Combined Chemotherapy and Immunotherapy Induction for Screening of Patients with Cervical Esophageal Carcinoma for Subsequent Local Treatment: A New Treatment Paradigm.

BACKGROUND: Definitive chemoradiotherapy is recommended as the primary treatment for cervical esophageal carcinoma (CEC). However, local control rates remain unsatisfactory for some patients. Therefore, in this study, we introduced a new treatment paradigm for individuals with CEC, customizing the choice between subsequent local treatments based on their response to induction chemotherapy and immunotherapy. PATIENTS AND METHODS: Induction treatment comprised two to four cycles of chemotherapy combined with programmed cell death protein 1 (PD-1) inhibitors. Patients achieving complete response (CR) or near CR after induction treatment underwent definitive chemoradiotherapy (dCRT), while those not achieving CR or near CR underwent surgical resection. RESULTS: Among the 40 eligible patients, 14 (35.0%) achieved a CR or near CR after induction treatment. Of the ten patients achieving a CR or near CR, one developed an esophageal fistula after dCRT (10.0%). Among the eight non-CR or non-near CR patients receiving chemoradiotherapy, six developed esophageal fistula (75.0%). Among the 26 patients who did not achieve CR or near CR after induction treatment, the 1-year cancer specific survival (CSS) rates were 93.3% [95% confidence interval (CI) 0.815-1%] for the 18 patients in the surgery group, and 71.4% (95% CI 0.447-1%) for the 8 patients in the chemoradiotherapy group (p = 0.027). The overall laryngeal preservation rate was 85.0% (34/40), with a functional laryngeal preservation rate of 77.5% (31/40). CONCLUSION: The approach consisting of combined immunotherapy and chemotherapy successfully identified patients who were responding well to induction treatment and who were sensitive to radiotherapy, for chemoradiotherapy; thus, improving laryngeal preservation rates. In addition, it also identified patients with poor responses to induction treatment and radiotherapy, for timely surgery; hence, reducing radiotherapy complications and enhancing survival.

Long-Term Survival and Recurrence Patterns in Locally Advanced Esophageal Squamous Cell Carcinoma Patients with Pathologic Complete Response After Neoadjuvant Chemotherapy Followed by Surgery.

BACKGROUND: The higher pathologic complete response (pCR) after neoadjuvant chemoradiotherapy compared with neoadjuvant chemotherapy for locally advanced esophageal squamous cell carcinoma (ESCC) has not translated into significant gains in overall survival. Data on the long-term survival of patients who obtained a pCR after neoadjuvant chemotherapy are scarce. Therefore, this study aimed to evaluate the long-term prognosis and recurrence patterns in these patients. METHODS: The study enrolled patients with locally advanced ESCC after neoadjuvant chemotherapy followed by surgery in the authors' hospital between January 2007 and December 2020. The factors predictive of pCR were analyzed. Furthermore, propensity score-matching was performed for those who did and those who did not have a pCR using 1:5 ratio for a long-term survival analysis. Finally, the survival and recurrence patterns of patients obtaining pCR after neoadjuvant chemotherapy were analyzed. RESULTS: A pCR was achieved for 61 (8.70%) of the 701 patients in the study. Univariate analysis showed that the patients without alcohol drinking had a higher possibility of obtaining a pCR, although multivariate analysis failed to confirm the difference as significant. After propensity score-matching, the 5-year overall survival was 84.50% for the patients who had a pCR and 52.90% for those who did not (p < 0.001). Among the 61 patients with a pCR, 9 patients (14.80%) experienced recurrence, including 6 patients with locoregional recurrence and 3 patients with distant metastasis. CONCLUSION: Advanced ESCC patients with pCR after neoadjuvant chemotherapy had a favorable prognosis, yet some still experienced recurrence, particularly locoregional recurrence. Therefore, for this group of patients, regular follow-up evaluation also is needed.

URP20 improves corneal injury caused by alkali burns combined with pathogenic bacterial infection in rats.

