Applying improved ddPCR to reliable quantification of MPXV in clinical settings.

Monkeypox virus (MPXV) poses a global health threat. Droplet digital PCR (ddPCR) holds potential as an accurate diagnostic tool for clinical microbiology. However, there is limited literature on the applicability of ddPCR in clinical settings. In this study, the clinical features of patients with MPXV during the initial outbreak in China in June 2023 were reviewed, and an optimized ddPCR method with dilution and/or inhibitor removal was developed to enhance MPXV detection efficiency. Eighty-two MPXV samples were tested from nine different clinical specimen types, including feces, urine, pharyngeal swabs, anal swabs, saliva, herpes fluid, crust, and semen, and the viral load of each specimen was quantified. A comparative analysis was performed with qPCR to assess sensitivity and specificity and to investigate the characteristics of MPXV infection by analyzing viral loads in different clinical specimens. Consequently, common pharyngeal and gastrointestinal symptoms were observed in patients with MPXV. The optimized ddPCR method demonstrated relatively high sensitivity for MPXV quantification in the clinical materials, with a limit of detection of 0.1 copies/µL. This was particularly evident in low-concentration samples like whole blood, semen, and urine. The optimized ddPCR demonstrated greater detection accuracy compared with normal ddPCR and qPCR, with an area under the curve (AUC) of 0.939. Except for crust samples, viral loads in the specimens gradually decreased as the disease progressed. Virus levels in feces and anal swabs kept a high detection rate at each stage of post-symptom onset, and feces and anal swabs samples may be suitable for clinical diagnosis and continuous monitoring of MPXV. IMPORTANCE: The ddPCR technique proved to be a sensitive and valuable tool for accurately quantifying MPXV viral loads in various clinical specimen types. The findings provided valuable insights into the necessary pre-treatment protocols for MPXV diagnosis in ddPCR detection and the potentially suitable sample types for collection. Therefore, such results can aid in comprehending the potential characteristics of MPXV infection and the usage of ddPCR in clinical settings.

Availability and threshold of the vasoactive-inotropic score for predicting early extubation in adults after rheumatic heart valve surgery: a single-center retrospective cohort study.

BACKGROUND: Early extubation (EEx) is defined as the removal of the endotracheal tube within 8 h postoperatively. The present study involved determining the availability and threshold of the vasoactive-inotropic score (VIS) for predicting EEx in adults after elective rheumatic heart valve surgery. METHODS: The present study was designed as a single-center retrospective cohort study which was conducted with adults who underwent elective rheumatic heart valve surgery with CPB. The highest VIS in the immediate postoperative period was used in the present study. The primary outcome, the availability of VIS for EEx prediction and the optimal threshold value were determined using ROC curve analysis. The gray zone analysis of the VIS was performed by setting the false negative or positive rate R = 0.05, and the perioperative risk factors for prolonged EEx were identified by multivariate logistic analysis. The postoperative complications and outcomes were compared between different VIS groups. RESULTS: Among the 409 patients initially screened, 379 patients were ultimately included in the study. The incidence of EEx was determined to be 112/379 (29.6%). The VIS had a good predictive value for EEx (AUC = 0.864, 95% CI: [0.828, 0.900], P < 0.001). The optimal VIS threshold for EEx prediction was 16.5, with a sensitivity of 71.54% (65.85-76.61%) and a specificity of 88.39% (81.15-93.09%). The upper and lower limits of the gray zone for the VIS were determined as (12, 17.2). The multivariate logistic analysis identified age (OR, 1.060; 95% CI: 1.017-1.106; P = 0.006), EF% (OR, 0.798; 95% CI: 0.742-0.859; P < 0.001), GFR (OR, 0.933; 95% CI: 0.906-0.961; P < 0.001), multiple valves surgery (OR, 4.587; 95% CI: 1.398-15.056; P = 0.012), and VIS > 16.5 (OR, 12.331; 95% CI: 5.015-30.318; P < 0.001) as the independent risk factors for the prolongation of EEx. The VIS ≤ 16.5 group presented a greater success rate for EEx, a shorter invasive ventilation support duration, and a lower incidence of complications than did the VIS > 16.5 group, while the incidence of reintubation was similar between the two groups. CONCLUSION: In adults, after elective rheumatic heart valve surgery, the highest VIS in the immediate postoperative period was a good predictive value for EEx, with a threshold of 16.5.

