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Objectives: To evaluate the effectiveness of computer-aided design (CAD)/computer-aided manufacturing (CAM) in designing and manufacturing 3D-printed dental models used to make thermoplastic removable splints for children with traumatized anterior permanent teeth., Methods: A total of 28 patients with dental trauma (subluxation, extrusive luxation, and lateral luxation) were divided into experimental (14 patients) and control groups (14 patients). The experimental group was treated with the removable splint made using a new 3D printed dental model designed with CAD/CAM technology, while the control group received a wire-composite splint. Follow-up was performed at week 2 and 1, 2, 3, 6, 12, 18, and 24 months post-treatment, and every year after that. The traumatized teeth were evaluated according to clinical symptoms, tooth color, mobility, position, percussion pain, abnormal percussion sounds indicating ankylosis or other pathosis, swelling, fistula of gums, vitality test, and radiographic examination., Results: No significant difference was found in gender and age between the two groups. The experimental group had 23 traumatic teeth, and the control group had 24 traumatic teeth. Traumatic teeth in the two groups most commonly involved open apex teeth (>90 %). The average follow-up time for the experimental and control group was 35.47±14.23 and 32.92±14.79 months (P > 0.05), respectively. The pulp survival rate and periodontal healing rate in the experimental group (86.96 %, 91.30 %) were higher compared to the control group (62.50 %, 75.00 %) (all P > 0.05)., Conclusion: A removable splint made by a 3D printed dental model designed with CAD/CAM technology achieved an equivalent treatment effect to a wire-composite splint., Clinical Significance: A 3D-printed dental model designed with CAD/CAM technology can be used to fabricate removable splints, which in turn can decrease iatrogenic injuries frequently encountered during the traditional model production process. For example, taking the impression directly from the patient's mouth can cause displacement of a traumatized tooth or even exfoliation. The removable splints produced using a new 3D-printed dental model can meet clinical treatment requirements of traumatized teeth, especially for children and adolescents with occlusal trauma in mixed dentition., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Loss of chromosome 9p is an important biomarker in the malignant transformation of oral leukoplakia (OLK) to head and neck squamous cell carcinoma (HNSCC), and is associated with the prognosis of HNSCC patients. However, various challenges have prevented 9p loss from being assessed in clinical practice. The objective of this study was to develop a pathomics-based artificial intelligence (AI) model for the rapid and cost-effective prediction of 9p loss (9PLP)., Materials and Methods: 333 OLK cases were retrospectively collected with hematoxylin and eosin (H&E)-stained whole slide images and genomic alteration data from multicenter cohorts to develop the genomic alteration prediction AI model. They were divided into a training dataset (n=217), a validation dataset (n=93), and an external testing dataset (n=23). The latest Transformer method and XGBoost algorithm were combined to develop the 9PLP model. The AI model was further applied and validated in two multicenter HNSCC datasets (n=42, n=365, respectively). Moreover, the combination of 9PLP with clinicopathological parameters was used to develop a nomogram model for assessing HNSCC patient prognosis., Results: 9PLP could predict chromosome 9p loss rapidly and effectively using both OLK and HNSCC images, with the area under the curve achieving 0.890 and 0.825, respectively. Furthermore, the predictive model showed high accuracy in HNSCC patient prognosis assessment (the area under the curve was 0.739 for 1-year prediction, 0.705 for 3-year prediction, and 0.691 for 5-year prediction)., Conclusion: To the best of our knowledge, this study developed the first genomic alteration prediction deep learning model in OLK and HNSCC. This novel AI model could predict 9p loss and assess patient prognosis by identifying pathomics features in H&E-stained images with good performance. In the future, the 9PLP model may potentially contribute to better clinical management of OLK and HNSCC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: We aim to develop a YOLOX-based convolutional neural network model for the precise detection of multiple oral lesions, including OLP, OLK, and OSCC, in patient photos., Materials and Methods: We collected 1419 photos for model development and evaluation, conducting both a comparative analysis to gauge the model's capabilities and a multicenter evaluation to assess its diagnostic aid, where 24 participants from 14 centers across the nation were invited. We further integrated this model into a mobile application for rapid and accurate diagnostics., Results: In the comparative analysis, our model overperformed the senior group (comprising three most experienced experts with more than 10 years of experience) in macro-average recall (85 % vs 77.5 %), precision (87.02 % vs 80.29 %), and specificity (95 % vs 92.5 %). In the multicenter model-assisted diagnosis evaluation, the dental, general, and community hospital groups showed significant improvement when aided by the model, reaching a level comparable to the senior group, with all macro-average metrics closely aligning or even surpassing with those of the latter (recall of 78.67 %, 74.72 %, 83.54 % vs 77.5 %, precision of 80.56 %, 76.42 %, 85.15 % vs 80.29 %, specificity of 92.89 %, 91.57 %, 94.51 % vs 92.5 %)., Conclusion: Our model exhibited a high proficiency in detection of oral lesions, surpassing the performance of highly experienced specialists. The model can also help specialists and general dentists from dental and community hospitals in diagnosing oral lesions, reaching the level of highly experienced