Ethyl pyruvate alleviates pulmonary arterial hypertension via PI3K-Akt signaling.

Pulmonary arterial hypertension (PAH) is a pathophysiological syndrome that is extremely difficult to manage, and there is currently no effective treatment. We want to elucidate the therapeutic effect of ethyl pyruvate (EP) on PAH and its possible mechanism. Pulmonary artery endothelial cells (PAECs) were cultured in conventional low-oxygen environments, and cellular proliferation was monitored after treatment with EP. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 was detected by Western blot. After hyperkinetic PAH rabbits' models were treated with EP, hemodynamic data were collected. Right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. Expression of p-PI3K/Akt, LC3-II, and Beclin-1 protein was also detected after using autophagy inhibitor and agonists. We found that EP could inhibit PAECs proliferation. After EP treatment, expression of p-PI3K/Akt was upregulated in vitro and in vivo. LC3-II and Beclin-1 were inhibited and their expression was lower after autophagy inhibitor was given, while after administration of autophagy agonists, their expression was higher than that in the EP alone group. Besides, EP attenuated PAH, and right ventricular hypertrophy and pulmonary vascular remodeling were also reversed. EP can reduce PAH and reverse vascular remodeling which is associated with inhibition of autophagy in PAECs based on PI3K-Akt signaling pathway. The results of this study can provide surgical opportunities for patients with severe PAH caused by congenital heart disease in clinical cardiovascular surgery.

Artificial intelligence automated surgical phases recognition in intraoperative videos of laparoscopic pancreatoduodenectomy.

BACKGROUND: Laparoscopic pancreatoduodenectomy (LPD) is one of the most challenging operations and has a long learning curve. Artificial intelligence (AI) automated surgical phase recognition in intraoperative videos has many potential applications in surgical education, helping shorten the learning curve, but no study has made this breakthrough in LPD. Herein, we aimed to build AI models to recognize the surgical phase in LPD and explore the performance characteristics of AI models. METHODS: Among 69 LPD videos from a single surgical team, we used 42 in the building group to establish the models and used the remaining 27 videos in the analysis group to assess the models' performance characteristics. We annotated 13 surgical phases of LPD, including 4 key phases and 9 necessary phases. Two minimal invasive pancreatic surgeons annotated all the videos. We built two AI models for the key phase and necessary phase recognition, based on convolutional neural networks. The overall performance of the AI models was determined mainly by mean average precision (mAP). RESULTS: Overall mAPs of the AI models in the test set of the building group were 89.7% and 84.7% for key phases and necessary phases, respectively. In the 27-video analysis group, overall mAPs were 86.8% and 71.2%, with maximum mAPs of 98.1% and 93.9%. We found commonalities between the error of model recognition and the differences of surgeon annotation, and the AI model exhibited bad performance in cases with anatomic variation or lesion involvement with adjacent organs. CONCLUSIONS: AI automated surgical phase recognition can be achieved in LPD, with outstanding performance in selective cases. This breakthrough may be the first step toward AI- and video-based surgical education in more complex surgeries.

Delayed gastric emptying after laparoscopic pancreaticoduodenectomy: a single-center experience of 827 cases.

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.

Risk factors of textbook outcome in laparoscopic pancreatoduodenectomy: results from a prospective high-volume center study.

OBJECTIVE: Achieving textbook outcome (TO) implies a smooth recovery post-operation without specified composite complications. This study aimed to evaluate TO in laparoscopic pancreaticoduodenectomy (LPD) and identify independent risk factors associated with achieving TO. METHODS: We conducted a retrospective analysis of data from a randomized controlled trial on LPD at West China Hospital (ChiCTR1900026653). Patients were categorized into the TO and non-TO groups. Perioperative variables were compared between these groups. Multivariate logistic regression was utilized to identify the risk factors. RESULTS: A total of 200 consecutive patients undergoing LPD were included in this study. TO was achieved in 82.5% (n = 165) of the patients. Female patients (OR: 2.877, 95% CI: 1.219-6.790; P = 0.016) and those with a hard pancreatic texture (OR: 2.435, 95% CI: 1.018-5.827; P = 0.046) were associated with an increased likelihood of achieving TO. CONCLUSIONS: TO can be achieved in more than 80% of patients in a high-volume LPD center. Independent risk factors associated with achieving TO included gender (male) and pancreatic texture (soft).