Ginkgolide B can alleviate spinal cord glymphatic system dysfunction and provide neuroprotection in painful diabetic neuropathy rats by inhibiting matrix metalloproteinase-9.

The glymphatic system plays a crucial role in maintaining optimal central nervous system (CNS) function by facilitating the removal of metabolic wastes. Aquaporin-4 (AQP4) protein, predominantly located on astrocyte end-feet, is a key pathway for metabolic waste excretion. ß-Dystroglycan (ß-DG) can anchor AQP4 protein to the end-feet membrane of astrocytes and can be cleaved by matrix metalloproteinase (MMP)-9 protein. Studies have demonstrated that hyperglycemia upregulates MMP-9 expression in the nervous system, leading to neuropathic pain. Ginkgolide B (GB) exerts an inhibitory effect on the MMP-9 protein. In this study, we investigated whether inhibition of MMP-9-mediated ß-DG cleavage by GB is involved in the regulation of AQP4 polarity within the glymphatic system in painful diabetic neuropathy (PDN) and exerts neuroprotective effects. The PDN model was established by injecting streptozotocin (STZ). Functional changes in the glymphatic system were observed using magnetic resonance imaging (MRI). The paw withdrawal threshold (PWT) was measured to assess mechanical allodynia. The protein expressions of MMP-9, ß-DG, and AQP4 were detected by Western blotting and immunofluorescence. Our findings revealed significant decreases in the efficiency of contrast agent clearance within the spinal glymphatic system of the rats, accompanied by decreased PWT, increased MMP-9 protein expression, decreased ß-DG protein expression, and loss of AQP4 polarity. Notably, GB treatment demonstrated the capacity to ameliorate spinal cord glymphatic function by modulating AQP4 polarity through MMP-9 inhibition, offering a promising therapeutic avenue for PDN.

Effect of deep neuromuscular block on the quality of early recovery after sleeve gastrectomy in obese patients: a randomized controlled trial.

BACKGROUND: Deep neuromuscular block (NMB) has been shown to improve surgical conditions and alleviate post-operative pain in bariatric surgery compared with moderate NMB. We hypothesized that deep NMB could also improve the quality of early recovery after laparoscopic sleeve gastrectomy (LSG). METHODS: Eighty patients were randomized to receive either deep (post-tetanic count 1-3) or moderate (train-of-four count 1-3) NMB. The QoR-15 questionnaire was used to evaluate the quality of early recovery at 1 day before surgery (T0), 24 and 48 h after surgery (T2, T3). Additionally, we recorded diaphragm excursion (DE), postoperative pain, surgical condition, cumulative dose of analgesics, time of first flatus and ambulation, post-operative nausea and vomiting, time of tracheal tube removal and hospitalization time. MAIN RESULTS: The quality of recovery was significantly better 24 h after surgery in patients who received a deep versus moderate block (114.4 ± 12.9 versus 102.1 ± 18.1). Diaphragm excursion was significantly greater in the deep NMB group when patients performed maximal inspiration at T2 and T3 (P < 0.05). Patients who underwent deep NMB reported lower visceral pain scores 40 min after surgery; additionally, these patients experienced lower pain during movement at T3 (P < 0.05). Optimal surgical conditions were rated in 87.5% and 64.6% of all measurements during deep and moderate NMB respectively (P < 0.001). The time to tracheal tube removal was significantly longer in the deep NMB group (P = 0.001). There were no differences in other outcomes. CONCLUSION: In obese patients receiving deep NMB during LSG, we observed improved QoR-15 scores, greater diaphragmatic excursions, improved surgical conditions, and visceral pain scores were lower. More evidence is needed to determine the effects of deep NMB on these outcomes. TRIAL REGISTRATION: ChiCTR2200065919. Date of retrospectively registered: 18/11/2022.

RNA binding motif 4 inhibits the replication of ebolavirus by directly targeting 3'-leader region of genomic RNA.

