[Endovascular therapy accompanied by spontaneous portosystemic shunts for overt hepatic encephalopathy].

Objective: To preliminarily evaluate the safety and efficacy of shunt-related interventional therapy accompanied with spontaneous portosystemic shunts (SPSS) in patients with hepatic encephalopathy (HE). Methods: Case data on six patients who underwent interventional therapy accompanied by SPSS for HE from January 2017 to March 2021 were collected to evaluate the efficacy and postoperative complications. Results: All six patients underwent SPSS. Four patients had hepatitis B cirrhosis; one had alcoholic cirrhosis; and one had hepatic arterioportal fistula-induced portal hypertension. Child-Pugh liver function scores were C and B in three and three cases, respectively. The SPSS type was gastrorenal shunt in two cases; portal-thoracic-azygos venous in two cases; portal-umbilical-iliac venous in one case; and portal-splenic venous - inferior vena cava in one case. Two of them had previously had a transjugular intrahepatic portosystemic shunt (TIPS), and there were SPSS prior to TIPS. Five cases (5/6) successfully underwent shunt embolization, and one case (1/6) underwent stent implantation for flow restriction (portal-umbilical-iliac vein). The technical success rate was 100%. HE did not recur during hospitalization or the three-month follow-up period. However, one case had a recurrence of HE within a year after surgery and was treated symptomatically, while another experienced gastrointestinal bleeding a year after surgery.. Conclusion: SPSS embolization or flow restriction is effective and safe for improving HE patients' symptoms.

[Analysis and forecast of burden of pancreatic cancer along with attributable risk factors in Asia countries between 1990 and 2019].

Objective: To analyze the disease burden of pancreatic cancer in major Asian countries and forecast the burden of that in China, which helps to provide reference for the prevention and control of pancreatic cancer. Methods: Data on disease burden of pancreatic cancer among global and major Asian countries from on the Global Burden of Disease (GBD) 2019 were collected to describe burden distribution through the absolute numbers or standardized rates of incidence, death and disability adjusted life years (DALY) by year, sex and socio-demographic index. Estimated annual percentage changes (EAPC) was used to assess the trend of standardized rate. The proportion of deaths attributable to risk factors for pancreatic cancer in 2019 was used to compare by age, sex and region. ARIMA model was performed with R language to predict change of age-standardized incidence and death rates of pancreatic cancer from 2020 to 2029. Results: From 1990 to 2019, the standardized incidence rates of pancreatic cancer in China increased from 3.17/100 000 to 5.78/100 000, and the standardized death rate increased from 3.34/100 000 to 5.99/100 000. The increases exceeded other high-income Asia countries. In the past three decades, the standardized incidence, death and DALY rates of pancreatic cancer in global have increased year by year. Among the major countries in Asia, China has the highest growth rate of disease burden (EAPC of standardized incidence rates=2.32%, 95% CI: 2.10%-2.48% and EAPC of standardized death rate=2.25%, 95% CI: 2.03%-2.42%). In addition, incidence and death rates of pancreatic cancer in China are expected to continue on the rise between 2000 and 2029 by ARIMA model. Incidence rate is expected to increase 15.92% and death rate is expected to increase 15.86%. Conclusions: The standardized incidence and death rates of pancreatic cancer in China increase year by year with an increasing trend for the burden of disease. The disease burden of pancreatic cancer is expected to rise due to the increase and aging of the population. Preventive measures should be adopted to decrease the burden of the pancreatic cancer.

Preventive effects of low molecular weight heparin on formation of deep vein thrombosis by reducing D dimer values in patients undergoing spinal surgery.

