lumbar disc herniation admitted to hospital from June 1, 2015 to December 30, 2018 were selected and divided into observation group (59 cases treated by percutaneous transforaminal endoscopy) and control group (67 cases treated with conventional conservative treatment) according to the treatment methods. The Visual Analogue Scale (VAS) and Japanese Orthopaedic Association Scores (JOA) before and after treatment were analyzed retrospectively. Length of stay, time out of bed, hospitalization expenses and recurrence rate were evaluated. The measurement data was expressed by x±s, the comparison between groups was performed by t test, and the count data were analyzed by descriptive analysis. Results: Before treatment, there was no significant difference in gender, age, VAS score and JOA score between the two groups (P>0.05) . After treatment, compared with the control group, the VAS score of the observation group was lower, the JOA score was higher, the time out of bed was shorter, the average hospitalization time was reduced, the average hospitalization cost was higher, and the recurrence rates after Six months and one year were lower in the observation group, the differences were statistically significant (P<0.05) . Conclusion: The clinical effect of percutaneous transforaminal endoscopic treatment is better than that of conventional conservative treatment for driver＇s lumbar disc herniation.

Effects of jugular infusions of isoleucine, leucine, methionine, threonine, and other amino acids on insulin and glucagon concentrations, mammalian target of rapamycin (mTOR) signaling, and lactational performance in goats.

The supply and profile of absorbed AA may affect milk protein synthesis through hormonal changes and mammalian target of rapamycin (mTOR) signaling pathways; and Ile, Leu, Met, and Thr (ILMT) are the 4 AA that have been reported to have the greatest effect on mammary mTOR signaling. The extent to which ILMT and the other remaining AA (RAA) differ in their effects on milk protein synthesis needs to be systematically investigated. In this study, 5 lactating goats, averaging 120 ± 10 d in milk, fitted with jugular vein and carotid artery catheters, were fasted for 24 h, followed by intravenous infusions of a mixture containing AA and glucose for 8 h in a 5 × 5 Latin square design. The AA mixtures were formulated according to the profile of casein. The amounts of AA infused were calculated based on supplies of AA when metabolizable protein (MP) was at requirement (MR). Treatments were an infusate containing glucose without AA (NTAA); an infusate containing 3 × the MR of Ile, Leu, Met and Thr (3F0R); and infusates containing 3F0R plus 1, 2, or 3 × MR of RAA (3F1R, 3F2R, and 3F3R, respectively) according to amounts provided when fed to meet MP requirements for maintenance and lactation for each goat. Milk, arterial blood, and mammary tissue samples were collected immediately after halting the infusion. Relative to NTAA, supplementation of ILMT tended to increase milk protein production and plasma glucose concentrations, and increased milk and lactose production, but had no effects on production or content of milk fat. Graded supplementation of RAA tended to quadratically affect production of milk and lactose. Arterial glucose and glucagon concentrations decreased linearly, and plasma insulin concentrations decreased quadratically with increased RAA. Mammary p70-S6K1 phosphorylation was decreased by addition of ILMT compared with NTAA but increased linearly with increased RAA infusion. Furthermore, EIF4EBP1 gene expression was much lower for 3F-treated goats than for the NTAA treatment. Both MTOR and RPS6KB1 gene expressions were decreased quadratically with increased RAA supply. These results suggested that short-term milk protein yield tended to be increased by elevated ILMT availability, and this trend was not explained by variations in mammary mTOR signaling or pancreatic hormone secretions, whereas graded increase of RAA in combination with ILMT appeared to regulate the efficiency of conversion of glucose to lactose in a manner not involving milk protein production.

Effects of rumen-protected methionine and other essential amino acid supplementation on milk and milk component yields in lactating Holstein cows.

