Hemostasis Using Prothrombin Complex Concentrate in Patients Undergoing Cardiac Surgery: Systematic Review with Meta-Analysis.

OBJECTIVE: The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents undergoing cardiac surgery. METHODS: PubMed®, Embase, and Cochrane Líbrary databases were searched for studíes ínvestigating PCC administratíon duríng cardiac surgery published before September 10, 2022. Mean dífference (MD) wíth 95% confidence interval (CI) was applíed to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. RESULTS: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not assocíated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolíc events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase ín atríal fibríllatíon events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. CONCLUSION: The use of PCC in cardiac surgery did not correlate with mortality, length of hospítal stay, thoracic drainage, atríal fibríllatíon, myocardíal ínfarction, and thromboembolíc events. However, PCC sígnificantly improved postoperatíve intensíve care unít length of stay, bleedíng, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes ín patients undergoing cardíac surgery.

Hemostasis Using Prothrombin Complex Concentrate in Patients Undergoing Cardiac Surgery: Systematic Review with Meta-Analysis

ABSTRACT Objective: The purpose of present study was to comprehensively explore the efficacy and safety of prothrombin complex concentrate (PCC) to treat massive bleeding in patients undergoing cardiac surgery. Methods: PubMed®, Embase, and Cochrane Library databases were searched for studies investigating PCC administration during cardiac surgery published before September 10, 2022. Mean difference (MD) with 95% confidence interval (CI) was applied to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. Results: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not associated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolic events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase in atrial fibrillation events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. Conclusion: The use of PCC in cardiac surgery did not correlate with mortality, length of hospital stay, thoracic drainage, atrial fibrillation, myocardial infarction, and thromboembolic events. However, PCC significantly improved postoperative intensive care unit length of stay, bleeding, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes in patients undergoing cardiac surgery.

Thoracic perivascular adipose tissue inhibits VSMC apoptosis and aortic aneurysm formation in mice via the secretome of browning adipocytes.

Abdominal aortic aneurysm (AAA) is a dangerous vascular disease without any effective drug therapies so far. Emerging evidence suggests the phenotypic differences in perivascular adipose tissue (PVAT) between regions of the aorta are implicated in the development of atherosclerosis evidenced by the abdominal aorta more vulnerable to atherosclerosis than the thoracic aorta in large animals and humans. The prevalence of thoracic aortic aneurysms (TAA) is much less than that of abdominal aortic aneurysms (AAA). In this study we investigated the effect of thoracic PVAT (T-PVAT) transplantation on aortic aneurysm formation and the impact of T-PVAT on vascular smooth muscle cells. Calcium phosphate-induced mouse AAA model was established. T-PVAT (20 mg) was implanted around the abdominal aorta of recipient mice after removal of endogenous abdominal PVAT (A-PVAT) and calcium phosphate treatment. Mice were sacrificed two weeks after the surgery and the maximum external diameter of infrarenal aorta was measured. We found that T-PVAT displayed a more BAT-like phenotype than A-PVAT; transplantation of T-PVAT significantly attenuated calcium phosphate-induced abdominal aortic dilation and elastic degradation as compared to sham control or A-PVAT transplantation. In addition, T-PVAT transplantation largely preserved smooth muscle cell content in the abdominal aortic wall. Co-culture of T-PVAT with vascular smooth muscle cells (VSMCs) significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. RNA sequencing analysis showed that T-PVAT was enriched by browning adipocytes and anti-apoptotic secretory proteins. We further verified that the secretome of mature adipocytes isolated from T-PVAT significantly inhibited H2O2- or TNFα plus cycloheximide-induced VSMC apoptosis. Using proteomic and bioinformatic analyses we identified cartilage oligomeric matrix protein (COMP) as a secreted protein significantly increased in T-PVAT. Recombinant COMP protein significantly inhibited VSMC apoptosis. We conclude that T-PVAT exerts anti-apoptosis effect on VSMCs and attenuates AAA formation, which is possibly attributed to the secretome of browning adipocytes.

Influence of Collective Esophageal Speech Training on Self-efficacy in Chinese Laryngectomees: A Pretest-posttest Group Study.