Ebola virus (EBOV) belongs to Filoviridae family possessing single-stranded negative-sense RNA genome, which is a serious threat to human health. Nowadays, no therapeutics have been proven to be successful in efficiently decreasing the mortality rate. RNA binding proteins (RBPs) are reported to participate in maintaining cell integrity and regulation of viral replication. However, little is known about whether and how RBPs participate in regulating the life cycle of EBOV. In our study, we found that RNA binding motif protein 4 (RBM4) inhibited the replication of EBOV in HEK293T and Huh-7 cells by suppressing viral mRNA production. Such inhibition resulted from the direct interaction between the RRM1 domain of RBM4 and the "CU" enrichment elements located in the PE1 and TSS of the 3'-leader region within the viral genome. Simultaneously, RBM4 could upregulate the expression of some cytokines involved in the host innate immune responses to synergistically exert its antiviral function. The findings therefore suggest that RBM4 might serve as a novel target of anti-EBOV strategy.

Fish oil omega-3 Fatty Acids Alleviate Postoperative delirium-like Behavior in aged mice by Attenuating Neuroinflammation and Oxidative Stress.

Postoperative delirium (POD) is a common and serious neuropsychiatric syndrome among older patients, and lacks effective therapies. Omega-3 fatty acids, possessing anti-inflammatory and antioxidant properties, have shown potent neuroprotective effects in several diseases. The present study investigated whether omega-3 fatty acids could exert a neuroprotective role against POD in aged mice. A mouse model of POD was established to explore the role of omega-3 fatty acids in laparotomy-induced delirium-like behavior by evaluating systemic inflammatory changes, neuroinflammation, oxidative stress, and behavior at different time points in aged mice. Oral gavage with omega-3 fatty acids (300 mg/kg) for 3 weeks before surgery significantly attenuated anesthesia/surgery-induced POD-like behavior and the accumulation of proinflammatory cytokines from the peripheral blood in aged mice. Moreover, it also remarkably mitigated neuroinflammation and the oxidative stress response (malondialdehyde [MDA] and superoxide dismutase [SOD]) in the prefrontal cortex and hippocampus of surgical mice. Our findings provided evidence that pretreatment with omega-3 fatty acids may play a vital role in the treatment of POD through mechanisms involving its anti-inflammatory and antioxidant effects, which may be a promising prevention strategy for POD in aged patients.

A retrospective study on the relationship between 5 modified frailty index (5-mFI) and postoperative complications of gynecological elderly patients undergoing abdominal surgery.

INTRODUCTION: Aim to evaluate the application of 5 modified frailty index (5-mFI) in predicting postoperative complications in elderly gynecological patients undergoing abdominal surgery. METHODS: A total of 294 elderly gynecological patients who were hospitalized in the affiliated Hospital of North Sichuan Medical College and underwent abdominal surgery from November 2019 to May 2022 were collected from the Union Digital Medical Record (UniDMR) Browser of the hospital. According to whether postoperative complications (infection, hypokalemia, hypoproteinemia, poor wound healing and intestinal obstruction) occurred, the patients were divided into complication group (n = 98) and non-complication group (n = 196). Univariate and multivariate logistic regression analysis were used to analyze the risk factors of complications in elderly gynecological patients undergoing abdominal surgery. The receiver operating characteristic (ROC) curve was used to determine the predictive value of the frailty index score in elderly gynecological patients with postoperative complications after abdominal surgery. RESULTS: Postoperative complications occurred in 98 of 294 elderly gynecological patients undergoing abdominal surgery, accounting for 33.3%, 5-mFI (OR1.63, 95%CI 1.07-2.46,P = 0.022), age (OR1.08,95%CI 1.02-1.15, P = 0.009), operation time (OR 1.01, 95%CI 1.00-1.01). P < 0.001) were independent risk factors for postoperative complications in elderly patients undergoing abdominal surgery, and the area under the curve of postoperative complications in elderly gynecological patients was 0.60. (95%CI: 0.53-0.67, P = 0.005) CONCLUSION: Five modified frailty index can effectively predict the occurrence of postoperative complications in elderly gynecological patients.

Aquaporins and Neuropathic Pain.

Neuropathic pain is a chronic secondary pain condition resulting from lesions or diseases of the peripheral or central nervous system (CNS). Neuropathic pain is closely related to edema, inflammation, increased neuronal excitability, and central sensitization caused by glutamate accumulation. Aquaporins (AQPs), mainly responsible for the transport and clearance of water and solute, play important roles in developing CNS diseases, especially neuropathic pain. This review focuses on the interaction of AQPs with neuropathic pain, and the potential of AQPs, especially aquaporins 4, as therapeutic targets.