OBJECTIVE: Deep vein thrombosis (DVT) is one of the most common complications for patients undergoing spinal surgery. This study aims to investigate preventive effects of low-molecular-weight heparin (LMWH) on the formation of DVT. PATIENTS AND METHODS: This study involved 37 patients who underwent spinal surgery between April 2016 and April 2017. Patients were divided into LMWH group and Control group. Clinical parameters, including operation time, intra-operative blood loss, incision length, post-operative visual analogue scale (VAS), exercise-time leaving bed and post-operative extubation time, were collected. Blood routine analysis, including platelet count (PLT), red blood cell count (RBC), white blood cell count (WBC) and hemoglobin (HGB) were also conducted. Coagulation parameters, including prothrombin time-international normalized ratio (PT-INR), fibrinogen (FIB), activated partial thromboplastin time (APTT), thrombin time (TT), prothrombin time 1 (PT-1) and D-dimer (DD), were evaluated. The drainage fluid was collected. RESULTS: LMWH treatment significantly decreased operative time, blood loss and incision length compared to Control group at 1st, 3rd and 7th day post-operation (all p<0.05). LMWH treatment significantly increased WBC levels compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). LMWH treatment significantly decreased DD levels in the post-operative patients compared to Control group at 1st, 3rd and 7th day post-operation (p<0.05). However, LMWH treatment doesn't affect drainage amounts of patients. DD levels were positively correlated with WBC counts for the LMWH treated patients. CONCLUSIONS: Low molecular weight heparin effectively prevents the formation of DVT by reducing DD values in patients undergoing spinal surgery.

Genome-wide analysis of salinity-stress induced DNA methylation alterations in cotton (Gossypium hirsutum L.) using the Me-DIP sequencing technology.

Cytosine DNA methylation is a significant form of DNA modification closely associated with gene expression in eukaryotes, fungi, animals, and plants. Although the reference genomes of cotton (Gossypium hirsutum L.) have been publically available, the salinity-stress-induced DNA methylome alterations in cotton are not well understood. Here, we constructed a map of genome-wide DNA methylation characteristics of cotton leaves under salt stress using the methylated DNA immunoprecipitation sequencing method. The results showed that the methylation reads on chromosome 9 were most comparable with those on the other chromosomes, but the greatest changes occurred on chromosome 8 under salt stress. The DNA methylation pattern analysis indicated that a relatively higher methylation density was found in the upstream2k and downstream2k elements of the CDS region and CG-islands. Almost 94% of the reads belonged to LTR-gspsy and LTR-copia, and the number of methylation reads in LTR-gypsy was four times greater than that in LTR-copia in both control and stressed samples. The analysis of differentially methylated regions (DMRs) showed that the gene elements upstream2k, intron, and downstream2k were hypomethylated, but the CDS regions were hypermethylated. The GO (Gene Ontology) analysis suggested that the methylated genes were most enriched in cellular processes, metabolic processes, cell parts and catalytic activities, which might be closely correlated with response to NaCl stress. In this study, we completed a genomic DNA methylation profile and conducted a DMR analysis under salt stress, which provided valuable information for the better understanding of epigenetics in response to salt stress in cotton.

DEPDC5 mutations in familial and sporadic focal epilepsy.

BACKGROUND AND AIMS: Mutations in the disheveled, Egl-10 and pleckstrin domain-containing protein 5 (DEPDC5) gene have emerged as an important cause of various familial focal epilepsy syndromes. However, the significance of DEPDC5 mutations in patients with sporadic focal epilepsy has yet to be characterized. MATERIALS AND METHODS: We studied a kindred of familial focal epilepsy with variable foci using whole-exome sequencing. We subsequently studied a cohort of 293 patients with focal epilepsy and sequenced all exons of DEPDC5 using targeted resequencing. RESULTS: We reported a Taiwanese family with a novel splice site mutation which affected mRNA splicing and activated the downstream mammalian target of rapamycin (mTOR) pathway. Among patients with focal epilepsies, the majority (220/293) of these patients had sporadic focal epilepsy without malformation of cortical development. Two (0.9%) of these patients had probably pathogenic mutations in the DEPDC5 gene. DISCUSSION AND CONCLUSIONS: Our finding suggests that DEPDC5 is not only the most common gene for familial focal epilepsy but also could be a significant gene for sporadic focal epilepsy. Since focal epilepsies account for more than 60% of all epilepsies, the effect of mTORC1 inhibitor on patients with focal epilepsy due to DEPDC5 mutations will be an important future direction of research.

Effects of balanced selection for intramuscular fat and abdominal fat percentage and estimates of genetic parameters.