Total laryngectomy affects the speaking functions of many patients. Speech deprivation has great impacts on the quality of life of patients, especially on self-efficacy. Learning esophageal speech represents a way to help laryngectomees speak again. The purpose of this study was to determine the influence of collective esophageal speech training on self-efficacy of laryngectomees. In this study, 28 patients and 30 family members were included. The participants received information about training via telephone or a WeChat group. Collective esophageal speech training was used to educate laryngectomees on esophageal speech. Before and after collective esophageal speech training, all participants completed the General Self-Efficacy Scale (GSES) to assess their perceptions on self-efficacy. Through the training, laryngectomees recovered their speech. After the training, the self-efficacy scores of laryngectomees were higher than those before the training, with significant differences noted (T<0.05). However, family members' scores did not change significantly. In conclusion, collective esophageal speech training is not only convenient and economical, but also improves self-efficacy and confidence of laryngectomees. Greater self-efficacy is helpful for laryngectomees to master esophageal speech and improve their quality of life. In addition, more attention should be focused on improving the self-efficacy of family members and making them give full play to their talent and potential on laryngectomees' voice rehabilitation.

Combination of BMSCs-laden acellular nerve xenografts transplantation and G-CSF administration promotes sciatic nerve regeneration.

Peripheral nerve gaps often lead to interrupted innervation, manifesting as severe sensory and motor dysfunctions. The repairs of the nerve injuries have not achieved satisfactory curative effects in clinic. The transplantation of bone marrow stromal cells (BMSCs)-laden acellular nerve xenografts (ANX) has been proven more effective than the acellular nerve allografting. Besides, granulocyte colony-stimulating factor (G-CSF) can inhibit inflammation and apoptosis, and thus is conducive to the microenvironmental improvement of axonal regeneration. This study aims to investigate the joint effect of BMSCs-seeded ANX grafting and G-CSF administration, and explore the relevant mechanisms. Adult SD rats were divided into five groups randomly: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group, and autograft group. Eight weeks after transplantation, the detection of praxiology and neuroelectrophysiology was conducted, and then the morphology of the regenerated nerves was analyzed. The inflammatory response and apoptosis in the nerve grafts as well as the expression of the growth-promoting factors in the regenerated tissues were further assayed. G-CSF intervention and BMSCs implanting synergistically promoted peripheral nerve regeneration and functional recovery following ANX bridging, and the restoration effect was matchable with that of the autologous nerve grafting. Moreover, local inflammation was alleviated, the apoptosis of the seeded BMSCs was decreased, and the levels of the neuromodulatory factors were elevated. In conclusion, the union application of BMSCs-implanted ANX and G-CSF ameliorated the niche of neurotization and advanced nerve regeneration substantially. The strategy achieved the favorable effectiveness as an alternative to the autotransplantation.

Synergistic effects of G-CSF and bone marrow stromal cells on nerve regeneration with acellular nerve xenografts.

Peripheral nerve defects result in severe denervation presenting sensory and motor functional incapacitation. Currently, a satisfactory therapeutic treatment promoting the repair of injured nerves is not available. As shown in our previous study, acellular nerve xenografts (ANX) implanted with bone marrow stromal cells (BMSCs) replaced allografts and promoted nerve regeneration. Additionally, granulocyte-colony stimulating factor (G-CSF) has been proven to mobilize supplemental cells and enhance vascularization in the niche. Thus, the study aimed to explore whether the combination of G-CSF and BMSC-laden ANX exhibited a synergistic effect. Adult Sprague-Dawley (SD) rats were randomly divided into five groups: ANX group, ANX combined with G-CSF group, BMSCs-laden ANX group, BMSCs-laden ANX combined with G-CSF group and autograft group. Electrophysiological parameters and weight ratios of tibialis anterior muscles were detected at 8 weeks post-transplantation. The morphology of the regenerated nerves was assayed, and growth-promoting factors present in the nerve grafts following G-CSF administration or BMSCs seeding were also investigated. Nerve regeneration and functional rehabilitation induced by the combination therapy were significantly advanced, and the rehabilitation efficacy was comparable with autografting. Moreover, the expression of Schwann cell markers, neurotrophic factors and neovessel markers in the nerve grafts was substantially increased. In conclusion, G-CSF administration and BMSCs transplantation synergistically promoted the regeneration of ANX-bridged nerves, which offers a superior strategy to replace autografts in repairing peripheral nerve injuries.

ARHGAP1 overexpression inhibits proliferation, migration and invasion of C-33A and SiHa cell lines.