Corneal alkali burns often occur in industrial production and daily life, combined with infection, and may cause severe eye disease. Oxidative stress and neovascularization (NV) are important factors leading to a poor prognosis. URP20 is an antimicrobial peptide that has been proven to treat bacterial keratitis in rats through antibacterial and anti-NV effects. Therefore, in this study, the protective effect and influence mechanism of URP20 were explored in a rat model of alkali burn together with pathogenic bacteria (Staphylococcus aureus and Escherichia coli) infection. In addition, human umbilical vein endothelial cells (HUVECs) and human corneal epithelial cells (HCECs) were selected to verify the effects of URP20 on vascularization and oxidative stress. The results showed that URP20 treatment could protect corneal tissue, reduce corneal turbidity, and reduce the NV pathological score. Furthermore, URP20 significantly inhibited the expression of the vascularization marker proteins VEGFR2 and CD31. URP20 also reduced the migration ability of HUVECs. In terms of oxidative stress, URP20 significantly upregulated SOD and GSH contents in corneal tissue and HCECs (treated with 200 µM H2O2) and promoted the expression of the antioxidant protein Nrf2/HO-1. At the same time, MDA and ROS levels were also inhibited. In conclusion, URP20 could improve corneal injury combined with bacterial infection in rats caused by alkali burns through antibacterial, anti-NV, and antioxidant activities.

miR-200a-3p inhibits the PDGF-BB-induced proliferation of VSMCs by affecting their phenotype-associated proteins.

Accumulating evidence shows that the abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) can significantly affect the long-term prognosis of coronary artery bypass grafting. This study aimed to explore the factors affecting the proliferation, migration, and phenotypic transformation of VSMCs. First, we stimulated VSMCs with different platelet-derived growth factor-BB (PDGF-BB) concentrations, analyzed the expression of phenotype-associated proteins by Western blotting, and examined cell proliferation by scratch wound healing and the 5-ethynyl-2-deoxyuridine (EdU) assay. VSMC proliferation was induced most by PDGF-BB treatment at 20 ng/mL. miR-200a-3p decreased significantly in A7r5 cells stimulated with PDGF-BB. The overexpression of miR-200a-3p reversed the downregulation of α-SMA (p < 0.001) and the upregulation of vimentin (p < 0.001) caused by PDGF-BB. CCK8 and EdU analyses showed that miR-200a-3p overexpression could inhibit PDGF-BB-induced cell proliferation (p < 0.001). However, flow cytometric analysis showed that it did not significantly increase cell apoptosis. Collectively, the overexpression of miR-200a-3p inhibited the proliferation and migration of VSMCs induced by PDGF-BB, partly by affecting phenotypic transformation-related proteins, providing a new strategy for relieving the restenosis of vein grafts.

Structural and functional insights into the epigenetic regulator MRG15.

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.

Quantitative imaging for predicting hematoma expansion in intracerebral hemorrhage: A multimodel comparison.

BACKGROUND: Several studies report that radiomics provides additional information for predicting hematoma expansion in intracerebral hemorrhage (ICH). However, the comparison of diagnostic performance of radiomics for predicting revised hematoma expansion (RHE) remains unclear. METHODS: The cohort comprised 312 consecutive patients with ICH. A total of 1106 radiomics features from seven categories were extracted using Python software. Support vector machines achieved the best performance in both the training and validation datasets. Clinical factors models were constructed to predict RHE. Receiver operating characteristic curve analysis was used to assess the abilities of non-contrast computed tomography (NCCT) signs, radiomics features, and combined models to predict RHE. RESULTS: We finally selected the top 21 features for predicting RHE. After univariate analysis, 4 clinical factors and 5 NCCT signs were selected for inclusion in the prediction models. In the training and validation dataset, radiomics features had a higher predictive value for RHE (AUC = 0.83) than a single NCCT sign and expansion-prone hematoma. The combined prediction model including radiomics features, clinical factors, and NCCT signs achieved higher predictive performances for RHE (AUC = 0.88) than other combined models. CONCLUSIONS: NCCT radiomics features have a good degree of discrimination for predicting RHE in ICH patients. Combined prediction models that include quantitative imaging significantly improve the prediction of RHE, which may assist in the risk stratification of ICH patients for anti-expansion treatments.

SARS-CoV-2 hijacks macropinocytosis to facilitate its entry and promote viral spike-mediated cell-to-cell fusion.