Ultrasound-mediated HGF Gene Microbubbles Mitigate Hyperkinetic Pulmonary Arterial Hypertension in Rabbits.

AIM: Hyperkinetic pulmonary arterial hypertension (PAH) is a complication of congenital heart disease. Gene therapy is a new experimental treatment for PAH, and ultrasound-mediated gene-carrying microbubble targeted delivery is a promising development for gene transfer. METHODS: This study successfully established a hyperkinetic PAH rabbit model by a common carotid artery and jugular vein shunt using the cuff style method. Liposome microbubbles carrying the hepatocyte growth factor (HGF) gene were successfully constructed. An in vitro experiment evaluated the appropriate intensity of ultrasonic radiation by Western blots and 3H-TdR incorporation assays. In an in vivo experiment, after transfection of ultrasound-mediated HGF gene microbubbles, catheterisation was applied to collect haemodynamic data. Hypertrophy of the right ventricle was evaluated by measuring the right ventricle hypertrophy index. Western blot and immunohistochemistry analyses were used to detect the expression of human (h)HGF and angiogenic effects, respectively. RESULTS: The most appropriate ultrasonic radiation intensity was 1.0 W/cm2 for 5 minutes. Two weeks after transfection, both systolic pulmonary arterial pressure and mean pulmonary arterial pressure were attenuated. Hypertrophy of the right ventricle was reversed. hHGF was transplanted into the rabbits, resulting in a high expression of hHGF protein and an increase in the number of small pulmonary arteries. Ultrasound-mediated HGF gene microbubble therapy was more effective at attenuating PAH and increasing the density of small pulmonary arteries than single HGF plasmid transfection. CONCLUSIONS: Ultrasound-mediated HGF gene microbubbles significantly improved the target of gene therapy in a rabbit PAH model and enhanced the tropism and transfection rates. Thus, the technique can effectively promote small pulmonary angiogenesis and play a role in the treatment of PAH without adverse reactions.

A Mendelian randomization-based study of the causal relationship between leisure sedentary behavior and delirium.

BACKGROUND: Delirium is an acute or subacute change in mental status caused by various factors. We evaluated the causal relationship between leisure sedentary behaviors (LSBs) and delirium. METHODS: A two-sample Mendelian randomization (MR) study was performed to evaluate the causal relationship between sedentary behaviors (time spent watching television, time spent using computer, and time spent driving) and delirium. Statistical information for the associations between single nucleotide polymorphisms (SNPs) and the traits of interest was obtained from independent consortia that focused on European populations. The dataset for LSBs was acquired from genome-wide association studies (GWAS) comprising a substantial sample size: 437887 samples for time spent watching television, 360,895 for time spent using computer, and 310,555 for time spent driving. A GWAS with 1269 delirium cases and 209,487 controls was used to identify genetic variation underlying the time of LSBs. We used five complementary MR methods, including inverse variance weighted method (IVW), MR-Egger, weighted median, weighted mode, and simple mode. RESULTS: Genetically predicted time spent watching television (odds ratio [OR]: 2.921, 95 % confidence interval [CI]: 1.381-6.179) demonstrated significant association with delirium (P = 0.005), whereas no significant associations were observed between time spent using computer (OR: 0.556, 95 % CI: 0.246-1.257, P = 0.158) and time spent driving (OR: 1.747, 95 % CI: 0.09-3. 40, P = 0.713) and delirium. Sensitivity analyses supported a causal interpretation, with limited evidence of significant bias from genetic pleiotropy. Moreover, our MR assumptions appeared to be upheld, enhancing the credibility of our conclusions. LIMITATIONS: Larger sample sizes are needed to validate the findings of our study. CONCLUSION: Time spent watching television is a significant risk factor for delirium. Reducing television time may be an important intervention for those at higher risk of delirium.

Suction detection and suction suppression of centrifugal blood pump based on the FFT-GAPSO-LSTM model and speed modulation.

