Postoperative complications and short-term prognosis of laparoscopic pancreaticoduodenectomy vs. open pancreaticoduodenectomy for treating pancreatic ductal adenocarcinoma: a retrospective cohort study.

BACKGROUND: Although laparoscopic pancreaticoduodenectomy (LPD) has been accepted worldwide for treating pancreatic ductal adenocarcinoma (PDA), it is a very technical and challenging procedure. Also, it is unclear whether LPD is superior to open pancreaticoduodenectomy (OPD). This study summarized the experience and efficacy of LPD for treating PDA in our medical center. METHODS: This retrospective cohort study included patients with PDA admitted at the Affiliated Hospital of Jiangnan University from October 2019 and January 2021. Patients received either LPD or OPD. Clinical outcomes (operation time, duration of anesthesia, intraoperative hemorrhage), postoperative complications, and short-term outcomes were compared. Cox proportional hazard model and Kaplan-Meier method were used to analyze overall survival (OS) and progression-free survival (PFS). RESULTS: Among the PDA patients, 101 patients underwent surgical treatment, 4 patients converted from LPD to OPD, and 7 of them received conservative treatment. Forty-six patients were cured of LPD, and 1 of them died shortly after the operation. Moreover, 44 patients received OPD, and there were 2 postoperative deaths. There were significant differences in the location of the operation time, duration of anesthesia, postoperative hemorrhage, abdominal infections, and postoperative pneumonia between the two groups (all p < 0.05). Multivariate analysis showed that LPD was an independent factor negatively correlated with the incidence of pneumonia (relative risk (RR) = 0.072, 95%CI: 0.016-0.326, p = 0.001) and abdominal infection (RR = 0.182, 95%CI: 0.047-0.709, p = 0.014). Also, there were no differences in OS (hazard ratio (HR) = 1.46, 95%CI: 0.60-3.53, p = 0.40) and PFS (HR = 1.46, 95%CI: 0.64-3.32, p = 0.37) at 12 months between the two groups. CONCLUSIONS: LPD could be efficacy and feasible for managing selected PDA patients. Also, LPD has a better effect in reducing postoperative pneumonia and abdominal infection compared to OPD.

Mapping of a QTL with major effect on reducing leaf rust severity at the adult plant growth stage on chromosome 2BL in wheat landrace Hongmazha.

KEY MESSAGE: A major QTL (QLr.cau-2BL) for APR to leaf rust was detected on 2BL; an SSR marker was developed to closely link with QLr.cau-2BL and validated for effectiveness of MAS. The wheat landrace Hongmazha (HMZ) possesses adult plant resistance (APR) to leaf rust. To detect and validate quantitative trait locus (QTL) for the APR, four wheat populations were assessed for leaf rust severity in a total of eight field and greenhouse experiments. The mapping population Aquileja × HMZ (120 recombinant inbred lines, RILs) was genotyped using 90 K SNP markers. A major QTL (QLr.cau-2BL) was detected between the markers IWB3854 and IWB21922 on chromosome 2BL. IWB3854 and IWB21922 were positioned at approximately 531.14 Mb and 616.48 Mb, respectively, on 2BL of IWGSC RefSeq v1.0 physical map. Based on the sequences between 531.14 and 616.48 Mb on 2BL of IWGSC RefSeq v1.0, 415 simple sequence repeat (SSR) markers were developed. These markers and 28 previously published SSR makers were screened; the resulted polymorphic markers were used to genotype the relatively larger population RL6058 × HMZ (371 RILs). QLr.cau-2BL was mapped within a 1.5 cM interval on 2BL map of RL6058 × HMZ, and a marker (Ta2BL_ssr7) was identified to closely link with QLr.cau-2BL. Effectiveness of selection for QLr.cau-2BL based on Ta2BL_ssr7 was validated using two populations (RL6058 × HMZ F2:3 and Jimai22 × HMZ BC4F2:3). In addition, polymorphism at Ta2BL_ssr7 was detected among a panel of 282 commercial wheat cultivars. We believe, therefore, that Ta2BL_ssr7 should be useful for introducing QLr.cau-2BL into commercial wheat cultivars and for accumulating QLr.cau-2BL with other APR QTL.

Activation of SIRT1 by Resveratrol Alleviates Pressure Overload-Induced Cardiac Hypertrophy via Suppression of TGF-ß1 Signaling.