Revealing the mechanisms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry and cell-to-cell spread might provide insights for understanding the underlying mechanisms of viral pathogenesis, tropism, and virulence. The signaling pathways involved in SARS-CoV-2 entry and viral spike-mediated cell-to-cell fusion remain elusive. In the current study, we found that macropinocytosis inhibitors significantly suppressed SARS-CoV-2 infection at both the entry and viral spike-mediated cell-to-cell fusion steps. We demonstrated that SARS-CoV-2 entry required the small GTPase Rac1 and its effector kinase p21-activated kinase 1 by dominant-negative and RNAi assays in human embryonic kidney 293T-angiotensin-converting enzyme 2 cells and that the serine protease transmembrane serine protease 2 reversed the decrease in SARS-CoV-2 entry caused by the macropinocytosis inhibitors. Moreover, in the cell-to-cell fusion assay, we confirmed that macropinocytosis inhibitors significantly decreased viral spike-mediated cell-to-cell fusion. Overall, we provided evidence that SARS-CoV-2 utilizes a macropinocytosis pathway to enter target cells and to efficiently promote viral spike-mediated cell-to-cell fusion.

A systematic review and meta-analysis on the prevalence of stigma in infectious diseases, including COVID-19: a call to action.

Infectious diseases, including COVID-19, are crucial public health issues and may lead to considerable fear among the general public and stigmatization of, and discrimination against, specific populations. This meta-analysis aimed to estimate the pooled prevalence of stigma in infectious disease epidemics. We systematically searched PubMed, PsycINFO, Embase, MEDLINE, Web of Science, and Cochrane databases since inception to June 08, 2021, and reported the prevalence of stigma towards people with infectious diseases including SARS, H1N1, MERS, Zika, Ebola, and COVID-19. A total of 50 eligible articles were included that contributed 51 estimates of prevalence in 92722 participants. The overall pooled prevalence of stigma across all populations was 34% [95% CI: 28-40%], including enacted stigma (36% [95% CI: 28-44%]) and perceived stigma (31% [95% CI: 22-40%]). The prevalence of stigma in patients, community population, and health care workers, was 38% [95% CI: 12- 65%], 36% [95% CI: 28-45%], and 30% [95% CI: 20-40%], respectively. The prevalence of stigma in participants from low- and middle-income countries was 37% [95% CI: 29-45%], which is higher than that from high-income countries (27% [95% CI: 18-36%]) though this difference was not statistically significant. A similar trend of prevalence of stigma was also observed in individuals with lower education (47% [95% CI: 23-71%]) compared to higher education level (33% [95% CI: 23-4%]). These findings indicate that stigma is a significant public health concern, and effective and comprehensive interventions are needed to counteract the damaging effects of the infodemics during infectious disease epidemics, including COVID-19, and reduce infectious disease-related stigma.

A systematic review and meta-analysis on prevalence of and risk factors associated with depression, anxiety and insomnia in infectious diseases, including COVID-19: a call to action.

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.

Prognostic impact of new permanent pacemaker implantation following transcatheter aortic valve replacement.

BACKGROUND: Conduction disturbances requiring permanent pacemaker implantation (PPI) are common following transcatheter aortic valve replacement (TAVR). There were conflicting data regarding the impact of new PPI on clinical outcomes after TAVR. OBJECTIVES: The study sought to evaluate the impact of new PPI on clinical outcomes in patients undergoing TAVR. METHODS: This study was a retrospective analysis of prospectively collected data. Data were from 210 consecutive patients without prior PPI who underwent TAVR due to severe symptomatic aortic stenosis at our center between June 2018 and July 2020. Clinical, echocardiographic, and pacing data were assessed at 30-day, 1- and 2-year follow-up. RESULTS: New PPI was required in 35 (16.7%) patients within 30 days after TAVR. The median time from TAVR to PPI was 3 days. The most common indication for PPI was high-degree or complete atrioventricular block. The median follow-up was 798.0 (interquartile range, 669.0-1115.0) days. There were no differences in all-cause mortality (adjusted hazard ratio [HR]: 1.18; 95% confidence interval [CI]: 0.85-2.36; p = 0.415) and cardiovascular mortality (adjusted HR: 0.92; 95% CI: 0.57-1.89; p = 0.609) between groups. However, PPI group had a higher risk of heart failure (HF) rehospitalization (adjusted HR: 1.53; 95% CI: 1.26-2.28; p = 0.027). Echocardiography showed no significant improvement of LVEF over time in patients with PPI. At the latest follow-up, 31.3% of patients exhibited low (≤10%) pacing burdens, whereas 28.1% of patients had near constant (>90%) right ventricular pacing. CONCLUSIONS: New PPI within 30 days following TAVR was not associated with an increased risk of all-cause or cardiovascular mortality. However, patients with PPI had a higher risk of HF rehospitalization and lack of LVEF improvement.