Centrifugal blood pumps are important devices used to treat heart failure. However, they are prone to high-risk suction events that pose a threat to human health when operating at high speeds. To address these issues, a normal suction detection method and a suction suppression method based on the FFT-GAPSO-LSTM model and speed modulation were proposed. The innovation of this suction detection method lies in the application of the genetic particle swarm optimisation (GAPSO) and the fast Fourier transform (FFT) feature extraction method to the long-term and short-term memory (LSTM) model, thereby improving the accuracy of suction detection. After detecting signs of suction, the suction suppression method designed in this study based on variable-speed modulation immediately takes effect, enabling the centrifugal blood pump to quickly return to its normal state by controlling the speed. The suction detection method was divided into four steps. First, a mathematical model of the coupling of the cardiovascular system and the centrifugal blood pump was established, and a real-time blood flow curve was obtained through model simulation. Second, the signal was preprocessed by adding Gaussian white noise and low-pass filtering to make the blood flow signal close to actual working conditions while retaining the original characteristics. Subsequently, through fast Fourier transform (FFT) analysis of the processed curve, the spectral characteristics that can characterise the working state of the centrifugal blood pump were extracted. Finally, the parameters of the LSTM model were optimised using the GAPSO, and the improved LSTM model was used to train and test the blood flow spectrum feature set. The results show that the suction detection method of the FFT-GAPSO-LSTM model can effectively detect whether centrifugal blood pump suction occurs and has certain advantages over other methods. In addition, the simulation results of the suction suppression were excellent and could effectively suppress the occurrence of suction. These results provide a reference for the design of centrifugal blood pump control systems.

Immune dysregulation and macrophage polarization in peri-implantitis.

The term "peri-implantitis" (peri-implantitis) refers to an inflammatory lesion of the mucosa surrounding an endosseous implant and a progressive loss of the peri-implant bone that supports the implant. Recently, it has been suggested that the increased sensitivity of implants to infection and the quick elimination of supporting tissue after infection may be caused by a dysregulated peri-implant mucosal immune response. Macrophages are polarized in response to environmental signals and play multiple roles in peri-implantitis. In peri-implantitis lesion samples, recent investigations have discovered a considerable increase in M1 type macrophages, with M1 type macrophages contributing to the pro-inflammatory response brought on by bacteria, whereas M2 type macrophages contribute to inflammation remission and tissue repair. In an effort to better understand the pathogenesis of peri-implantitis and suggest potential immunomodulatory treatments for peri-implantitis in the direction of macrophage polarization patterns, this review summarizes the research findings related to macrophage polarization in peri-implantitis and compares them with periodontitis.

Interim analysis of short-term outcomes after laparoscopic spleen-preserving distal pancreatectomy with or without preservation of splenic vessels: a randomised controlled trial.

BACKGROUND: Laparoscopic spleen-preserving distal pancreatectomy (LSPDP) is a widely adopted surgical approach for benign and low-grade malignant neoplasms of the distal pancreas. The Kimura and Warshaw techniques represent two principal strategies, yet it still needs to be determined which one is superior. Our investigation aimed to evaluate the clinical outcomes associated with each technique. MATERIALS AND METHODS: This single-center, parallel-group, patient-blinded randomized controlled trial (RCT) was conducted at the XXXXX University. Stratified block randomization was utilized to enroll 114 patients starting in March 2022, with an interim analysis of short-term outcomes scheduled after 45%-50% of participant enrollment. Patients were randomized to receive LSPDP via either the Kimura or Warshaw technique. The primary endpoint was intraoperative blood loss, while secondary endpoints included a range of outcomes from composite outcome to quality of life, as quantified by the EQ-5D-5L. RESULTS: From March 2022 to November 2023, 53 patients were randomly allocated to the Kimura (n=25) or Warshaw (n=28) groups for LSPDP. Baseline characteristics and postoperative outcomes were similar between the groups, such as pancreatic fistula incidence, EQ-5D-5L index scores, and delayed gastric emptying rates. Per-protocol (PP) analysis revealed that the Kimura group experienced significantly less blood loss (52.5±51.6 mL vs. 91.7±113.5 mL, P=0.007) and a reduced rate of composite outcome (23.8% vs. 56.7%, P=0.019), but incurred higher costs in the Warshaw group (¥56,227.4±¥7,027.0 vs. ¥63,513.8±¥12,944.5, P=0.013). Splenic infarction rates were higher in the Warshaw group, though not statistically significant (ITT: 39.3% vs. 12.5%, P=0.058; PP: 36.7% vs. 14.3%, P=0.113), without necessitating intervention. Neither group experienced postpancreatectomy haemorrhage, 90-day mortality, or ICU admissions, and all postoperative complications were mild (Clavien-Dindo Grade