A Randomized Controlled Trial: Examining the Impact of the Novel Double Setup Endotracheal Tube on the Success Rates of Awake Fiber-Optic Orotracheal Intubation.

BACKGROUND: Advancing the endotracheal tube (ETT) over a flexible bronchoscope (FB) during awake fiber-optic intubation (AFOI) is often impeded. Various maneuvers and tracheal tubes designed to overcome this obstruction may also be unsuccessful or costly. OBJECTIVE: The current study aimed to assess how the novel double configuration ETT affected AFOI success rates on the first attempt. METHODS: A randomized controlled experiment including 40 individuals receiving awake fiber-optic orotracheal intubation was performed in a 1:1 ratio with a single ETT railroaded with its bevel posteriorly (ST) or railroading with a double setup ETT (DT) over a flexible videoscope (FVS) for tracheal intubation. The number of intubation attempts, time spent intubating, and adverse events were examined and compared between the two groups. RESULTS: Twenty patients received a single ETT railroaded with the bevel posteriorly, and 20 patients received railroading with the double setup ETT during AFOI. Intubation on the first attempt was significantly greater in the DT group (90%) than in the ST group (35%). The intubation time was considerably shorter for the DT group (12.8 [7.8-16.9] s) when compared with the ST group (27.9 [16.3-91.0] s). Five patients were intubated by the alternative technique after failure to intubate for several attempts, and 3 cases were found to have a crease in the FVS after intubation in group ST. During topical anesthetic, three individuals in each group experienced transient oxygen desaturation. CONCLUSIONS: Our study discovered that the novel double setup tube could significantly improve the intubation success rate on the first attempt during AFOI for patients with challenging airway when a strategy based on a reduced gap between ETT and FB could not be applied.

Restoration of aquaporin-4 polarization in the spinal glymphatic system by metformin in rats with painful diabetic neuropathy.

Painful diabetic neuropathy (PDN) is a common complication in patients with diabetes, and its underlying mechanism remains unclear. Aquaporin-4 (AQP4) plays a crucial role in removing metabolic waste in the glymphatic system. In this study, we aimed to explore the relationship between the spinal glymphatic system and the effect of metformin on PDN. Male Sprague-Dawley rats were randomly allocated into the control group ( n = 10), the PDN group ( n = 10), and the metformin group ( n = 10). A high-fat and high-glucose diet combined with low-dose streptozotocin was used to induce PDN rats. We detected the clearance rate of the contrast agent in the spinal cord of each rat by MRI to reflect the function of the glymphatic system. Immunofluorescence was used to detect the localization of perivascular AQP4 in astrocyte endfeet. Furthermore, we measured the expression of AQP4 in the spinal cord by Western blot. Compared with the rats in the control group, PDN rats exhibited enhanced mechanical allodynia, decreased clearance rate of the contrast agent in the spinal glymphatic system, reversed AQP4 polarization, and increased expression of AQP4. After being treated with metformin, the rats showed opposite changes in the above characteristics. The analgesic effect of metformin on PDN may be related to its ability to restore spinal AQP4 polarization, thus promoting the function of the spinal glymphatic system.

Omicron variants escape the persistent SARS-CoV-2-specific antibody response in 2-year COVID-19 convalescents regardless of vaccination.

With the ongoing COVID-19 pandemic and the emergence of various SARS-CoV-2 variants, a comprehensive evaluation of long-term efficacy of antibody response in convalescent individuals is urgently needed. Several longitudinal studies had reported the antibody dynamics after SARS-CoV-2 acute infection, but the follow-up was mostly limited to 1 year or 18 months at the maximum. In this study, we investigated the durability, potency, and susceptibility to immune evasion of SARS-CoV-2-specific antibody in COVID-19 convalescents for 2 years after discharge. These results showed the persistent antibody-dependent immunity could protect against the WT and Delta variant to some extent. However, the Omicron variants (BA.1, BA.2, and BA.4/5) largely escaped this preexisting immunity in recovered individuals. Furthermore, we revealed that inactivated vaccines (BBIBP-CorV, CoronaVac, or KCONVAC) could improve the plasma neutralization and help to maintain the broadly neutralizing antibodies at a certain level. Notably, with the time-dependent decline of antibody, 1-dose or 2-dose vaccination strategy seemed not to be enough to provide immune protection against the emerging variants. Overall, these results facilitated our understanding of SARS-CoV-2-induced antibody memory, contributing to the development of immunization strategy against SARS-CoV-2 variants for such a large number of COVID-19 survivors.