Klf5 down-regulation induces vascular senescence through eIF5a depletion and mitochondrial fission.

Although dysregulation of mitochondrial dynamics has been linked to cellular senescence, which contributes to advanced age-related disorders, it is unclear how Krüppel-like factor 5 (Klf5), an essential transcriptional factor of cardiovascular remodeling, mediates the link between mitochondrial dynamics and vascular smooth muscle cell (VSMC) senescence. Here, we show that Klf5 down-regulation in VSMCs is correlated with rupture of abdominal aortic aneurysm (AAA), an age-related vascular disease. Mice lacking Klf5 in VSMCs exacerbate vascular senescence and progression of angiotensin II (Ang II)-induced AAA by facilitating reactive oxygen species (ROS) formation. Klf5 knockdown enhances, while Klf5 overexpression suppresses mitochondrial fission. Mechanistically, Klf5 activates eukaryotic translation initiation factor 5a (eIF5a) transcription through binding to the promoter of eIF5a, which in turn preserves mitochondrial integrity by interacting with mitofusin 1 (Mfn1). Accordingly, decreased expression of eIF5a elicited by Klf5 down-regulation leads to mitochondrial fission and excessive ROS production. Inhibition of mitochondrial fission decreases ROS production and VSMC senescence. Our studies provide a potential therapeutic target for age-related vascular disorders.

Investigation of the mechanical and transport properties of InGeX3 (X = S, Se and Te) monolayers using density functional theory and machine learning.

Recently, novel 2D InGeTe3 has been successfully synthesized and attracted attention due to its excellent properties. In this study, we investigated the mechanical properties and transport behavior of InGeX3 (X = S, Se and Te) monolayers using density functional theory (DFT) and machine learning (ML). The key physical parameters related to mechanical properties, including Poisson's ratio, elastic modulus, tensile strength and critical strain, were revealed. Using a ML method to train DFT data, we developed a neuroevolution-potential (NEP) to successfully predict the mechanical properties and lattice thermal conductivity. The fracture behavior predicted using NEP-based MD simulations in a large supercell containing 20 000 atoms could be verified using DFT. Due to the effects of size, these predicted physical parameters have a slight difference between DFT and ML methods. At 300 K, these monolayers exhibited a low thermal conductivity with the values of 13.27 ± 0.24 W m-1 K-1 for InGeS3, 7.68 ± 0.30 W m-1 K-1 for InGeSe3, and 3.88 ± 0.09 W m-1 K-1 for InGeTe3, respectively. The Boltzmann transport equation (BTE) including all electron-phonon interactions was used to accurately predict the electron mobility. Compared with InGeS3 and InGeSe3, the InGeTe3 monolayer showed flexible mechanical behavior, low thermal conductivity and high mobility.

Transfemoral transcatheter aortic valve replacement for pure native aortic regurgitation: one-year outcomes of a single-center study.

BACKGROUND: Evidence about safety and efficacy of transcatheter aortic valve replacement (TAVR) with the Venus A-Valve system (Venus Medtech, Hangzhou, China) remains limited for patients with pure native aortic regurgitation (PNAR). OBJECTIVES: The single-center study sought to report the one-year clinical outcomes of the Venus A-Valve in the treatment of PNAR. METHODS: This study was a retrospective analysis of prospectively collected data. Data was from all consecutive patients who had PNAR and underwent TAVR with the Venus A-Valve system at our center from July 2020 and June 2021. Procedural and clinical outcomes up to one year were analyzed using Valve Academic Research Consortium-2 criteria. RESULTS: A total of 45 consecutive patients with PNAR underwent transfemoral TAVR with the Venus A-Valve system. The Mean age was 73.5 ± 5.5 years and 26.7% were female. All the TAVR procedures were performed via transfemoral access. Implantations were successful in 44 cases (97.8%). Only one patient was converted to surgical aortic valve replacement. No patient died intraoperatively. No second valve was implanted. In-hospital mortality rate was 2.3%. The one-year all-cause mortality rate was 4.7% without cardiovascular related death. No patient had moderate or severe paravalvular leakage during follow-up. At one year, the mean pressure gradient was 8.8 ± 0.9 mmHg, and left ventricular ejection fraction increased to 61.5 ± 3.6%. CONCLUSIONS: This single-center study demonstrated the safety and efficacy of transfemoral TAVR with the Venus A-Valve in the treatment of patients with PNAR.

