Background: This study presents an overview of our technique and the perioperative outcomes for the first 100 patients who underwent minimally invasive endoscopic-assisted off-pump multivessel bypass grafting (endoscopic coronary artery bypass [endo-CAB]) at the Catharina Hospital in Eindhoven. Methods: The first 100 patients undergoing multivessel endo-CAB from May 2022 to March 2024 were included in this retrospective, single-center, observational study (N=100).The study encompassed both elective and urgent surgical revascularization. In all cases, endoscopic-assisted harvesting of the internal mammary artery, radial artery, or saphenous vein was performed, followed by beating-heart anastomoses through a mini-thoracotomy. Results: A total of 226 distal anastomoses were performed, utilizing 102 left internal mammary arteries, 80 radial arteries, 30 right internal mammary arteries, and 14 saphenous veins. On average, each patient had 2.3 anastomoses. A Y graft configuration was employed in 78 patients, in-situ bilateral internal mammary artery inflow in 19 patients, and a proximal aortic graft in 3 patients. Four patients underwent concurrent arrhythmia surgery.Eleven patients received hybrid revascularization. There was 1 conversion to sternotomy (1%) and 3 instances where cardiopulmonary bypass was required (3%). The median operation time was 3.3 hours (interquartile range, 3.0–3.7 hours), and the median hospital stay was 4.0 days (interquartile range, 3–4 days). The in-hospital mortality rate was 1%. Conclusion Multivessel off-pump endo-CAB surgery can be safely performed with endoscopic-assisted conduit harvesting. Combining the benefits of a minimally invasive and anaortic approach may improve perioperative outcomes for patients requiring surgical revascularization. Further studies are necessary to establish the role of this technique in routine coronary surgery.

Background: This study presents an overview of our technique and the perioperative outcomes for the first 100 patients who underwent minimally invasive endoscopic-assisted off-pump multivessel bypass grafting (endoscopic coronary artery bypass [endo-CAB]) at the Catharina Hospital in Eindhoven. Methods: The first 100 patients undergoing multivessel endo-CAB from May 2022 to March 2024 were included in this retrospective, single-center, observational study (N=100).The study encompassed both elective and urgent surgical revascularization. In all cases, endoscopic-assisted harvesting of the internal mammary artery, radial artery, or saphenous vein was performed, followed by beating-heart anastomoses through a mini-thoracotomy. Results: A total of 226 distal anastomoses were performed, utilizing 102 left internal mammary arteries, 80 radial arteries, 30 right internal mammary arteries, and 14 saphenous veins. On average, each patient had 2.3 anastomoses. A Y graft configuration was employed in 78 patients, in-situ bilateral internal mammary artery inflow in 19 patients, and a proximal aortic graft in 3 patients. Four patients underwent concurrent arrhythmia surgery.Eleven patients received hybrid revascularization. There was 1 conversion to sternotomy (1%) and 3 instances where cardiopulmonary bypass was required (3%). The median operation time was 3.3 hours (interquartile range, 3.0–3.7 hours), and the median hospital stay was 4.0 days (interquartile range, 3–4 days). The in-hospital mortality rate was 1%. Conclusion Multivessel off-pump endo-CAB surgery can be safely performed with endoscopic-assisted conduit harvesting. Combining the benefits of a minimally invasive and anaortic approach may improve perioperative outcomes for patients requiring surgical revascularization. Further studies are necessary to establish the role of this technique in routine coronary surgery.

Background: This study presents an overview of our technique and the perioperative outcomes for the first 100 patients who underwent minimally invasive endoscopic-assisted off-pump multivessel bypass grafting (endoscopic coronary artery bypass [endo-CAB]) at the Catharina Hospital in Eindhoven. Methods: The first 100 patients undergoing multivessel endo-CAB from May 2022 to March 2024 were included in this retrospective, single-center, observational study (N=100).The study encompassed both elective and urgent surgical revascularization. In all cases, endoscopic-assisted harvesting of the internal mammary artery, radial artery, or saphenous vein was performed, followed by beating-heart anastomoses through a mini-thoracotomy. Results: A total of 226 distal anastomoses were performed, utilizing 102 left internal mammary arteries, 80 radial arteries, 30 right internal mammary arteries, and 14 saphenous veins. On average, each patient had 2.3 anastomoses. A Y graft configuration was employed in 78 patients, in-situ bilateral internal mammary artery inflow in 19 patients, and a proximal aortic graft in 3 patients. Four patients underwent concurrent arrhythmia surgery.Eleven patients received hybrid revascularization. There was 1 conversion to sternotomy (1%) and 3 instances where cardiopulmonary bypass was required (3%). The median operation time was 3.3 hours (interquartile range, 3.0–3.7 hours), and the median hospital stay was 4.0 days (interquartile range, 3–4 days). The in-hospital mortality rate was 1%. Conclusion Multivessel off-pump endo-CAB surgery can be safely performed with endoscopic-assisted conduit harvesting. Combining the benefits of a minimally invasive and anaortic approach may improve perioperative outcomes for patients requiring surgical revascularization. Further studies are necessary to establish the role of this technique in routine coronary surgery.