Early monitoring-to-warning Internet of Things system for emerging infectious diseases via networking of light-triggered point-of-care testing devices.

Early monitoring and warning arrangements are effective ways to distinguish infectious agents and control the spread of epidemic diseases. Current testing technologies, which cannot achieve rapid detection in the field, have a risk of slowing down the response time to the disease. In addition, there is still no epidemic surveillance system, implementing prevention and control measures is slow and inefficient. Motivated by these clinical needs, a sample-to-answer genetic diagnosis platform based on light-controlled capillary modified with a photocleavable linker is first developed, which could perform nucleic acid separation and release by light irradiation in less than 30 seconds. Then, on site polymerase chain reaction was performed in a handheld closed-loop convective system. Test reports are available within 20 min. Because this method is portable, rapid, and easy to operate, it has great potential for point-of-care testing. Additionally, through multiple device networking, a real-time artificial intelligence monitoring system for pathogens was developed on a cloud server. Through data reception, analysis, and visualization, the system can send early warning signals for disease control and prevention. Thus, anti-epidemic measures can be implemented effectively, and deploying and running this system can improve the capabilities for the prevention and control of infectious diseases.

ß-Hydroxybutyrate Attenuates Painful Diabetic Neuropathy via Restoration of the Aquaporin-4 Polarity in the Spinal Glymphatic System.

Waste removal is essential for maintaining homeostasis and the normal function of the central nervous system (CNS). The glymphatic system based on aquaporin-4 (AQP4) water channels on the endfeet of astrocytes is recently discovered as the excretion pathway for metabolic waste products of CNS. In the CNS, α-syntrophin (SNTA1) directly or indirectly anchors AQP4 in astrocyte membranes facing blood vessels. Studies have indicated that ß-hydroxybutyrate (BHB) can raise the expression of SNTA1 and thus restoring AQP4 polarity in mice models with Alzheimer's disease. The study aims to evaluate the neuroprotective mechanism of BHB in rats with painful diabetic neuropathy (PDN). PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. Magnetic resonance imaging (MRI) was applied to observe the clearance of contrast to indicate the functional variability of the spinal glymphatic system. Mechanical allodynia was assessed by paw withdrawal threshold. The expressions of SNTA1 and AQP4 were tested, and the polarity reversal of AQP4 protein was measured. As demonstrated, PDN rats were manifested with deceased contrast clearance of the spinal glymphatic system, enhanced mechanical allodynia, lower expression of SNTA1, higher expression of AQP4, and reversed polarity of AQP4 protein. An opposite change in the above characteristics was observed in rats being treated with BHB. This is the first study that demonstrated the neuroprotective mechanism of BHB to attenuate PDN via restoration of the AQP4 polarity in the spinal glymphatic system and provides a promising therapeutic strategy for PDN.

Detection of SARS-CoV-2 Specific Antibodies in Saliva Samples.

Molecular assays on nasopharyngeal swabs act as a confirmatory test in coronavirus disease (COVID-19) diagnosis. However, the technical requirements of nasopharyngeal sampling and molecular assays limit the testing capabilities. Recent studies suggest the use of saliva for the COVID-19 diagnostic test. In this study, 44 patients diagnosed with COVID-19 in The Third People's Hospital of Shenzhen were enrolled. Saliva and serum specimens were obtained at different time points and the immunoglobulins against SARS-CoV-2 were measured. The results showed that saliva IgA presented a higher COI value than IgG and IgM. In matched saliva and serum samples, all saliva samples presented lower IgG levels than serum samples, and only one saliva sample presented a higher IgM level. The conversion rates of saliva IgA and the detection of viral nucleic acids were analyzed in the first and second weeks after hospitalization. The positive rates increased when combining saliva IgA and viral nucleic acid detection. In conclusion, our results provide evidence that saliva IgA could serve as a useful index for the early diagnosis of COVID-19.

Plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy induced by type 2 diabetes mellitus.