ARHGAP1, also known as RhoGAP, RhoGAP1, CDC42GAP and p50rhoGAP, is officially named Ras homology (Rho) GTPase-activating protein 1, which is one of the key members of RhoGAPs. Growing evidences demonstrate that several RhoGAPs are suppressed or downregulated in cancers. Thus, the aim of this study was to explore the effects of ARHGAP1 on cervical carcinoma cells. The human cervical carcinoma cells C-33A and SiHa were transduced with lentivirus targeting ARHGAP1 (lenti-ARHGAP1). Cellular proliferation, migration and invasion assays, as well as quantitative real-time polymerase chain reaction and Western blot assays, were performed in the control, negative control (infected with lentivirus) and ARHGAP1+-infected groups. Results showed that overexpression of ARHGAP1 markedly inhibited the proliferation of both C-33A and SiHa cells at 24 h, 48 h and 72 h in a time-dependent manner (n=3, P<0.01). Migration and invasion of C-33A and SiHa cells were suppressed after the transduction with lenti-ARHGAP1 compared with the controls (n=3, P<0.01). In addition, several tumor cellular process-related proteins, such as matrix metallopeptidase 2, zinc finger E-box binding homeobox 1, Cyclin B1, twist family bHLH transcription factor 1 and proliferating cell nuclear antigen, were all downregulated in ARHGAP1-overexpressed C-33A and SiHa cells and proved to be targets of ARHGAP1. This study indicated that ARHGAP1 may have a positive function on antitumor activity in the treatment of cervical cancer.

Gelsolin Promotes Radioresistance in Non-Small Cell Lung Cancer Cells Through Activation of Phosphoinositide 3-Kinase/Akt Signaling.

Gelsolin is an actin-binding protein and acts as an important regulator of cell survival. This study aimed to determine the function of gelsolin in the radioresistance of non-small cell lung cancer cells. We examined the expression of gelsolin in radioresistant A549 and H460 cells and their parental cells. The effects of gelsolin overexpression and knockdown on the clonogenic survival and apoptosis of non-small cell lung cancer cells after irradiation were studied. The involvement of phosphoinositide 3-kinase/Akt signaling in the action of gelsolin was checked. We found that gelsolin was significantly upregulated in radioresistant A549 and H460 cells. Overexpression of gelsolin significantly ( P < .05) increased the number of colonies from irradiated A549 and H460 cells compared to transfection of empty vector. In contrast, knockdown of gelsolin significantly ( P < .05) suppressed colony formation after irradiation. Gelsolin-overexpressing cells displayed reduced apoptosis in response to irradiation, which was coupled with decreased levels of cleaved caspase-3 and poly adenosine diphosphate-ribose polymerase. Ectopic expression of gelsolin significantly ( P < .05) enhanced the phosphorylation of Akt compared to nontransfected cells. Pretreatment with the phosphoinositide 3-kinase inhibitor LY294002 (20 µmol/L) significantly decreased clonogenic survival and enhanced apoptosis in gelsolin-overexpressing A549 and H460 cells after irradiation. Taken together, gelsolin upregulation promotes radioresistance in non-small cell lung cancer cells, at least partially, through activation of phosphoinositide 3-kinase/Akt signaling.

Neurochemical features of endomorphin-2-containing neurons in the submucosal plexus of the rat colon.