Bats are flying mammals with unique immune systems that allow them to hold many pathogens. Hence, they are recognised as the reservoir of many zoonotic pathogens. In this study, we performed molecular detection to detect coronaviruses, paramyxoviruses, pteropine orthoreoviruses and dengue viruses from samples collected from insectivorous bats in Krau Reserve Forest. One faecal sample from Rhinolophus spp. was detected positive for coronavirus. Based on BLASTN, phylogenetic analysis and pairwise alignment-based sequence identity calculation, the detected bat coronavirus is most likely to be a bat betacoronavirus lineage slightly different from coronavirus from China, Philippines, Thailand and Luxembourg. In summary, continuous surveillance of bat virome should be encouraged, as Krau Reserve Forest reported a wide spectrum of biodiversity of insectivorous and fruit bats. Moreover, the usage of primers for the broad detection of viruses should be reconsidered because geographical variations might possibly affect the sensitivity of primers in a molecular approach.

Background: Feline mammary carcinoma (FMC) is one of the most prevalent malignancies of female cats. FMC is highly metastatic and thus leads to poor disease outcomes. Among all metastases, liver metastasis occurs in about 25% of FMC patients. However, the mechanism underlying hepatic metastasis of FMC remains largely uncharacterized. Results: Herein, we demonstrate that FMC-derived extracellular vesicles (FMC-EVs) promotes the liver metastasis of FMC by activating hepatic stellate cells (HSCs) to prime a hepatic premetastatic niche (PMN). Moreover, we provide evidence that sphingosine kinase 1 (SK1) delivered by FMC-EV was pivotal for the activation of HSC and the formation of hepatic PMN. Depletion of SK1 impaired cargo sorting in FMC-EV and the EV-potentiated HSC activation, and abol‑ ished hepatic colonization of FMC cells. Conclusions Taken together, our findings uncover a previously uncharacterized mechanism underlying liver-metas‑ tasis of FMC and provide new insights into prognosis and treatment of this feline malignancy.

OBJECTIVE：To evaluate the econo mics of pembrolizumab in the second-line treatment of advanced hepatocellular carcinoma in China. METHODS ：From the perspective of Chinese healthcare system ，a three-state PartSA model and Markov model were established ；the cost and utility for the second-line treatment of advanced hepatocellular carcinoma in China were compared between pembrolizumab and placebo. The circulation cycle of the model was 3 weeks and the study time limit was lifetime；one-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS ：PartSA results showed that the ICER for the second-line treatment of advanced hepato- cellular carcinoma with pembrolizumab was 1 266 846.18 yuan/QALY，which is far more than 1-3 times of China ’s per capita GDP in 2020. The results of one-way sensitivity analysis showed that the three parameters that had the greatest impact on ICER were the PFS status utility of the placebo group ，the PFS status utility of the pembrolizumab group ，and the cost of pembrolizumab. The results of probability sensitivity analysis verified the robustness of the base-case analysis. The scenario analysis showed that the treatment cost of pembrolizumab had dropped significantly when the charity donation of pembrolizumab was considered. Although it was still not economical ，ICER was close to 3 times of per capita GDP of China in 2020. When WTP threshold was 1 and 3 times of China ’s per capita GDP ，the economic prices of pabolizumab （100 mg）were 4 157.67 and 5 829.24 yuan，respectively. The results of Markov model were similar to those of PartSA model. CONCLUSIONS ：Under the WTP threshold of 1-3 times China ’s per capita GDP in 2020，pembrolizumab is not economical for second-line treatment of advanced hepatocellular carcinoma.