The glymphatic system is a recently discovered glial-dependent macroscopic interstitial waste clearance system that promotes the efficient elimination of soluble proteins and metabolites from the central nervous system. Its anatomic foundation is the astrocytes and aquaporin-4 (AQP4) water channels on the endfeet of astrocytes. The aim of this study is to evaluate the plasticity of the spinal glymphatic system in male SD rats with painful diabetic neuropathy (PDN) induced by type 2 diabetes mellitus. PDN rats were modeled under a high-fat and high-glucose diet with a low dose of streptozotocin. MRI was applied to observe the infiltration and clearance of contrast to indicate the functional variability of the glymphatic system at the spinal cord level. The paw withdrawal threshold was used to represent mechanical allodynia. The numerical change of glial fibrillary acidic protein (GFAP) positive astrocytes was assessed and the polarity reversal of AQP4 protein was measured by immunofluorescence. As a result, deceased contrast infiltration and clearance, enhanced mechanical allodynia, increased number of GFAP positive astrocytes, and reversed polarity of AQP4 protein were found in the PDN rats. The above molecular level changes may contribute to the impairment of the spinal glymphatic system in PDN rats. This study revealed the molecular and functional variations of the spinal glymphatic system in PDN rats and for the first time indicated that there might be a correlation between the impaired spinal glymphatic system and PDN rats.

Effects of dynamic individualized PEEP guided by driving pressure in laparoscopic surgery on postoperative atelectasis in elderly patients: a prospective randomized controlled trial.

BACKGROUND: Driving pressure (ΔP = Plateau pressure-PEEP) is highly correlated with postoperative pulmonary complications (PPCs) and appears to be a promising indicator for optimizing ventilator settings. We hypothesized that dynamic, individualized positive end-expiratory pressure (PEEP) guided by ΔP could reduce postoperative atelectasis and improve intraoperative oxygenation, respiratory mechanics, and reduce the incidence of PPCs on elderly patients undergoing laparoscopic surgery. METHODS: Fifty-one elderly patients who were subject to laparoscopic surgery participated in this randomized trial. In the PEEP titration group (DV group), the PEEP titration was decremented to the lowest ΔP and repeated every 1 h. Additional procedures were also performed when performing predefined events that may be associated with lung collapse. In the constant PEEP group (PV group), a PEEP of 6 cmH2O was used throughout the surgery. Moreover, zero PEEP was applied during the entire procedure in the conventional ventilation group (CV group). The primary objective of this study was lung ultrasound score noted at the end of surgery and 15 min after admission to the post-anesthesia care unit (PACU) at 12 lung areas bilaterally. The secondary endpoints were perioperative oxygenation function, expiratory mechanics, and the incidence of the PPCs. RESULTS: The lung ultrasound scores of the DV group were significantly lower than those in the PV group and CV group (P < 0.05), whereas there was no significant difference between the PV group and CV group (P > 0.05). The lung static compliance (Cstat) and ΔP at all the intraoperative time points in the DV group were significantly better compared to the PV group and the CV group (p < 0.05). CONCLUSIONS: Intraoperative titrated PEEP reduced postoperative lung atelectasis and improved respiratory mechanics in elderly patients undergoing laparoscopic surgery. Meanwhile, standard PEEP strategy is not superior to conventional ventilation in reducing postoperative pulmonary atelectasis in laparoscopic surgery.

Suppressive Monocytes Impair MAIT Cells Response via IL-10 in Patients with Severe COVID-19.

Immune cell responses are strikingly altered in patients with severe coronavirus disease 2019 (COVID-19), but the immunoregulatory process in these individuals is not fully understood. In this study, 23 patients with mild and 22 patients with severe COVID-19 and 6 asymptomatic carriers of COVID-19 were enrolled, along with 44 healthy controls (HC). Peripheral immune cells in HC and patients with COVID-19 were comprehensively profiled using mass cytometry. We found that in patients with severe COVID-19, the number of HLA-DRlow/- monocytes was significantly increased, but that of mucosal-associated invariant T (MAIT) cells was greatly reduced. MAIT cells were highly activated but functionally impaired in response to Escherichia coli and IL-12/IL-18 stimulation in patients with severe COVID-19, especially those with microbial coinfection. Single-cell transcriptome analysis revealed that IFN-stimulated genes were significantly upregulated in peripheral MAIT cells and monocytes from patients with severe COVID-19. IFN-α pretreatment suppressed MAIT cells' response to E. coli by triggering high levels of IL-10 production by HLA-DRlow/--suppressive monocytes. Blocking IFN-α or IL-10 receptors rescued MAIT cell function in patients with severe COVID-19. Moreover, plasma from patients with severe COVID-19 inhibited HLA-DR expression by monocytes through IL-10. These data indicate a unique pattern of immune dysregulation in severe COVID-19, which is characterized by enrichment of suppressive HLA-DRlow/- monocytes associated with functional impairment of MAIT cells through the IFN/IL-10 pathway.