AIM: To investigate the distribution and neurochemical phenotype of endomorphin-2 (EM-2)-containing neurons in the submucosal plexus of the rat colon. METHODS: The mid-colons between the right and left flexures were removed from rats, and transferred into Kreb's solution. For whole-mount preparations, the mucosal, outer longitudinal muscle and inner circular muscle layers of the tissues were separated from the submucosal layer attached to the submucosal plexus. The whole-mount preparations from each rat mid-colon were mounted onto seven gelatin-coated glass slides, and processed for immunofluorescence histochemical double-staining of EM-2 with calcitonin gene-related peptide (CGRP), choline acetyltransferase (ChAT), nitric oxide synthetase (NOS), neuron-specific enolase (NSE), substance P (SP) and vasoactive intestinal peptide (VIP). After staining, all the fluorescence-labeled sections were observed with a confocal laser scanning microscope. To estimate the extent of the co-localization of EM-2 with CGRP, ChAT, NOS, NSE, SP and VIP, ganglia, which have a clear boundary and neuronal cell outline, were randomly selected from each specimen for this analysis. RESULTS: In the submucosal plexus of the mid-colon, many EM-2-immunoreactive (IR) and NSE-IR neuronal cell bodies were found in the submucosal plexus of the rat mid-colon. Approximately 6 ± 4.2 EM-2-IR neurons aggregated within each ganglion and a few EM-2-IR neurons were also found outside the ganglia. The EM-2-IR neurons were also immunopositive for ChAT, SP, VIP or NOS. EM-2-IR nerve fibers coursed near ChAT-IR neurons, and some of these fibers were even distributed around ChAT-IR neuronal cell bodies. Some EM-2-IR neuronal cell bodies were surrounded by SP-IR nerve fibers, but many long processes connecting adjacent ganglia were negative for EM-2 immunostaining. Long VIP-IR processes with many branches coursed through the ganglia and surrounded the EM-2-IR neurons. The percentages of the EM-2-IR neurons that were also positive for ChAT, SP, VIP or NOS were approximately 91% ± 2.6%, 36% ± 2.4%, 44% ± 2.5% and 44% ± 4.7%, respectively, but EM-2 did not co-localize with CGRP. CONCLUSION: EM-2-IR neurons are present in the submucosal plexus of the rat colon and express distinct neurochemical markers.

Identification of three novel linear B-cell epitopes on the VP5 protein of BTV16.

Bluetongue virus (BTV) VP5 protein is an important antigenic protein which is centrally involved in serotype determination and the virus entry process. Very little is known about the B-cell epitopes on the BTV VP5 protein recognized by humoral immune responses. In this study, we generated five BTV16 VP5 protein-specific monoclonal antibodies (MAbs), named 3B11, 2B10, 1H7, 4A6 and 3G9, and defined the linear epitopes recognized by MAbs using a series of peptides expressed as maltose-binding protein (MBP)-fusion polypeptides. Three novel linear B-cell epitopes were identified: 3B11 and 3G9 recognized the motif ITANTREIQHIKEE; 2B10 recognized the motif LSGID; and 4A6 recognized the motif STMVKEYRQKIDALKA. Exact sequences corresponding to the three motifs identified were found in the BTV16 VP5 protein ((310)ITANTREIQHIKEE(323), (265)LSGID(269) and (188)STMVKEYRQKIDALKA(203)). These motifs represent the minimal linear peptide sequence required for MAb reactivity, as binding of each MAb was abolished when additional amino acids were removed from the amino and carboxy termini of the peptide. Amino acid sequence alignment indicated that three epitopes were totally conserved among different BTV16 strains. The MAbs generated along with identified epitopes will be useful for examining VP5 protein function and the development of epitope-based marker vaccines against BTV.

Clinical features and risk factors of pure red cell aplasia following major ABO-incompatible allogeneic hematopoietic stem cell transplantation.

The objective of this paper was to study the incidence, risk factors, clinical outcome, management and prevention of pure red cell aplasia (PRCA) following major ABO-incompatible allogeneic hematopoietic stem cell transplantation (allo-HSCT). We retrospectively analyzed 11 cases of PRCA from a series of 42 patients undergoing major ABO-incompatible allo-HSCT from April 1997 to December 2005. Eleven out of the 42 patients developed PRCA (26.1%). All the 11 cases of PRCA were in blood group O recipients of grafts from blood group A donor (n = 9) or blood group B donor (n = 2). The following factors were associated with an increased risk of PRCA: (1) blood group O recipient; (2) blood group A donor; and (3) blood group O/A in recipient/donor pair. Only blood group O/A in recipient/donor pair was identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Six patients who received donor-type plasma exchange did not develop PRCA and among them 5 cases were the blood group O recipients. Eight patients obtained spontaneous remission and in the remaining 3 patients 2 with long-lasting PRCA were successfully treated with plasma exchange with donor-type plasma replacement and the other one who was also complicated by EBV-associated lymphoproliferative disorder (EBV-PTLD) responded rapidly to anti-CD20 monoclonal antibody and achieved complete resolution of clinical finding and symptom of both EBV-PTLD and PRCA. We conclude that blood group A/O in donor/recipient pair is identified as being significantly associated with the occurrence of PRCA by multivariate analysis. Donor-type plasma exchange and anti-CD20 monoclonal antibody is an effective approach for the treatment of PRCA. PRCA could be prevented by plasma exchange prior to transplantation.