INTRODUCTION: Silent information regulator 1 (SIRT1) has been extensively investigated in the cardiovascular system and has been shown to play a pivotal role in mediating cell death/survival, energy production, and oxidative stress. However, the functional role of SIRT1 in pressure overload-induced cardiac hypertrophy and dysfunction remains unclear. Resveratrol (Rsv), a widely used activator of SIRT1, has been reported to protect against cardiovascular disease. We here examine whether activation of SIRT1 by Rsv attenuate pressure overload-induced cardiac hypertrophy and to identify the underlying molecular mechanisms. METHODS: In vivo, rat model of pressure overload-induced myocardial hypertrophy was established by abdominal aorta constriction (AAC) procedure. In vitro, Angiotensin II (Ang II) was applied to induce hypertrophy in cultured neonatal rat cardiomyocytes (NCMs). Hemodynamics and histological analyses of the heart were evaluated. The expression of SIRT1, transforming growth factor-ß1 (TGF-ß1)/phosphorylated (p)-small mother against decapentaplegic (Smad)3 and hypertrophic markers were determined by immunofluorescence, real-time PCR, and Western blotting techniques. RESULTS: In the current study, Rsv treatment improved left ventricular function and reduced left ventricular hypertrophy and cardiac fibrosis significantly in the pressure overload rats. The expression of SIRT1 was significantly reduced, while the expression of TGF-ß1/p-Smad3 was significantly enhanced in AAC afflicted rat heart. Strikingly, treatment with Rsv restored the expressions of SIRT1 and TGF-ß1/p-Smad3 under AAC influence. However, SIRT1 inhibitor Sirtinol (Snl) markedly prevented the effects of Rsv, which suggest that SIRT1 signaling pathway was involved in the cardiac protective effect of Rsv. In vitro studies performed in Ang II-induced hypertrophy in NCMs confirmed the cardiac protective effect of Rsv. Furthermore, the study presented that SIRT1 negatively correlated with the cardiac hypertrophy, cardiac fibrosis, and the TGF-ß1/p-Smad3 expression. CONCLUSIONS: Taken together, these results indicated that activation of SIRT1 by Rsv attenuates cardiac hypertrophy, cardiac fibrosis, and improves cardiac function possibly via regulation of the TGF-ß1/p-Smad3 signaling pathway. Our study may provide a potential therapeutic strategy for cardiac hypertrophy.

Diabetes aggravates myocardial ischaemia reperfusion injury via activating Nox2-related programmed cell death in an AMPK-dependent manner.

Cardiovascular diseases such as myocardial ischaemia have a high fatality rate in patients with diabetes. This study was designed to expose the crosstalk between oxidative stress and AMPK, a vital molecule that controls biological energy metabolism, in myocardial ischaemia reperfusion injury (I/RI) in diabetic rats. Diabetes was stimulated in rats using streptozotocin injection. Rats were separated on random into control, control + I/R, Diabetes, Diabetes + I/R, Diabetes + I/R + N-acetylcysteine and Diabetes + I/R + Vas2870 groups. Myocardial infarct size was determined, and the predominant Nox family isoforms were analysed. In vitro, the H9C2 cells were administered excess glucose and exposed to hypoxia/reoxygenation to mimic diabetes and I/R. The AMPK siRNA or AICAR was used to inhibit or activate AMPK expression in H9C2 cells, respectively. Then, myocardial oxidative stress and programmed cell death were measured. Diabetes or high glucose levels were found to aggravate myocardial I/RI or hypoxia/reoxygenation in H9C2 cells, as demonstrated by an increase in myocardial infarct size or lactate dehydrogenase levels, oxidative stress generation and induction of programmed cell death. In diabetic rat hearts, cardiac Nox1, Nox2 and Nox4 were all heightened. The suppression of Nox2 expression using Vas2870 or Nox2-siRNA treatment in vivo or in vitro, respectively, protected diabetic rats from myocardial I/RI. AMPK gene knockout increased Nox2 protein expression while AMPK agonist decreased Nox2 expression. Therefore, diabetes aggravates myocardial I/RI by generating of Nox2-associated oxidative stress in an AMPK-dependent manner, which led to the induction of programmed cell death such as apoptosis, pyroptosis and ferroptosis.

Acid-sensing Ion Channel 3 Overexpression in Incisions Regulated by Nerve Growth Factor Participates in Postoperative Nociception in Rats.