Intramuscular fat (IMF) content contributes to meat flavor and improves meat quality. Excessive abdominal fat, however, leads to a waste of feed resources. Here, an independent up-selection for IMF was used as a control (Line C), and a balanced selection program, with up-selection for IMF and down-selection AFP (Line B), was studied in JingXing yellow chickens. The mean of IMF and AFP within a family was the phenotypic value upon which selection was based. The selective pressures of IMF in line B and line C were the same in each generation. At G5, the IMF was significantly higher (P < 0.05) than that at G0 in both lines. For AFP, Line C was significantly higher at G5 (P < 0.05) than at G0, but the difference in Line B was not significant (P > 0.05). IMF increased by 11.4% and AFP decreased by 1.5% in Line B compared with the G0 generation. In contrast, the IMF increased by 17.6%, but was accompanied by an 18.7% increase in AFP, in control Line C. Of 10 other traits measured, body weight at 56 d age (BW56) and the percentages of eviscerated weight (EWP) showed a significant difference between the 2 lines (P < 0.05). The heritabilities for IMF and AFP, estimated by the DMU package, were 0.16 and 0.32, respectively. A moderate positive correlation existed between IMF and AFP (0.35). A balanced selection program for increasing IMF while controlling AFP (Line B) is shown here to be effective in practical chicken breeding.

[Mutation analysis of GJB2 gene in 1 822 patients with nonsyndromic hearing loss in Zhejiang Province].

Objective:To analyze the genetic characteristics in nonsyndromic hearing impairment (NSHL) patients in Zhejiang province.Method:Peripheral blood samples were obtained from 1822 NSHL patients and 467 normal hearing controls in Zhejiang province. We carried out a systematic mutational screening of GJB2 gene in these subjects by amplifying the coding region of GJB2 gene and sequencing directly.Result:Thirty kinds of mutation were identified, including eleven pathogenic mutations, one hypomorphic allele, sixteen polymorphic mutations and two novel mutations. The c.235delC mutation was the most prevalent pathogenic mutation in this cohort (18.50%), and the rate of allele mutation was 12.16%. The frequency of c.299_300delAT,c.176_191del16,c.512_513insAACG,c.35delG,c.283G>A,c.427C>T,c.35insG,c.439G>A,c.571T>C,c.139G>T mutations were decreased in turn.Conclusion:c.235delC mutation is the hot spot of GJB2 gene mutation in NSHL patients in Zhejiang province and the most common mutational pattern is frame-shift mutation. The discovery of novel mutations enriches the spectrum and frequency of variants in GJB2 gene.

Genome-wide identification and expression analysis of CIPK genes in diploid cottons.

Calcineurin B-like protein-interacting protein kinase (CIPK) plays a key regulatory role in the growth, development, and stress resistance of plants by combining with phosphatase B subunit-like protein. In the present study, CIPK genes were identified in the whole genomes of diploid cottons and their sequences were subjected to bioinformatic analyses. The results demonstrated that the CIPK gene family was unevenly distributed in two diploid cotton genomes. Forty-one CIPKs were identified in the D genome, mainly located on chromosomes 9 and 10, whereas thirty-nine CIPKs were identified in the A genome, mainly located on chromosomes 8 and 11. Based on the gene structures, CIPKs in cotton could be classified into two types: one that is intron-rich and the other that has few introns. Phylogenetic analysis revealed that the CIPK gene family members in cotton had close evolutionary relationships with those of the dicotyledonous plants, such as Arabidopsis thaliana and poplar. The analysis of transcriptome sequence data demonstrated that there were differences in gene expression in different tissues, indicating that the expression of the CIPKs in cotton had spatio-temporal specificity. The expression analysis of CIPKs under abiotic stresses (drought, salt, and low temperature) in different tissues at trefoil stage demonstrated that these stresses induced the expression of CIPKs.

Magnesium activated adenosine formation in intact perfused heart: predominance of ecto 5'-nucleotidase during hypermagnesemia.