The catecholamine-beta-adrenoreceptor-cAMP system and prediction of cardiovascular events in hypertension.

Although the importance of elevated circulating plasma catecholamines on cardiac structural and functional remodelling of hypertension is well documented, it is unclear whether the catecholamine-beta-adrenoreceptor (beta AR)-cAMP system can predict different cardiovascular events. 2. A total of 601 identified hypertensive patients with baseline and follow-up plasma levels of noradrenaline (NA) and adrenaline (Adr), lymphocyte beta AR density (B(max)) and intra-lymphocyte cAMP levels in peripheral blood (last examination 60+/-26 months apart) were followed up for an additional 24+/-12 months. 3. After the last follow up, a composite end-point of cardiovascular death, non-fatal myocardial infarction (MI) and stroke occurred in 139 patients (23.1%). In Cox analyses, adjusting for other standard factors as well as treatment effect, NA (hazard ratio 1.22; 95% confidence interval (CI) 1.17-1.28; P=0.0008), Adr (hazard ratio 1.53; 95% CI 1.18-2.00; P=0.002), beta AR (hazard ratio 1.12; 95% CI 1.06-1.17; P=0.007) and cAMP (hazard ratio 1.15; 95% CI 1.09-1.21; P=0.005) separately predicted cardiovascular mortality. Noradrenaline, Adr, beta AR and intra-lymphocyte cAMP separately predicted fatal/non-fatal MI; NA and Adr predicted fatal/non-fatal stroke, whereas B(max) and intra-lymphocyte cAMP levels were not a significant predictor of fatal/non-fatal stroke. When stratifying the study population by NA or Adr (median 4 nmol/L), B(max) (median 600 fmol/10(7) cells) and cAMP (median 5.0 pmol/mg protein) above and below the median values in both parameters categories, patients above the median had composite cardiovascular end-point (all P<0.001) and high cardiovascular death (all P<0.01, log-rank test). 4. These results suggest that plasma NA and Adr are significant predictors of cardiovascular mortality, MI and stroke. The B(max) and intra-lymphocyte cAMP levels are significant predictors of cardiovascular mortality and MI, but not stroke.

Cardiac risk stratification in patients with congestive heart failure: a catecholamines-beta-adrenoceptor-cAMP pathway.

OBJECTIVE: To investigate the stratification risk of catecholamines-beta-adrenoceptor (beta-AR)-cAMP pathway for cardiogenic death events in patients with congestive heart failure (CHF). METHODS: A total of 83 identified CHF patients with a baseline and follow-up plasma levels of norepinephrine (NE) and epinephrine (E), lymphocytes beta-AR density (Bmax), and intralymphocyte cAMP content in peripheral blood were followed up. Major cardiogenic death events were registered. RESULTS: The period between the initial entry and the last follow-up measurement were 51 +/- 16 months, the total duration of clinical follow-up after the last measurement were 14 +/- 8 months. During follow-up, 39 patients died of cardiogenic (sudden death 17 patients, worsening heart failure 22 patients). Persistence of high NE, E, and cAMP from baseline to follow-up were confirmed as risk predicting factors of cardiovascular events. Persistence NE above 4.0 nmol/L, E above 3.5 nmol/L, and the intralymphocyte cAMP content above 3.5 pmd x mg(-1) x pro(-1) from baseline to follow-up were significant adverse prognostic predictors. The major cardiogenic death events rates per 100 patients-years were 1.33 and 4.82 in patients with NE below and above 4.0 nmol/L (HR: 2.91; 95% CI: 1.08-7.33; P = 0.015); were 1.42 and 4.36 in the patients with E levels below and above 3.5 nmol/L (HR: 2.64; 95% CI: 1.02-6.41; P = 0.019); were 1.81 and 4.67 in the patients with the intralymphocyte cAMP content below and above 3.5 pmd x mg(-1) x pro(-1) (HR: 2.79; 95% CI: 1.04-6.83; P = 0.017), but difference was not significant between the beta-AR density below and above median. CONCLUSIONS: Persistent increase in circulating catecholamines and intralymphocyte cAMP content may increase the long-term mortality in CHF patients.