Aims: To determine abundance of potential pathogenic microorganisms in pangasius and tilapia farms in five major fish-producing areas in Bangladesh by PCR approaches. Methodology and results: Important microbial water quality indicators were studied in water of 38 fish farms producing pangasius (Pangasianodon hypophthalmus) and tilapia (Oreochromis niloticus) in five major fish-producing areas of Bangladesh. The parameters included physicochemical data and PCR detection of total coliforms and E. coli, species of potentially pathogenic Vibrio, and cyanobacterial genes encoding the toxins microcystin and saxitoxin. Quantitative PCR showed that coliform bacteria occurred in all fish farms with densities from one to 2.2 × 105 per mL, while E. coli ranged from none to 5.0 × 104 per mL. Numbers of total coliforms and E. coli were higher in pangasius farms than in tilapia farms, and when high abundances occurred, coliform bacteria and E. coli bacteria co-varied. Detection of Vibrio-specific genes indicated presence of Vibrio species in 76% of the farms and included V. vulnificus and V. cholerae. The human pathogen type of V. cholerae (carrying the ctxA gene) and the fish pathogen V. parahaemolyticus were not detected. The microcystin-encoding mcyE gene ranged from undetectable to 2.6 × 105 copies per mL and tended to be highest in pangasius farms. The saxitoxin-encoding gene sxtA was not found in any of the farms. Conclusion, significance and impact of study Based on the high abundance of especially coliform bacteria and E. coli, we recommend more efficient water quality monitoring systems to improve detection and control of fecal coliforms and to reduce presence of microcystin-producing cyanobacteria in aquaculture farms in Bangladesh
Water Quality ; Tilapia ; Catfishes

OBJECTIVE：To investigate the effects of Periplaneta americana extract on the proliferation and apoptosis of human non-small cell lung cancer A 549 cells as well as its possible mechanism. METHODS ：The dry bodies of P. americana were soaked with 90％ ethanol and eluted with gradient water-methanol by polyamide column chromatography. The 20％，30％，40％， 50％，60％，70％，80％，90％ methanol elution sites （YS-A-H）were obtained. MTT method was used to screen the active site ， and the inhibition rate of different doses of active site was detected. Flow cytometry was adopted to detect cell apoptosis ，cell cycle and mitochondrial membrane potential of cells after treated with different doses of active site. RESULTS ：Half inhibition concentrations of YS-A-H were （95.25±8.42），（129.93±7.24），（221.28±12.68），（275.39±14.87），（276.76±16.32），（31.90± 5.34），（163.15±6.97），（122.81±8.36）μg/mL，respectively. YS-F had the strongest activity. After treated with 3，9，27，81 μg/mL YS-F for 24，48，72 h，cell proliferation inhibitory rate was increased significantly at different time points ；after treated for 48，72 h，that was significantly higher than same group after treated for 24 h；after 72 h treatment ，that was significantly higher than same group after 48 h treatment （P＜0.01）. There was no significant effect of 24 h treatment of 3 μg/mL YS-F and 72 h treatment of 9 μg/mL YS-F on the percentage of cells in the late stage of necrosis，24 h treatment of 3 μg/mL YS-F on the percentage of cells in G2/M phase and 48 h treatment of 3 μg/mL YS-F on the reduction rate of mitochondrial membrane potential（P＞0.05）. The percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis，as well as the percentage of cells in the Sub-G 0/G1 and S phase at each time point were significantly increased in other different doses groups ，while the percentage of cells in G 0/G1 and G 2/M phase was decreased significantly （P＜0.01）. In each dose group，the percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis （except for the percentage of cells in the late stage of necrosis treated with YS-F 9 μg/mL for 72 h）and the percentage of cells in Sub-G 0/G1 phase，G2/M phase （except for YS-F 27，81 μg/mL for 48 h）after treated for 48，72 h were significantly higher than same group after 24 h of treatment ；the percentage of cells in G 0/G1 phase，S phase and G 2/M phase （except for YS-F 9 μg/mL for 48 h）after treated for 48，72 h were significantly lower than same group after 24 h of treatment （P＜0.01）；the percentage of cells in the early stage of apoptosis ，the late stage of apoptosis and the early stage of necrosis ，the late stage of necrosis （except for the percentage of cells in the late stage of apoptosis and early stage of necrosis when treated with YS-F 27 μg/mL for 72 h，the percentage of cells in the late stage of necrosis when treated with YS-F 3，9 μg/mL for 72 h were decreased significantly ）and the percentage of cells in S phase （except for YS-F 3 μg/mL for 72 h）and Sub-G 0/G1 phase after treated for 72 h were significantly higher than same group after 48 h of treatment ，while the percentage of cells in G 0/G1 and G 2/M phase were significantly lower than same group after 48 h of treatment （P＜0.01）. After treated with YS-F 9，27，81 μg/mL for 48 h，the reduction rate of cell mitochondrial membrane potential was increased significantly ；YS-F 27，81 μg/mL groups were significantly higher than YS-F 9 μg/mL group，and YS-F 81 μg/mL group was significantly higher than YS-F 27 μg/mL group. CONCLUSIONS：YS-F can inhibit the proliferation and promote the apoptosis of A 549 cells by preventing cell transformation from S phase to G 2/M phase ，and reducing mitochondrial membrane potential ，in time-dependent or dose-dependent manner.