specialists. Moreover, our model's integration into a mobile application facilitated swift and precise diagnostic procedures., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: The superior thyroid artery perforator flap (STAPF) was previously presented as a type of locoregional pedicled flap for lateral facial and temple defects. In this study, we aimed to present our clinical experience with this flap for the reconstruction of soft tissue defects after oral cancer surgery., Methods: From February 2019 to December 2022, 24 patients with oral cancers at the School and Hospital of Stomatology, Peking University were included. Among these patients, 10 had cancers located in the tongue, five in the cheek inside the oral cavity, three in the lower gingiva, two in the upper gingiva, two in the floor of the mouth, and two in the palate. All patients were treated with extended tumor resection, neck dissection, and STAPFs to reconstruct the soft tissue defects. The details of the flap, including the flap size, venous flow, vascular pedicle length, the attatched muscle, and operation time were evaluated., Results: The dimensions of the flap skin paddle ranged from 3 cm × 5 cm to 6 × 14 cm. Fourteen patients had a closely concomitant superior thyroid vein perforator. Ten patients had non-closely concomitant superior thyroid veins perforators which retrograde external jugular vein. The vascular pedicle length ranged from 5 to 9 cm. The infrahyoid muscle group or sternocleidomastoid muscle was included in the flaps in three patients. A total of 23/24 flaps were successful., Conclusions: The STAPF is a viable reconstructive option for patients with oral cancers. It has the advantages of being robust, being thin, short operation time, and minor donor site complications., Level of Evidence: 4 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Intraductal papillary neoplasm of the bile duct (IPNB) is a heterogeneous disease similar to intraductal papillary mucinous neoplasm of the pancreas. These lesions have been recognized as one of the three major precancerous lesions in the biliary tract since 2010. In 2018, Japanese and Korean pathologists reached a consensus, classifying IPNBs into type l and type 2 IPNBs. IPNBs are more prevalent in male patients in East Asia and are closely related to diseases such as cholelithiasis and schistosomiasis. From a molecular genetic perspective, IPNBs exhibit early genetic variations, and different molecular pathways may be involved in the tumorigenesis of type 1 and type 2 IPNBs. The histological subtypes of IPNBs include gastric, intestinal, pancreaticobiliary, or oncocytic subtypes, but type 1 IPNBs typically exhibit more regular and well-organized histological features than type 2 IPNBs and are more commonly found in the intrahepatic bile ducts with abundant mucin. Due to the rarity of these lesions and the absence of specific clinical and laboratory features, imaging is crucial for the preoperative diagnosis of IPNB, with local bile duct dilation and growth along the bile ducts being the main imaging features. Surgical resection remains the optimal treatment for IPNBs, but negative bile duct margins and the removal of lymph nodes in the hepatic hilum significantly improve the postoperative survival rates for patients with IPNBs., (© 2024. Huazhong University of Science and Technology.)

Background: Schizophrenia is one of the leading causes of disability. Paliperidone palmitate once-monthly injection (PP1M) was developed to provide consistent drug delivery and improve medication adherence for maintenance treatment. It is well known that patients with schizophrenia have higher cardiovascular risks, however little is known about the cardiovascular risks of patients with schizophrenia treated with PP1M in Asia., Objective: This study aimed to estimate the incidence of cardiovascular events after initiating PP1M treatment and evaluate the cardiovascular risk associations compared with oral second-generation antipsychotics (SGAs)., Methods: Data from Taiwan's National Health Insurance Research Database were used to identify a cohort of adult patients with schizophrenia who received any SGAs from 1 March 2012 to 31 December 2018. Patients who initiated PP1M treatment were enrolled for descriptive analysis of incidence rates. PP1M patients were propensity matched 1:1 to patients initiating a new oral SGA, for comparative analysis based on demographics, clinical characteristics and treatment history at baseline, in three-step matching procedures, following the prevalent new-user design to enhance comparability. Follow-up ended at the end of the treatment episode of index drug, death, last record available, or end of the study (31 December 2019). Study endpoints included serious cardiovascular events (including severe ventricular arrhythmia and sudden death), expanded serious cardiovascular events (which further included acute myocardial infarction and ischemic stroke), and cardiovascular hospitalizations. Risks of study endpoints between matched cohorts were compared using Cox regression., Results: Overall, 11,023 patients initiating PP1M treatment were identified (49.5% were females; mean age of 43.2 [12.2] years). Overall incidences for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 3.92, 7.88 and 51.96 per 1000 person-years, respectively. In matched cohort analysis (N = 10,115), the hazard ratios (HRs) between initiating PP1M and a new oral SGA for serious cardiovascular events, expanded serious cardiovascular events, and cardiovascular hospitalizations were 0.86 (95% confidence interval [CI] 0.55-1.36), 0.88 (95% CI 0.63-1.21), and 0.78 (95% CI 0.69-0.89), respectively., Conclusion: This study reported the population-based incidence of cardiovascular events in schizophrenic patients initiating PP1M treatment. PP1M was not associated with increased risks of serious cardiovascular events but was potentially associated with lower risks of cardiovascular hospitalizations compared with oral SGAs., (© 2024. The Author(s).)