Objectives of this study were to investigate the effects of supplementing rumen-protected methionine (RP-Met), threonine (RP-Thr), isoleucine (RP-Ile), and leucine (RP-Leu) individually or jointly to a low-protein diet, on the performance of lactating dairy cows, as well as to determine the effects of these amino acids (AA) on the mammalian target of rapamycin (mTOR) in vivo. Ten lactating Holstein cows were randomly allocated to a repeated 5 × 5 Latin square experiment with five 19-d periods. Treatments were high-protein diet (16% crude protein, positive control; HP), low-protein diet (12% crude protein, negative control; LP), LP plus RP-Met (LPM), LP plus RP-Met and RP-Thr (LPMT), and LP plus RP-Met, RP-Thr, RP-Ile, and RP-Leu (LPMTIL). The dry matter intakes (DMI) of the LP, LPM, and LPMT diets were lower than that of the HP diet, whereas the DMI of the LPMTIL diet was intermediate between the HP diet and the other LP diets. Supplementing RP-Met to the LP diet increased the yields of milk and milk protein, increased the content of milk urea N, and tended to increase milk N efficiency. Co-supplementation of RP-Thr with RP-Met resulted in no further milk production increase. Co-supplementation of all 4 rumen-protected amino acids (RP-AA) increased milk and lactose yields to the level of the HP diet and tended to increase milk protein yield compared with the LPMT diet. We found no significant differences in the contents and yields of milk components between the LPMTIL and HP diets except for a lower milk urea N content in the LPMTIL diet. Venous concentrations of the measured AA were similar across the LP and LP diets supplemented with RP-AA. Relative to levels of the HP diet, LP diets had higher venous concentrations of Met and Gly and tended to have higher Phe concentration and lower concentrations of Val and BCAA. The LPMTIL diet had higher venous concentrations of Arg, Lys, Met, Phe, and Glu, and a lower Val concentration. Phosphorylation status of the measured mTOR components in LPM and LPMT treatments were similar to those in the LP treatment but phosphorylation status of mTOR and eIF4E-binding protein 1 (4eBP1) in LPMTIL treatment were higher. The phosphorylation rates of eukaryotic elongation factor 2 (eEF2) in the 4 LP and LP plus RP-AA diets were higher than that of the HP diet. Overall, results of the present study supported the concept that under the relatively short time of this experiment, supplementing RP-AA, which are believed to stimulate the mTOR signal pathway, can lead to increased milk protein yield. This increase appears to be due to increased DMI, greater mTOR signaling, and greater eEF2 activity.

[Mechanisms of fosfomycin resistance of extended-spectrum ß-lactamases-producing Escherichia coli and Klebsiella pneumoniae].

Objective: To study the in vitro activity of fosfomycin to extended-spectrum ß-lactamases (ESBLs)-producing Escherichia coli and Klebsiella pneumoniae and to explore the mechanisms of fosfomycin resistance. Methods: A total of 1 052 ESBLs-producing E. coli(ESBL-EC) and K. pneumoniae(ESBL-KP) isolates were collected from bloodstream infections of 28 hospitals of 22 provinces and municipalities, which were stored by our laboratory.Minimum inhibitory concentrations (MICs) of fosfomycin against these clinical isolates were determined by agar dilution methods according to the Clinical and Laboratory Standards Institute (CLSI)(2015). The genes related to fosfomycin resistance were confirmed by Polymerase Chain Reaction (PCR) and sequencing. Results: The susceptibility rates of ESBL-EC and ESBL-KP isolates to fosfomycin were 91.3% (818/896) and 91.7% (143/156), respectively. A total of 91 fosfomycin-non-susceptible isolates were detected, of which 73 (80.2%) isolates carried fosA3 genes.Amongst 18 fosA3-negative isolates, 16 isolates were detected to have chromosomal mutations or insertion inactivation, while the rest two isolates had not been detected any resistant mechanisms. Conclusions: Fosfomycin shows great in vitro antimicrobial activity to ESBL-EC and ESBL-KP. The primary mechanism of fosfomycin-non-susceptible isolates is fosA3 gene.Chromosomal mutations may also involve in the fosfomycin resistance.

Classification and regression tree analysis of acute-on-chronic hepatitis B liver failure: Seeing the forest for the trees.

At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBLF were screened in the study, which were recognized as derivation cohort and validation cohort, respectively. CART analysis was applied to predict the 3-month mortality of patients with ACHBLF. The accuracy of the CART model was tested using the area under the receiver operating characteristic curve, which was compared with the model for end-stage liver disease (MELD) score and a new logistic regression model. CART analysis identified four variables as prognostic factors of ACHBLF: total bilirubin, age, serum sodium and INR, and three distinct risk groups: low risk (4.2%), intermediate risk (30.2%-53.2%) and high risk (81.4%-96.9%). The new logistic regression model was constructed with four independent factors, including age, total bilirubin, serum sodium and prothrombin activity by multivariate logistic regression analysis. The performances of the CART model (0.896), similar to the logistic regression model (0.914, P=.382), exceeded that of MELD score (0.667, P<.001). The results were confirmed in the validation cohort. We have developed and validated a novel CART model superior to MELD for predicting three-month mortality of patients with ACHBLF. Thus, the CART model could facilitate medical decision-making and provide clinicians with a validated practical bedside tool for ACHBLF risk stratification.

Usefulness of albumin-bilirubin grade for evaluation of long-term prognosis for hepatitis B-related cirrhosis.