Magnesium ion is an allosteric effector of 5'-nucleotidase and thus activates adenosine production from AMP. Two distinct 5'-nucleotidase systems, the membrane-bound ecto and the soluble cytosolic isoforms, exist in mammalian myocardium. The aim of this study was to delineate the contributions of the ecto vs. cytosolic isoforms to Mg2+-stimulated cardiac purine nucleoside formation and release. Isolated guinea pig hearts were retrogradely perfused at their physiological aortic pressure with Krebs-Henseleit bicarbonate buffer fortified with 10 mM glucose. AMP and the adenylate degradatives adenosine and inosine were measured in coronary venous effluent and in epicardial transudate, which was sampled to estimate concentrations of adenylate degradatives in the interstitium. When perfusate Mg2+ was increased from 0.6 to 6 mM, coronary vascular resistance and spontaneous heart rate fell, and steady-state coronary venous release of adenosine + inosine rose severalfold. Cytosolic free magnesium, as estimated by 31P-NMR after 15 min of perfusion with 6 mM Mg2+ or from chemically measured indicator metabolites after 30 min, rose 60 and 144% respectively (P < 0.05). Excess Mg2+ stimulated purine nucleoside release nearly threefold in coronary venous effluent and four- to sevenfold in epicardial transudate. 50 microM, alpha,beta-methylene adenosine 5'-diphosphate (AOPCP), a selective inhibitor of ecto 5'-nucleotidase, elevated interstitial AMP concentration tenfold, did not attenuate basal nucleoside release, but completely inhibited Mg2+-stimulated coronary venous purine nucleoside release and blunted Mg2+-stimulated interstitial purine nucleoside formation by 69%. During perfusion with exogenous 1 microM [8-14C]AMP, excess perfusate MgCl2 increased [14C]adenosine release by 63% in coronary effluent and 133% in epicardial transudate. AOPCP decreased baseline [14C]adenosine release in coronary effluent and epicardial transudate by 85-90%, caused equilibration of arterial and epicardial AMP, and attenuated MgCl2 activation of p[14C]adenosine formation by approx. 75%, in both the vascular and interstitial compartments. Intramyocytic concentrations of allosteric regulators of the cytosolic 5'-nucleotidases were evaluated in stop-frozen myocardium. Excess magnesium did not appreciably alter intracellular pH and ATP concentration, but lowered free cytosolic ADP and AMP concentrations by 50 and 70%, respectively. A simplified model of compartmentalized adenosine metabolism is proposed in which magnesium ion-activated cardiac purine release originates predominantly from the ecto 5'-nucleotidase; magnesium ion stimulation of metabolic flux through the cytosolic isoforms was constrained by concomitant reductions in intracellular AMP substrate and allosteric activator ADP. Magnesium ion-enhanced adenosine formation by 5'-nucleotidase could contribute to the known cardioprotective effects of this clinically used cation.

Does interstitial adenosine mediate acute hibernation of guinea pig myocardium?

OBJECTIVE: The aim was to test the role of interstitial adenosine in protective downregulation of myocardial energy demand during myocardial hibernation. METHODS: Isolated working guinea pig hearts, perfused with glucose fortified Krebs-Henseleit, were subjected to 60 min global low flow ischaemia followed by 30 min reperfusion. Left ventricular performance was assessed from heart rate-developed pressure product and pressure-volume work. Cytosolic energy level was indexed by creatine phosphate and ATP phosphorylation potentials measured in snap frozen myocardium. Lactate and purine nucleosides (adenosine, inosine) were measured in venous effluent. RESULTS: When coronary flow was lowered by 80% for 60 min, heart rate-pressure product and pressure-volume work fell 87% and 75%, respectively, and stabilised at these low levels, but fully recovered when flow was restored. Myocardial ATP phosphorylation potential fell by 67% during the first 10 min of ischaemia, but subsequently recovered to preischaemic levels despite continuing ischaemia, indicating down-regulation of myocardial energy demand. Lactate release increased about 10-fold during ischaemia and remained increased until reperfusion. Purine nucleoside release varied reciprocally with phosphorylation potential, peaking at 10 min of ischaemia, then gradually returning to the preischaemic level during the subsequent 50 min of ischaemia. The ecto 5'-nucleotidase inhibitor alpha,beta-methylene adenosine 5'-diphosphonate (50 microM) decreased ischaemic purine nucleoside release by 41%, but did not attenuate postischaemic contractile recovery. The unspecific adenosine receptor antagonist 8-p-sulphophenyl theophylline (8-SPT, 20 microM) doubled ischaemic lactate release and lowered coronary venous purine nucleoside release by 21%. 8-SPT increased phosphorylation potential at 10 min ischaemia relative to untreated hearts, but blunted the subsequent rebound of phosphorylation potential. 8-SPT treatment during ischaemia resulted in a significantly higher cytosolic phosphorylation potential at 30 min of reperfusion, but did not affect postischaemic contractile function. CONCLUSIONS: We conclude that activation of adenosine receptors results in recovery of cytosolic energy level of moderately ischaemic working myocardium, but this energetic recovery is not solely responsible for postischaemic contractile recovery.