The syndrome of the trephined is a neurologic phenomenon that manifests as sudden decline in cognition, behavior, and sensorimotor function due to loss of intracranial domain. This scenario typically occurs in the setting of large craniectomy defects, resulting from trauma, infection, and/or oncologic extirpation. Cranioplasty has been shown to reverse these symptoms by normalizing cerebral hemodynamics and metabolism. However, successful reconstruction may be difficult in patients with complex and/or hostile calvarial defects. We present the case of a 48-year-old male with a large cranial bone defect, who failed autologous cranioplasty secondary to infection, and developed rapid neurologic deterioration leading to a near-vegetative state. Following debridement and antibiotic therapy, delayed cranioplasty was accomplished using a polyetheretherketone (PEEK) implant with free chimeric latissimus dorsi/serratus anterior myocutaneous flap transfer for vascularized resurfacing. Significant improvements in cognition and motor skill were noted in the early postoperative period. At 6-month follow-up, the patient had regained the ability to speak, ambulate and self-feed—correlating with evidence of cerebral/ventricular re-expansion on computed tomography. Based on our findings, we advocate delayed alloplastic implantation with total vascularized soft tissue coverage as a viable alternative for reconstructing extensive, hostile calvarial defects in patients with the syndrome of the trephined.
Cognition ; Craniocerebral Trauma ; Debridement ; Follow-Up Studies ; Free Tissue Flaps ; Hemodynamics ; Humans ; Male ; Metabolism ; Middle Aged ; Motor Skills ; Myocutaneous Flap ; Neurologic Manifestations ; Postoperative Period ; Reconstructive Surgical Procedures

Exotoxins produced by Actinobacillus (A.) pleuropneumoniae (Apx) play major roles in the pathogenesis of pleuropneumonia in swine. This study investigated the role of ApxI in hemolysis and cellular damage using a novel apxIA mutant, ApxIA336, which was developed from the parental strain A. pleuropneumoniae serotype 10 that produces only ApxI in vitro. The genotype of ApxIA336 was confirmed by PCR, Southern blotting, and gene sequencing. Exotoxin preparation derived from ApxIA336 was analyzed for its bioactivity towards porcine erythrocytes and alveolar macrophages. Analysis results indicated that ApxIA336 contained a kanamycin-resistant cassette inserted immediately after 1005 bp of the apxIA gene. Phenotype analysis of ApxIA336 revealed no difference in the growth rate as compared to the parental strain. Meanwhile, ApxI production was abolished in the bacterial culture supernatant, i.e. exotoxin preparation. The inability of ApxIA336 to produce ApxI corresponded to the loss of hemolytic and cytotoxic bioactivity in exotoxin preparation, as demonstrated by hemolysis, lactate dehydrogenase release, mitochondrial activity, and apoptosis assays. Additionally, the virulence of ApxIA336 appeared to be attenuated by 15-fold in BALB/c mice. Collectively, ApxI, but not other components in the exotoxin preparation of A. pleuropneumoniae serotype 10, was responsible for the hemolytic and cytotoxic effects on porcine erythrocytes and alveolar macrophages.
Actinobacillus pleuropneumoniae/genetics/*pathogenicity/*physiology ; Animals ; *Apoptosis ; Bacterial Proteins/genetics/metabolism ; Blotting, Southern ; Exotoxins/*genetics ; Hemolysin Proteins/genetics/metabolism ; *Hemolysis ; Macrophages, Alveolar/metabolism/*microbiology ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Swine ; Virulence