Long-term prognosis varies widely among patients with hepatitis B virus (HBV)-related liver cirrhosis. Our study aimed to investigate the applicability of albumin-bilirubin (ALBI), Child-Pugh and model for end-stage liver disease (MELD) scores to the long-term prognosis prediction of HBV-related cirrhosis. Patients diagnosed with HBV-associated cirrhosis from the First Affiliated Hospital of Wenzhou Medical University between January 2010 and December 2015 were enrolled in this study. The patients were followed up every 3 months. The prognostic performance of ALBI in long-term outcome prediction for HBV-related cirrhosis was compared with Child-Pugh and MELD scores using time-dependent receiver operating characteristic curve (tdROC) and decision curve analysis. A total of 806 patients were included in our study with 275 (34.1%) deceased during the follow-up. Multivariate Cox regression analysis showed that ALBI grade was an independent predictor associated with mortality. The tdROC analysis showed that ALBI score (0.787, 0.830 and 0.833) was superior to MELD (0.693, P=.003; 0.717, P<.001; 0.744, P<.001) and Child-Pugh score (0.641, P<.001; 0.649, P<.001; 0.657, P<.001) for predicting 1-year, 2-year and 3-year mortality. Additionally, decision curves also got the similar results. In addition, patients with lower ALBI score had a longer life expectancy, even among patients within the same Child-Pugh class. Thus, ALBI score was effective in predicting the long-term prognosis for patients with HBV-related cirrhosis and more accurate than Child-Pugh and MELD scores.

A diagnostic algorithm for assessment of liver fibrosis by liver stiffness measurement in patients with chronic hepatitis B.

Steatosis could affect liver stiffness measurement in patients with nonalcoholic fatty liver disease and chronic hepatitis C. In this study, we aimed to investigate the impact of steatosis on liver stiffness in hepatitis B virus (HBV)-infected patients and develop a diagnostic algorithm for prediction of liver fibrosis by liver stiffness based on the controlled attenuation parameter. A total of 488 HBV-infected patients who underwent clinical examination, Fibroscan and liver biopsy were prospectively enrolled. The best liver stiffness measurement (kPa) cut-offs for significant fibrosis (S≥3) and advanced fibrosis (S≥4) were 8.1 and 10.9, respectively. The best controlled attenuation parameter cut-off for severe steatosis (≥30%) was 287 dB/m. Among patients with low-grade fibrosis (S0-S2/S0-S3), mean liver stiffness values were significantly higher in subjects with severe steatosis or controlled attenuation parameter ≥287 dB/m compared with those without. Moreover, in subjects with low-grade fibrosis, a higher rate of false-positive rate was observed in patients with severe steatosis than those in patients without (F0-F2: 28.2% vs 9.7%; F0-F3: 17.0% vs 5.3%), and in patients with CAP≥287 dB/m compared with their counterpart (F0-F2: 23.7% vs 9.2%; F0-F3: 14.1% vs 4.8%). Low-grade fibrosis was accurately identified by γ-glutamyl transpeptidase-to-platelet ratio (GPR) with a cut-off value of 0.17. In patients with GPR<0.17, similar results were observed. The presence of steatosis may lead to overestimation of fibrosis assessed by liver stiffness measurement in patient with chronic hepatitis B. A diagnostic algorithm for assessing fibrosis using liver stiffness was developed by combining both controlled attenuation parameter and GPR values.

Preliminary evaluation of altered brain microstructure in the emotion-cognition region in children with haemophilia A: a diffusional kurtosis imaging study.

AIM: Using diffusional kurtosis imaging (DKI) to assess the impact of emotional disorders on microstructural changes of the brain in children with haemophilia A. MATERIALS AND METHODS: Diffusional kurtosis imaging was acquired from haemophilia A (n = 22) and controls (n = 22) using a 3T scanner. A regression analysis of frontal, cingulate, hippocampus, insula and amygdala regions of interest (ROIs) was conducted. Clinical data and results of psychological tests were collected. A paired t-test was used to analyse the differences between the two groups' ROIs, and the Spearman test was used to analyse the correlation between ROIs and psychological tests or clinical data. RESULTS: Fractional anisotropy (FA) in the left middle cingulate and right hippocampus; mean diffusion (MD) in the frontal lobe, right anterior cingulate and right middle cingulate showed varying degrees of increase in the ROI compared to controls (P < 0.003). MD in the frontal lobe and the course of disease (P < 0.05), FA in the right hippocampus and the social score of the self-consciousness scale (P < 0.01) had a positive correlation. CONCLUSION: Our study is the first to evaluate the relationship between emotion disorders and cognitive changes in the microstructure of the brain in children with haemophilia A, suggesting that DKI provides more information about tissue microstructural changes than do the conventional image method and traditional psychological tests.