Effect of Different Administration Routes of Dexmedetomidine on Postoperative Delirium in Elderly Patients Undergoing Elective Spinal Surgery: A Prospective Randomized Double-Blinded Controlled Trial.

BACKGROUND: Intravenous dexmedetomidine has been reported to decrease the occurrence of postoperative delirium (POD) in elderly patients. Nevertheless, some previous studies have indicated that intratracheal dexmedetomidine and intranasal dexmedetomidine are also effective and convenient. The current study aimed to compare the effect of different administration routes of dexmedetomidine on POD in elderly patients. METHODS: We randomly allocated 150 patients (aged 60 years or more) scheduled for spinal surgery to receive intravenous dexmedetomidine (0.6 µg/kg), intranasal dexmedetomidine (1 µg/kg) before anesthesia induction, or intratracheal dexmedetomidine (0.6 µg/kg) after anesthesia induction. The primary outcome was the frequency of delirium during the first 3 postoperative days. The secondary outcomes were the incidence of postoperative sore throat (POST) and sleep quality. Adverse events were recorded, and routine treatment was performed. RESULTS: Compared with the intranasal group, the intravenous group had a significantly lower occurrence of POD within 3 days (3 of 49 [6.1%] vs 14 of 50 [28.0%]; odds ratio [OR], 0.17; 95% confidence intervals [CIs], 0.05-0.63; P < .017). Meanwhile, patients in the intratracheal group had a lower incidence of POD than those in the intranasal group (5 of 49 [10.2%] vs 14 of 50 [28.0%]; OR, 0.29; 95% CI, 0.10-0.89; P < .017). Whereas, there was no difference between the intratracheal and intravenous groups (5 of 49 [10.2%] vs 3 of 49 [6.1%]; OR, 1.74; 95% CI, 0.40-7.73; P > .017). The rate of POST was lower in the intratracheal group than that in the other 2 groups at 2 hours after surgery (7 of 49 [14.3%] vs 12 of 49 [24.5%] vs 18 of 50 [36.0%], P < .017, respectively). Intravenous dexmedetomidine had the lowest Pittsburgh Sleep Quality Index score on the second morning after surgery (median [interquartile range {IQR}]: 4 [3-5] vs 6 [4-7] vs 6 [4-7], P < .017, respectively). Compared with the intranasal group, the intravenous group had a higher rate of bradycardia and a lower incidence of postoperative nausea and vomiting ( P < .017). The intranasal group was associated with the highest incidence of hypertension ( P < .017). CONCLUSIONS: For patients aged ≥60 years undergoing spinal surgery, compared with the intranasal route of dexmedetomidine, intravenous and intratracheal dexmedetomidine reduced the incidence of early POD. Meanwhile, intravenous dexmedetomidine was associated with better sleep quality after surgery, and intratracheal dexmedetomidine resulted in a lower incidence of POST. Adverse events were mild in all 3 administration routes of dexmedetomidine.

Radially polarized beams' phase filtering focal properties based on path integral analysis.

This paper introduces the path integral (PI) to the analysis of radially polarized (RP) beams' tight focusing problem. The PI makes the contribution of each incident ray on the focal region visible and then makes it possible to choose the filter's parameters more intuitively and precisely. Based on the PI, a zero point construction (ZPC) phase filtering method is realized intuitively. With ZPC, the focal properties of RP solid and annular beams before and after filtering were analyzed. The results show that the combination of a large NA annular beam and phase filtering can result in superior focus properties.

Comparative Efficacy and Safety of Thrombolytic Agents for Pulmonary Embolism: A Bayesian Network Meta-Analysis.