BACKGROUND: Acid-sensing ion channel 3 (ASIC3) upregulation has been reported in dorsal root ganglion neurons after incision and contributes to postoperative nociception. This study hypothesized that upregulation of ASIC3 in incised tissues is induced by nerve growth factor through the phosphoinositide 3-kinase/protein kinase B signaling pathway. METHODS: A plantar incision model was established in adult male and female Sprague-Dawley rats. ASIC3 was inhibited by APETx2 treatment, small interfering RNA treatment, or ASIC3 knockout. Sciatic nerve ligation was performed to analyze ASIC3 transport. A nerve growth factor antibody and a phosphoinositide 3-kinase inhibitor were used to investigate the mechanism by which nerve growth factor regulates ASIC3 expression. RESULTS: Acid-sensing ion channel 3 inhibition decreased incisional guarding and mechanical nociception. ASIC3 protein levels were increased in skin and muscle 4 h after incision (mean ± SD: 5.4 ± 3.2-fold in skin, n = 6, P = 0.001; 4.3 ± 2.2-fold in muscle, n = 6, P = 0.001). Sciatic nerve ligation revealed bidirectional ASIC3 transport. Nerve growth factor antibody treatment inhibited the expression of ASIC3 (mean ± SD: antibody 2.3 ± 0.8-fold vs. vehicle 4.9 ± 2.4-fold, n = 6, P = 0.036) and phosphorylated protein kinase B (mean ± SD: antibody 0.8 ± 0.3-fold vs. vehicle 1.8 ± 0.8-fold, n = 6, P = 0.010) in incised tissues. Intraplantar injection of nerve growth factor increased the expression of ASIC3 and phosphorylated protein kinase B. ASIC3 expression and incisional pain-related behaviors were inhibited by pretreatment with the phosphoinositide 3-kinase inhibitor LY294002. CONCLUSIONS: Acid-sensing ion channel 3 overexpression in incisions contributes to postoperative guarding and mechanical nociception. Bidirectional transport of ASIC3 between incised tissues and dorsal root ganglion neurons occurs through the sciatic nerve. Nerve growth factor regulates ASIC3 expression after plantar incision through the phosphoinositide 3-kinase/protein kinase B signaling pathway.

Dexmedetomidine alleviates H2O2-induced oxidative stress and cell necroptosis through activating of α2-adrenoceptor in H9C2 cells.

Oxidative stress induced necroptosis is important in myocardial ischemia/reperfusion injury. Dexmedetomidine (Dex), an α2-adrenoceptor (α2-AR) agonist, has protective effect on oxidative stress induced cell apoptosis, but effects of Dex and Dex-mediated α2-AR activation on oxidant induced necroptosis was unclear. H9C2 cardiomyocytes were pre-treated with or without Dex and α2-AR antagonist yohimbine hydrochloride (YOH) before being exposed to H2O2 to induce oxidative cellular damage. Cell viability and lactate dehydrogenase (LDH) were detected by ELISA kits, protein expressions of Heme Oxygenase 1(HO-1), receptor interacting protein kinase 1 (RIPK1) and receptor interacting protein kinase 3 (RIPK3) were observed by WB, and TUNEL was used to detected cell apoptosis. H2O2 significantly decreased cell viability and increased LDH release and necroptotic and apoptotic cell deaths (all p < 0.05, H2O2 vs. Control). Dex preconditioning alleviated these injuries induced by H2O2. Dex preconditioning significantly increased expression of protein HO-1 and decreased expressions of proteins RIPK1 and RIPK3 induced by H2O2, while all these protective effects of Dex were reversed by YOH (all p < 0.05, Dex + H2O2 vs. H2O2; and YOH + Dex + H2O2 vs. Dex + H2O2). However, YOH did not prevent this protective effect of Dex against H2O2 induced apoptosis (YOH + Dex + H2O2 vs. Dex + H2O2, p > 0.05). These findings indicated that Dex attenuates H2O2 induced cardiomyocyte necroptotic and apoptotic cell death respectively dependently and independently of α2-AR activation.

Identification of a major QTL on chromosome arm 2AL for reducing yellow rust severity from a Chinese wheat landrace with evidence for durable resistance.

KEY MESSAGE: A QTL on 2AL for reducing yellow rust severity was identified from a Chinese wheat landrace, being more effective than Yr18, with evidence for durable resistance from field observations. Utilization of wheat resistance is an important strategy to control yellow rust. The Chinese wheat landrace Hong Qimai (HQM) and the advanced breeding line AQ24788-83 (AQ; a progeny of HQM) can significantly reduce disease severity at the adult-plant growth stage. HQM has maintained adult-plant resistance for a prolonged period of time. To study the inheritance of the resistance, 126 recombinant inbred lines (RILs) derived from the cross Thatcher (TC) × HQM and 138 RILs from Luke × AQ were assessed for disease severity in six field trials. A genetic map of TC × HQM was constructed by genotyping these RILs using the 90 K wheat single-nucleotide polymorphism chip. Luke × AQ map was previously constructed for another disease study and also utilized here. Based on these maps and disease data, a quantitative trait locus (QTL) was detected on the chromosome arm 2AL from both TC × HQM and Luke × AQ and designated as QYr.cau-2AL. The resistance allele at QYr.cau-2AL came from HQM and AQ. QYr.cau-2AL was significantly effective across all the test environments and different genetic backgrounds, with its effect magnitude being higher than that of Yr18. QYr.cau-2AL synergistically acted with Yr18 and a QTL for high-temperature adult-plant resistance on 2BS, resulting in an elevated resistance from the juvenile plant growth stage onward, although QYr.cau-2AL alone displayed no substantial resistance at juvenile stage. Evidence indicates that QYr.cau-2AL is novel and confers durable resistance, and thus, should have high potential value for practical breeding.