Coronary pressure-flow autoregulation protects myocardium from pressure-induced changes in oxygen consumption.

Pressure-flow autoregulation minimizes changes in coronary blood flow (CBF) when coronary perfusion pressure (CPP) is altered. This investigation determined if autoregulation also minimizes CPP-induced changes in coronary vascular volume (CVV) and CVV-dependent changes in myocardial oxygen consumption (MVO2). In 11 anesthetized dogs, the left anterior descending coronary artery was cannulated, and responses to 20-mmHg changes in CPP were examined over a range of CPP from 60 to 180 mmHg. Changes in CPP had no significant effect on systemic hemodynamics or on left ventricular end-diastolic segment length, end-systolic segment length, or percent segment shortening. In hearts with effective pressure-flow autoregulation [closed-loop gain (GC) > 0.4], CVV increased 0.06%/mmHg change in CPP. For the same hearts, MVO2 increased 0.04%/mmHg change in CPP. In hearts with ineffective autoregulation (GC < 0.4), CVV increased 0.97%/mmHg (P < 0.001 vs. autoregulating hearts), and MVO2 increased 0.41%/mmHg (P < 0.001 vs. autoregulating hearts). MVO2 and CVV were correlated (r = 0.69, P < 0.0001) independently of autoregulatory capability, but only when autoregulation was poor and capacitance was elevated did CPP significantly affect MVO2. We conclude that pressure-flow autoregulation protects myocardium from CPP-induced changes in CVV, which in turn produces changes in oxygen consumption.

Effects of snuff on regional blood flow to the cheek and tongue of anesthetized dogs.

Regional blood flow to the cheek and tongue of anesthetized dogs was measured before and after application of six different doses of snuff (3.12 to 100 mg/kg body weight) to the right cheek. Dose-independent vasodilation was observed at the site of application, whereas dose-dependent vasoconstriction was observed contralaterally. Aortic, central venous, and ventricular pressures were significantly increased (p < 0.05) at the higher doses. Plasma nicotine concentrations increased stepwise with dose.

Acute normovolemic hemodilution in coronary artery bypass graft surgery.

Twenty patients undergoing coronary artery bypass graft (CABG) surgery in April through May, 1990 in our hospital were included in this study to evaluate the merits and practicability of autologous blood transfusion. About 1,000 ml of arterial blood were collected via a radial arterial line and stored in a plastic bag containing CPD solution immediately after induction of anesthesia. Colloid or crystalloid solution was used to replace the volume deficit after the blood sampling. At the end of cardiopulmonary bypass and after adequate reversal of heparinization by protamine, the blood previously sampled was re-transfused to the patient via a peripheral venous line. Thirty patients undergoing CABG surgery, who did not receive autologous blood transfusion from February to June, 1990 save April and May were assigned as control. Comparison of the data between the two groups was made using the Student's t-test. It was found that the intraoperative acute normovolemic hemodilution could lower the hematocrit by approximately 12%. Packed red blood cells (PRBC) given intraoperatively in the autologous group was only 2.0 +/- 0.4 units whereas it was 5.3 +/- 0.7 units in the control group (p less than 0.001). Fresh frozen plasma (FFP) given intraoperatively in the autologous group was only 1.8 +/- 0.5 units whereas it was 6.6 +/- 0.7 units in the control group (p less than 0.001). The amount of platelets given intraoperatively in the autologous group was 1.9 +/- 1.0 units against 9.3 +/- 1.4 units in the control group (p less than 0.001). Thus, acute normovolemic hemodilution in CABG surgery decreased intraoperative requirement of bank blood components including PRBC, FFP and platelets.(ABSTRACT TRUNCATED AT 250 WORDS)