BACKGROUND: Thrombolytic agents and anticoagulants are the two classes of medication used in the treatment of acute pulmonary embolism (PE). There is continuous renewal and iteration of thrombolytic agents, and the efficacy and adverse effects of different agents have different effects on PE due to their different mechanisms of action. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of different thrombolytic agents in the treatment of all types of acute PE: hemodynamically unstable PE (massive PE) and hemodynamically stable PE (submassive PE and low-risk PE), using a network meta-analysis. METHODS: A search was conducted of the following databases: PubMed, The Cochrane Library, Embase, and Web of Science to collect randomized controlled trials (RCTs) comparing thrombolytic agents with heparin or other thrombolytic agents in patients with acute PE; the clinical outcomes included patient mortality, recurrent PE, pulmonary artery systolic pressure (PASP) after treatment, and major and minor bleeding. The measurement duration of outcome indicators was the longest follow-up period. Thereafter, a network meta-analysis was performed using a Bayesian network framework. RESULTS: A total of 29 RCTs (3,067 patients) were included, of which 6 studies (304 patients) were massive PE, 14 studies (2,173 patients) were submassive PE, 1 study (83 patients) included massive and submassive PE, and 8 studies (507 patients) were PE of unknown type. The treatment regimens included thrombolytic therapy (alteplase, reteplase, tenecteplase, streptokinase, and urokinase) and anticoagulant therapy alone. The results showed that the mortality using thrombolytic agents (except tenecteplase) was significantly lower compared with heparin. The recurrence of PE with alteplase was significantly lower compared with heparin (RR = 0.23, 95% CI, 0.04, 0.65). The PASP after using alteplase was significantly lower compared with heparin (mean difference = -11.36, 95% CI, -21.45, -1.56). Compared with heparin, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.27, 95% CI, 1.36, 7.39); compared with streptokinase, the incidence of minor bleeding associated with tenecteplase was higher (RR = 3.22, 95% CI, 1.01, 11.10). CONCLUSION: For patients with acute PE, four thrombolytic agents (alteplase, reteplase, streptokinase, and urokinase) appeared to be superior in efficacy compared with anticoagulants alone due to a reduction in mortality and no increase in bleeding risk. Alteplase may be a better choice because it not only reduced mortality but also reduced PE recurrence rate and treated PASP. Tenecteplase did not reduce mortality compared with anticoagulants alone and may not be a good choice of thrombolytic agent due to an increase in minor bleeding compared with streptokinase and anticoagulants alone. Thrombolytic drugs should be rationally selected to optimize the thrombolytic regimen and achieve as good a balance as possible between thrombolysis and bleeding.

Pre-operative oil ingestion reduces the probability of thoracic duct trunk ligation during esophagectomy.

Chylothorax is an important complication after esophagectomy. Ligation of the injured thoracic duct is the main method to prevent chylothorax after esophagectomy, but may be associated with adverse effects. Whether ligation of the injured tributary alone, keeping the main trunk intact, may suffice to prevent post-operative chylothorax is not well known. Since March 2017, 40 mL of olive oil was administered to patients posted for esophagectomy. We compared patients admitted between March 2017 and December 2019 with patients admitted between July 2014 and February 2017, who had not received pre-operative oil. The outcome measures were the need for thoracic duct main trunk or tributary ligation, development of chylothorax and missed ligation. There were 371 patients in the oil ingestion group and 308 patients in the standard control group. Chylothorax in the oil ingestion group was significantly lower than that in the standard control group (1.3% vs. 4.5%, P = 0.012). Chyle leak from thoracic duct tributaries was diagnosed in a significantly higher percentage (5.7% vs. 0.0%, P < 0.001) and missed ligation of the injured thoracic duct was significantly lower (0.3% vs. 3.9%, P = 0.002) in the oil ingestion group compared with the standard control group. The incidence of post-operative chylothorax was not statistically different (6.3% vs. 10.0%, P = 1.000) between the tributary and the trunk ligation group. Pre-operative oil ingestion can help visualize the thoracic duct trunk and its tributaries during esophagectomy. Thus, non-selected thoracic duct trunk ligation and missed ligation during esophagectomy can be reduced. Precise ligation of the injured tributary while the main trunk is intact can also prevent post-operative chylothorax.