Detection and validation of a novel major QTL for resistance to Fusarium head blight from Triticum aestivum in the terminal region of chromosome 7DL.

KEY MESSAGE: A novel QTL for FHB resistance was mapped on wheat 7DL, being effective in multiple genetic backgrounds and environments, and comparable to Fhb1 in effect magnitude. Fusarium head blight (FHB) is one of the major fungal diseases affecting wheat production in many countries. The wheat line AQ24788-83 (AQ) possesses FHB resistance. The American wheat cultivar Luke is FHB susceptible. A Luke × AQ population consisting of 1652 advanced recombinant inbred lines (RILs) was developed, from which 272 RILs were randomly sampled and used to construct a linkage map. Another 154 RILs were selected for homogeneity in plant height (PH) and flowering date (FD). This selection strategy was adopted to reduce possible confounding effects on FHB assessment due to variation in PH and FD. The 272 and 154 RILs were genotyped applying simple sequence repeat (SSR), diversity arrays technology (DArT) and single-nucleotide polymorphism (SNP) markers. The two sets of RILs were evaluated for FHB resistance applying point inoculation in greenhouses; the 154 RILs were also evaluated applying spray inoculation in multiple field environments. The linkage map consisted of 2088 SSR, DArT, and SNP markers. A FHB resistance quantitative trait locus (QTL), designated as QFhb.cau-7DL, was detected on chromosome arm 7DL; this QTL was closely linked to the SSR marker gwm428 ( http://www.wheat.pw.usda.gov/ggpages/SSR/ ). QFhb.cau-7DL was significantly effective (α = 0.01) in every test trial, and its effectiveness was validated using three additional wheat crosses. Sumai 3 (donor wheat of the FHB resistance gene Fhb1) was used in one of these crosses. QFhb.cau-7DL was comparable to Fhb1 in effect magnitude, providing a great potential for improving FHB resistance.

Fine mapping of the wheat powdery mildew resistance gene Pm52 using comparative genomics analysis and the Chinese Spring reference genomic sequence.

KEY MESSAGE: A high-resolution genetic linkage map was constructed using the comparative genomics analysis approach and the wheat reference genome, which placed wheat powdery mildew resistance gene Pm52 in a 0.21-cM genetic interval on chromosome arm 2BL. The gene Pm52 confers resistance to powdery mildew and has been previously mapped on chromosome arm 2BL in winter wheat cultivar Liangxing 99. Because of its effectiveness against the disease, this study was initiated to finely map Pm52 using the comparative genomics analysis approach and the wheat reference genomic sequence. Based on the EST sequences that were located in the chromosome region flanking Pm52, four EST-SSR markers were developed, and another nine SSR markers were developed using the comparative genomics technology. These thirteen markers were integrated into a genetic linkage map using an F2:3 subpopulation of the Liangxing 99 × Zhongzuo 9504 cross. Pm52 was mapped within a 3.2-cM genetic interval in the subpopulation that corresponded to a ~40-Mb genomic interval on chromosome arm 2BL of the Chinese Spring reference genome. The Pm52-flanking markers Xicsl163 and Xicsl62 identified 344 recombinant individuals from 8820 F2 plants. Nine SSR markers generated from the Chinese Spring genomic interval were incorporated into a high-resolution genetic linkage map, which placed Pm52 in a 0.21-cM genetic interval corresponding to 5.6-Mb genomic region. The constructed high-resolution genetic linkage map will facilitate the map-based cloning of Pm52 and its marker-assisted selection.

N-Acetylcysteine Attenuates Diabetic Myocardial Ischemia Reperfusion Injury through Inhibiting Excessive Autophagy.