Simulation-based training following a theoretical lecture enhances the performance of medical students in the interpretation and short-term retention of 20 cross-sectional transesophageal echocardiographic views: a prospective, randomized, controlled trial.

BACKGROUND: Both simulation-based training and video-based training serve as educational adjuncts for learning TEE among medical students. In the present study, we hypothesized that simulation-based training would better enhance the performance of medical students in the interpretation of 20 cross-sectional views compared to video-based training. METHODS: A total of 120 4th-year undergraduate medical students were enrolled in the present study. The study began with a pre-test of all the participants, followed by a 90-min theoretical lecture and a post-test. Subsequently, the participants were randomly divided into the video-based group (Group V) and simulation-based group (Group S). Next, Group V received 60 min of TEE video learning, while Group S received 60 min of TEE simulator training. After the respective training, both the groups undertook the retention-test 1 and retention-test 2, 1 week and 1 month later, respectively. The performance for each test was evaluated by five views, which were selected randomly and, respectively, from a set of 20 cross-sectional views. The primary outcome was the performance of the retention-test 1. Secondary outcomes included: (1) comparison the performances of the pre-test, post-test, and retention-test 2 between two groups; (2) comparison the performances of pre-test and post-test in the same group; (3) comparison the performances of retention-test 1, and retention-test 2 in the same group. RESULTS: Better performances were observed in Group S in both retention-test 1 (Group V: 63.2 [52.6, 77.6] vs. Group S: 89.5 [68.4, 100.0], P < 0.001) and retention-test 2 (Group V: 58.0 [48.0, 72.0] vs. Group S: 74.0 [64.0, 80.0], P < 0.001) compared to Group V. No statistically significant differences were observed in the performances of pre-test (Group V: 8.3 [4.2, 12.5] vs. Group S: 8.3 [4.2, 12.5], P = 0.825) or post-test (Group V: 46.2 [38.5, 57.7] vs. Group S: 44.2 [38.5, 56.7], P = 0.694) between the two groups. The improvement had been observed in the post-test, compared with pre-test in the same group, respectively (Group V in post-test: 46.2 [38.5, 57.7] vs. Group V in pre-test: 8.3 [4.2, 12.5], P < 0.001; Group S in post-test: 44.2 [38.5, 56.7] vs. Group S in pre-test: 8.3 [4.2, 12.5], P < 0.001). However, the performance in retention-test 2 was significantly reduced, compared with retention-test 1 in the same group, respectively (Group V in retention-test 2: 58.0 [48.0, 72.0] vs. Group V in retention-test 1: 63.2 [52.6, 77.6] P = 0.005; Group S in retention-test 2: 74.0 [64.0, 80.0] vs. Group S in retention-test 1: 89.5 [68.4, 100.0], P < 0.001). CONCLUSIONS: Following a 90-min theoretical lecture, simulation-based training better enhanced the performance of medical students in the interpretation and short-term retention of 20 cross-sectional views compared to video-based training. TRIAL REGISTRATION: http://www.chictr.org.cn ( ChiCTR2000033519 , 3/June/2020).

Effect of low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy: a prospective randomized trial.

BACKROUND: At present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery - 15 (QoR-15) questionnaire. METHODS: One hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded. RESULTS: Compared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery. CONCLUSIONS: Low-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively. TRIAL REGISTRATION: ChiCTR1900024731 . Date of registration: 25/07/2019.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy.

Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors. As effective carriers, metal-organic frameworks (MOFs) have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity. Herein, we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF (MIL101-NH2) as the core carrier; the MOF was dual-dressed with photoacoustic and fluorescent signal donors (indocyanine green, ICG) and immune adjuvants (cytosine-phosphate-guanine sequence, CpG) and named ICG-CpG@MOF. This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging (fluorescence, photoacoustic, photothermal and magnetic resonance imaging) of the tumor. Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation. ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment. Furthermore, the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system, which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects. This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.