The Role of the Cerebellum in Drug Reward: A Review.

Drug abuse remains a global problem; nonetheless, its mechanism has not yet been fully understood. Recent studies have reported on the non-motor functions of the cerebellum, and evidence from neuroimaging and behavioral studies has suggested the role of cerebellum in drug reward, which has received increasing attention. Furthermore, emerging technological developments have aided in clarifying the various circuits and functions of the cerebellum. Exploring the role of the cerebellum in drug reward can improve our understanding of the mechanism underlying addiction and facilitate the development of new treatment schemes. This review summarizes the anatomy of the cerebellum and its connections to brain regions considered important in addiction. Subsequently, we investigate the neurological reasons elucidating why the cerebellum is a potential target for drug reward. Additionally, we expound the molecular targets of addictive drugs in the cerebellum, mainly glutamate and endocannabinoids. Unlike previous studies, this article focuses on the influence of alcohol, nicotine, morphine, cannabis, and cocaine on the cerebellum from multiple viewpoints, including imaging and behavioral changes, molecular signals, neurotransmitters, and synaptic transmission. We aim to clarify some drug-induced cerebellar changes to supplement the previous research regarding the relationship between addiction and the cerebellum. Finally, we discuss the limitations and prospects of drug reward research on the cerebellum to provide novel insights into studying the cerebellum and its role in addiction. We recommend that future addiction network models should include the cerebellum to provide new therapeutic targets for treating addiction.

20(S)-protopanaxatriol inhibited D-galactose-induced brain aging in mice via promoting mitochondrial autophagy flow.

Previous reports have confirmed that saponins (ginsenosides) derived from Panax ginseng. C. A. Meyer exerted obvious memory-enhancing and antiaging effects, and the simpler the structure of ginsenosides, the better the biological activity. In this work, we aimed to explore the therapeutic effect and underlying molecular mechanism of 20(S)-protopanaxatriol (PPT), the aglycone of panaxatriol-type ginsenosides, by establishing D-galactose (D-gal)-induced subacute brain aging model in mice. The results showed that PPT treatment (10 and 20 mg/kg) for 4 weeks could significantly restore the D-gal (800 mg/kg for 8 weeks)-induced impaired memory function, choline dysfunction, and redox system imbalance in mice. Meanwhile, PPT also significantly reduced the histopathological changes caused by D-gal exposure. Moreover, PPT could increase TFEB/LAMP2 protein expression to promote mitochondrial autophagic flow. Importantly, the results from molecular docking showed that PPT had good binding ability with LAMP2 and TFEB, suggesting that TFEB/LAMP2 might play an important role in PPT to alleviate D-gal-caused brain aging.

The Application of Computer Technology to Clinical Practice Guideline Implementation: A Scoping Review.

Implementation of clinical practice guidelines (CPG) is a complex and challenging task. Computer technology, including artificial intelligence (AI), has been explored to promote the CPG implementation. This study has reviewed the main domains where computer technology and AI has been applied to CPG implementation. PubMed, Embase, Web of science, the Cochrane Library, China National Knowledge Infrastructure database, WanFang DATA, VIP database, and China Biology Medicine disc database were searched from inception to December 2021. Studies involving the utilization of computer technology and AI to promote the implementation of CPGs were eligible for review. A total of 10429 published articles were identified, 117 met the inclusion criteria. 21 (17.9%) focused on the utilization of AI techniques to classify or extract the relative content of CPGs, such as recommendation sentence, condition-action sentences. 47 (40.2%) focused on the utilization of computer technology to represent guideline knowledge to make it understandable by computer. 15 (12.8%) focused on the utilization of AI techniques to verify the relative content of CPGs, such as conciliation of multiple single-disease guidelines for comorbid patients. 34 (29.1%) focused on the utilization of AI techniques to integrate guideline knowledge into different resources, such as clinical decision support systems. We conclude that the application of computer technology and AI to CPG implementation mainly concentrated on the guideline content classification and extraction, guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration. The AI methods used for guideline content classification and extraction were pattern-based algorithm and machine learning. In guideline knowledge representation, guideline knowledge verification, and guideline knowledge integration, computer techniques of knowledge representation were the most used.