Background. Excessive autophagy is a major mechanism of myocardial ischemia reperfusion injury (I/RI) in diabetes with enhanced oxidative stress. Antioxidant N-acetylcysteine (NAC) reduces myocardial I/RI. It is unknown if inhibition of autophagy may represent a mechanism whereby NAC confers cardioprotection in diabetes. Methods and Results. Diabetes was induced in Sprague-Dawley rats with streptozotocin and they were treated without or with NAC (1.5 g/kg/day) for four weeks before being subjected to 30-minute coronary occlusion and 2-hour reperfusion. The results showed that cardiac levels of 15-F2t-Isoprostane were increased and that autophagy was evidenced as increases in ratio of LC3 II/I and protein P62 and AMPK and mTOR expressions were significantly increased in diabetic compared to nondiabetic rats, concomitant with increased postischemic myocardial infarct size and CK-MB release but decreased Akt and eNOS activation. Diabetes was also associated with increased postischemic apoptotic cell death manifested as increases in TUNEL positive cells, cleaved-caspase-3, and ratio of Bax/Bcl-2 protein expression. NAC significantly attenuated I/RI-induced increases in oxidative stress and cardiac apoptosis, prevented postischemic autophagy formation in diabetes, and reduced postischemic myocardial infarction (all p < 0.05). Conclusions. NAC confers cardioprotection against diabetic heart I/RI primarily through inhibiting excessive autophagy which might be a major mechanism why diabetic hearts are less tolerant to I/RI.

A QTL with major effect on reducing leaf rust severity on the short arm of chromosome 1A of wheat detected across different genetic backgrounds and diverse environments.

KEY MESSAGE: Selection for QLr.cau - 1AS (a major QTL detected in wheat for reducing leaf rust severity) based on the DNA marker gpw2246 was as effective as selection for Lr34 based on cssfr5. Leaf rust is an important disease of wheat worldwide. Utilization of slow-rusting resistance constitutes a strategy to sustainably control this disease. The American wheat cultivar Luke exhibits slow leaf-rusting resistance at the adult plant stage. The objectives of this study were to detect and validate QTL for the resistance in Luke. Three winter wheat populations were used, namely, 149 recombinant inbred lines (RILs) derived from the cross Luke × Aquileja, 307 RILs from Luke × AQ24788-83, and 80 F2:3 families selected from Lingxing66 × KA298. Aquileja and Lingxing66 are highly susceptible to leaf rust. AQ24788-83 shows high (susceptible) infection type but contains the slow-rusting gene Lr34 as diagnosed by the gene-specific marker cssfr5. KA298, an F9 RIL selected from Luke × AQ24788-83, contains Lr34 and QLr.cau-1AS (a major QTL originated from Luke, this study). These wheats were evaluated for leaf rust in 12 field and greenhouse environments involving four locations and five seasons. Genotyping was done using simple sequence repeat (SSR) and diversity arrays technology markers. Of the detected QTLs, QLr.cau-1AS was significant consistently across all the genetic backgrounds, test environments, and likely a wide range of pathogen races. QLr.cau-1AS explained 22.3-55.2% of leaf rust phenotypic variation, being comparable to Lr34 in effect size. A co-dominant SSR marker (gpw2246, http://wheat.pw.usda.gov/GG2/index.shtml ) was identified to be tightly linked to QLr.cau-1AS. Selection based on gpw2246 for QLr.cau-1AS was as effective as the selection based on cssfr5 for Lr34. QLr.cau-1AS will be helpful for increasing the genetic diversity of slow leaf-rusting resistance in wheat breeding programs.

Effect of intraoperative cell salvage on coagulation function outcomes in patients with massive post-Cesarean section hemorrhage.

OBJECTIVE: To examine the impact of using intraoperative cell salvage (ICS) for the restoration of coagulation function in cases of massive Post-Cesarean Section Hemorrhage (PCSH). METHODS: A retrospective analysis was conducted on 60 cases of massive PCSH meeting inclusion criteria at Suqian Maternity and Children's Hospital from January 2020 to July 2022. Patients were divided into two groups: allogeneic blood transfusion group (Group A, n = 30) and ICS group (Group B, n = 30), based on transfusion methods. Blood parameters, coagulation function, and adverse reactions were assessed before (T0) and after (T1) transfusion. Patients were categorized into good prognosis (GP) and poor prognosis (PP) groups based on adverse reaction occurrence. Clinical profiles were compared between groups, and multivariate binary logistic regression analysis was employed to evaluate the factors that may affect the prognosis in women with PCSH. RESULTS: No significant differences in routine blood parameters were observed between groups at T0 and T1 (P>0.05). At T0, no significant differences in PT, APTT, TT, or FIB were found between groups (P>0.05). Both groups showed a reduction in PT, APTT, and TT values at T1 compared to T0, with Group B experiencing a more significant decrease than Group A (P<0.05). FIB increased in both groups at T1 compared to T0, with Group B demonstrating a higher increase than Group A (P<0.05). Both groups showed increased blood pressure at T1 compared to T0, with Group B showing a more pronounced elevation than Group A (P<0.05). The occurrence of adverse reactions was significantly lower in Group B (1/30, 3.33%) compared to Group A (7/30, 23.33%) (P<0.05). Logistic regression analysis identified FIB<1.52 g/L and HR<45.35 times/min as factors associated with increased risk of unfavorable outcome in women with PCSH. CONCLUSION: In patients experiencing significant PCSH, ICS may lead to better postoperative recovery of blood parameters, faster restoration of coagulation function, and reduced risk of adverse events compared to ABT. Moreover, early detection of coagulation function and blood gas indexes is crucial for clinicians to implement timely prevention and treatment measures.

Parecoxib sodium attenuates acute lung injury following burns by regulating M1/M2 macrophage polarization through the TLR4/NF-κB pathway.

High temperature-induced burn injury often leads to an excessive inflammatory cascade resulting in multiple organ dysfunction syndrome, such as acute lung injury (ALI), in addition to skin tissue damage. As a specific COX2 inhibitor, parecoxib sodium suppresses the inflammatory response during burn injury. The effect of parecoxib sodium on ALI induced by burn injury and the associated molecular mechanism still need to be investigated. The role of parecoxib sodium in burn injury-induced ALI through the TLR4/NF-κB pathway was explored in the present study. A burn-induced ALI mouse model was constructed, and M1/M2 macrophages in lung tissue and markers involved in the TLR4/NF-κB signalling pathway were evaluated in bronchoalveolar lavage fluid (BALF) and MH-S mouse alveolar macrophages in vitro. The results indicated that parecoxib sodium attenuated lung injury after burn injury, decreased iNOS and TNF-α expression, increased IL-10 expression in BALF, and regulated the CD86-and CD206-mediated polarization of M1/M2 macrophages in lung tissue along with MH-S mouse alveolar macrophages. The effect of parecoxib sodium might be reversed by a TLR4 agonist. Overall, the results suggested that parecoxib sodium can regulate the polarization of M1/M2 macrophages through the TLR4/NF-κB pathway to attenuate ALI induced by skin burns.

Mapping and validation of a novel major QTL for resistance to stripe rust in four wheat populations derived from landrace Qishanmai.

Wheat yield has been constrained by stripe rust disease globally. A wheat landrace (Qishanmai, QSM) consistently showed lower stripe rust severities in multiple year studies than susceptible check varieties including Suwon11 (SW) at the adult plant stage. To detect QTL for reducing the severity in QSM, 1218 recombinant inbred lines (RILs) were developed from SW × QSM. QTL detection was conducted firstly using 112 RILs selected for similarity in pheno-morphological characters. The 112 RILs were assessed for stripe rust severity at the 2nd leaf, 6th leaf and flag leaf stages under field and greenhouse conditions, and genotyping was done primarily with a single nucleotide polymorphism (SNP) array. On the basis of these phenotypic and genotypic data, a major QTL (QYr.cau-1DL) was detected on chromosome 1D at the 6th leaf and flag leaf stages. Further mapping was conducted by genotyping 1218 RILs using new simple sequence repeat (SSR) markers, which were developed by referring to the sequences of the wheat line Chinese Spring (IWGSC RefSeq v1.0). QYr.cau-1DL was mapped within a 0.5 cM (5.2 Mb) interval delimited by the SSR markers 1D-320.58 and 1D-325.79. These markers were applied to select for QYr.cau-1DL by screening F2 or BC4F2 plants of the wheat crosses RL6058 × QSM, Lantian10 × QSM and Yannong21 × QSM. F2:3 or BC4F2:3 families derived from the selected plants were assessed for stripe rust resistance in the fields of two locations and in a greenhouse. Wheat plants carrying the resistant marker haplotype in homozygous state for QYr.cau-1DL showed lower stripe rust severities (by 44% to 48%) than plants lacking this QTL. The trial of RL6058 (a carrier of Yr18) × QSM also indicated that QYr.cau-1DL had larger effect than Yr18 on reducing severity; they acted synergistically, yielding an elevated level of stripe rust resistance.

Identification and Validation of a Major Quantitative Trait Locus for Adult Plant Resistance Against Leaf Rust From the Chinese Wheat Landrace Bai Qimai.

Leaf rust caused by Puccinia triticina Eriks. (Pt) is a common disease of wheat worldwide. The Chinese wheat landrace Bai Qimai (BQM) has shown high resistance to leaf rust for a prolonged period of time; the infected leaves of BQM displayed high infection types (ITs), but they showed low disease severities at the adult plant stage. To find quantitative trait loci (QTL) for resistance to leaf rust, 186 recombinant inbred lines from the cross Nugaines × BQM were phenotyped for leaf rust response in multiple field environments under natural Pt infections and genotyped using the 90K wheat single nucleotide polymorphism (SNP) chip and simple sequence repeat (SSR) markers. A total of 2,397 polymorphic markers were used for QTL mapping, and a novel major QTL (QLr.cau-6DL) was detected on chromosome 6DL from BQM. The effectiveness of QLr.cau-6DL was validated using the three additional wheat populations (RL6058 × BQM, Aikang58 × BQM, and Jimai22 × BQM). QLr.cau-6DL could significantly reduce leaf rust severities across all tested environments and different genetic backgrounds, and its resistance was more effective than that of Lr34. Moreover, QLr.cau-6DL acted synergistically with Lr34 to confer strong resistance to leaf rust. We believe that QLr.cau-6DL should have high potential value in the breeding of wheat cultivars with leaf rust resistance.

Compensatory roles of Protein Related to DAN and Cerberus (PRDC) decrease in pulmonary arterial hypertension.

Bone morphogenetic protein (BMP) signaling is commonly suppressed in patients with pulmonary arterial hypertension (PAH), but the compensatory mechanism of BMP signaling suppression is incompletely elucidated. This study aimed to investigate the role of PRDC, an antagonist of BMPs, in PAH and the underlying mechanism. Human lungs were collected and rat PAH was induced (monocrotaline, 60 mg/kg). BMP cascade and PRDC were detected in lungs and distal pulmonary artery smooth muscle cells (dPASMCs). In vitro cell experiments and in vivo supplementation of PRDC in hypertensive rats were subsequently performed. PRDC and BMP cascade all decreased in human and rat hypertensive lungs. Cell experiments confirmed that BMP2/4 inhibited dPASMCs proliferation by increasing cell cycle inhibitors (p21, p27), prevented dPASMCs migration by down-regulating MMP2/9 and up-regulating TIMP1/2 expression, and promoted dPASMCs apoptosis by up-regulating Bax, caspase3/9 and down-regulating Bcl-2 expression, as well as enhancing caspase3/7 activity, while, PRDC reversed the effects of BMP2/4 on dPASMCs proliferation, migration and apoptosis. In vivo trial found that PRDC supplementation deteriorated rat PAH in terms of pulmonary hemodynamics, vasculopathies and right ventricle hypertrophy. Taken together, compensatory decrease of PRDC in hypertensive lungs theoretically slow down the natural course of PAH, suggesting its therapeutic potential in PAH.

Comparative Effectiveness of Midazolam, Propofol, and Dexmedetomidine in Patients With or at Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

Background: Sedatives are commonly used in patients with or at risk for acute respiratory distress syndrome (ARDS) during mechanical ventilation. To systematically compare the outcomes of sedation with midazolam, propofol, and dexmedetomidine in patients with or at risk for ARDS. Methods: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of sedatives and the associated outcomes from the MIMIC-III database and the eICU Collaborative Research database. We performed a systematic study with six cohorts to estimate the relative risks of outcomes among patients administered different sedatives. Propensity score matching was performed to generate a balanced 1:1 matched cohort and to identify potential prognostic factors. The outcomes included hospital mortality, duration of mechanical ventilation, length of intensive care unit stay, length of hospitalization, and likelihood of being discharged home. Results: We performed 60 calibrated analyses among all groups and outcomes with 17,410 eligible patients. Sedation with dexmedetomidine was associated with a lower in-hospital mortality rate than sedation with midazolam and propofol or sedation without dexmedetomidine (p < 0.001). When compared with no sedation, the use of midazolam, propofol or dexmedetomidine was associated with a longer ICU stay and longer hospitalization duration (p < 0.01). Patients treated with midazolam were relatively less likely to be discharged home (p < 0.05). Conclusion: Patients treated with dexmedetomidine had a reduced risk of mortality. These data suggest that dexmedetomidine may be the preferred sedative in patients with or at risk for ARDS.

Comparative Efficacy of Fentanyl and Morphine in Patients with or At Risk for Acute Respiratory Distress Syndrome: A Propensity Score-Matched Cohort Study.

INTRODUCTION: Opioids are potent painkillers but can have severe adverse effects in the intensive care unit (ICU). The aim of this study was to compare the outcomes of fentanyl and morphine use among patients at risk for and with acute respiratory distress syndrome (ARDS). METHODS: We developed a dataset of real-world data to enable the comparison of the effectiveness and safety of opioids and the associated outcomes from the Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III database and the eICU Collaborative Research Database. Patients who were admitted to the ICU with a diagnosis of or at risk for ARDS and received mechanical ventilation for at least 12 h were included. Patients were enrolled sequentially into one of six groups in three cohorts: treated with fentanyl or not; treated with morphine or not; and treated with fentanyl or morphine. Propensity score matching and multivariable analyses were performed. RESULTS: Fentanyl was associated with higher in-hospital mortality in the propensity score-matched model but not in the linear regression model. The use of morphine was associated with a higher in-hospital mortality in both models. Both fentanyl and morphine were associated with longer duration of mechanical ventilation, ICU stay, and hospitalization and a decreased likelihood of being discharged home in both models. Notably, compared with morphine, fentanyl was associated with a lower mortality and an increased likelihood of being discharged home. CONCLUSIONS: Both fentanyl and morphine were independent risk factors for worse outcomes in patients with or at risk for ARDS. Compared with morphine, fentanyl may be preferred in these patients.

Associations Between Elevated Systolic Blood Pressure and Outcomes in Critically Ill Patients: A Retrospective Cohort Study and Propensity Analysis.

INTRODUCTION: Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. METHODS: This study was a retrospective analysis of data from the Medical Information Mart for Intensive Care (MIMIC) III database, which includes more than 1,000,000 SBP records from 12,820 patients. Associations of cumulative times at four SBP ranges (<100 mm Hg, 100-120 mm Hg, 120-140 mm Hg, and ≥140 mm Hg) with mortality (12-, 3-, 1-month mortality and in-hospital mortality) were evaluated. Restricted cubic splines and multivariable Cox regression models were employed to assess associations between mortality and cumulative times at SBP levels (4 levels: <2, 2-12, 12-36, and ≥36 h) over 72 h of ICU admission. Additionally, 120 mm Hg to 140 mm Hg was subdivided into <12 h (Group L) and ≥12 h (Group M) subsets and subjected to propensity-score matching and subgroup analyses. RESULTS: At 120 mm Hg to 140 mm Hg, level-4 SBP was associated with lower adjusted risks of mortality at 12 months (OR, 0.71; CI, 0.61-0.81), 3 months (OR, 0.72; CI, 0.61-0.85), and 1 month (OR, 0.61; CI, 0.48-0.79) and in the hospital (OR, 0.71; CI, 0.58-0.88) than level-1 SBP. The cumulative times at the other 3 SBP ranges (<100 mm Hg, 100-120 mm Hg, and ≥140 mm Hg) were not independent risk predictors of prognosis. Furthermore, Group M had lower 12-month mortality than Group L, which remained in the propensity-score matched and subgroup analyses. CONCLUSIONS: SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.

Higher versus lower mean arterial pressure target management in older patients having non-cardiothoracic surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: This study aimed to evaluate the effects of low versus high mean arterial pressure (MAP) levels on the incidence of postoperative delirium during non-cardiothoracic surgery in older patients. DESIGN: Multicenter, randomized, parallel-controlled, open-label, and assessor-blinded clinical trial. SETTING: University hospital. PATIENTS: Three hundred twenty-two patients aged ≥65 with an American Society of Anesthesiologists physical status of I-II who underwent non-cardiothoracic surgery with general anaesthesia. INTERVENTIONS: Participants were randomly assigned into a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) group during general anaesthesia. The study was conducted from November 2016 to February 2020. Participants were older patients having non-cardiothoracic surgery. The follow-up period ranged from 1 to 7 days after surgery. The primary outcome was the incidence of postoperative delirium. MAIN RESULTS: In total, 322 patients were included and randomized; 298 completed in-hospital delirium assessments [median (interquartile range) age, 73 (68-77) years; 173 (58.1%) women]. Fifty-four (18.1%) patients total, including 36 (24.5%) and 18 (11.9%) in the low-level and high-level MAP groups [relative risk (RR) 0.48, 95% confidence interval (CI) 0.25 to 0.87, P = 0.02], respectively, experienced postoperative delirium. The adjusted RR was 0.34 (95% CI 0.16 to 0.70, P < 0.01) in the multiple regression analysis. High-level MAP was associated with a shorter delirium span and a higher intraoperative urine volume than low-level MAP. CONCLUSIONS: In older patients during non-cardiothoracic surgery, high-level blood pressure management might help reduce the incidence of postoperative delirium.