Background: In practice, the collected datasets for data analysis are usually incomplete as some data contain missing attribute values. Many related works focus on constructing specific models to produce estimations to replace the missing values, to make the original incomplete datasets become complete. Another type of solution is to directly handle the incomplete datasets without missing value imputation, with decision trees being the major technique for this purpose., Objective: To introduce a novel approach, namely Deep Learning-based Decision Tree Ensembles (DLDTE), which borrows the bounding box and sliding window strategies used in deep learning techniques to divide an incomplete dataset into a number of subsets and learning from each subset by a decision tree, resulting in decision tree ensembles., Method: Two medical domain problem datasets contain several hundred feature dimensions with the missing rates of 10% to 50% are used for performance comparison., Results: The proposed DLDTE provides the highest rate of classification accuracy when compared with the baseline decision tree method, as well as two missing value imputation methods (mean and k-nearest neighbor), and the case deletion method., Conclusion: The results demonstrate the effectiveness of DLDTE for handling incomplete medical datasets with different missing rates.

Data discretization aims to transform a set of continuous features into discrete features, thus simplifying the representation of information and making it easier to understand, use, and explain. In practice, users can take advantage of the discretization process to improve knowledge discovery and data analysis on medical domain problem datasets containing continuous features. However, certain feature values were frequently missing. Many data-mining algorithms cannot handle incomplete datasets. In this study, we considered the use of both discretization and missing-value imputation to process incomplete medical datasets, examining how the order of discretization and missing-value imputation combined influenced performance. The experimental results were obtained using seven different medical domain problem datasets: two discretizers, including the minimum description length principle (MDLP) and ChiMerge; three imputation methods, including the mean/mode, classification and regression tree (CART), and k-nearest neighbor (KNN) methods; and two classifiers, including support vector machines (SVM) and the C4.5 decision tree. The results show that a better performance can be obtained by first performing discretization followed by imputation, rather than vice versa. Furthermore, the highest classification accuracy rate was achieved by combining ChiMerge and KNN with SVM., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Background: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear., Methods: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias., Results: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively., Conclusions: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy., (© 2022. Society of Surgical Oncology.)

Supermicrosurgery involves the dissection and anastomosis of vessels<0.8 mm in diameter with minimal donor site morbidity. This study evaluated the feasibility and outcomes of free flaps using supermicrosurgery to repair oncological defects in the maxillofacial region. Forty-two patients were treated with supermicrosurgery to repair oncological defects in the maxillofacial region between December 2015 and February 2021. The supermicrosurgery technique was used for different types of free flap, including 24 superficial circumflex iliac artery perforator flaps, seven anterolateral thigh flaps, three peroneal artery perforator flaps, five medial femoral condyle osteo-adipofascial flaps, and three profunda artery perforator flaps. An artery-to-artery approach was used in 38 patients; venous grafts for anastomosis were used in four patients to resolve an arterial discrepancy. Forty-one flaps (97.6%) survived. Thirty-six patients (85.7%) healed without any complications; three flaps required revision surgery including one lost, one demonstrated wound dehiscence, and two demonstrated wound infection. Supermicrosurgery is a useful complement to conventional microsurgery in head and neck reconstruction., (Copyright © 2022 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Anorexia nervosa (AN) is a serious and potentially life-threatening eating disorder characterized by starvation and malnutrition, a high prevalence of coexisting psychiatric conditions, marked treatment resistance, frequent medical complications, and a substantial risk of death. Body mass index (BMI) is a key measure of treatment outcome of AN and it is necessary to evaluate the long-term prognosis of AN. This study aimed to better assess the BMI course trend between different medications and timepoints in order to improve AN treatment in clinical practice., Methods: During the period 2010-2021, we retrospectively reviewed historical data of all patients diagnosed with AN. There were two groups in this study, which were based on the duration of follow-up. Group A was a 6-month follow-up group, comprising 93 patients (mean age 19.6 ± 6.8 years), with BMI assessed at three consecutive time points: first outpatient visit (T0), three months follow-up (T3), and six months follow-up (T6). Group B was a 12-month follow-up group comprising 36 patients (mean age 17.0 ± 5.2 years) with BMI assessed at five consecutive time points: first outpatient visit (T0), three months follow-up (T3), six months follow-up (T6), nine months follow-up (T9), and twelve months follow-up (T12). In our study, we retrospectively compared BMI courses based on patients' usage of medication using the following variables: single medication, switching medications, combined medications, and without medications. The primary outcome measurement was BMI recorded at the 6-month follow-up and the 12-month follow-up respectively. In our study, which was conducted at Taichung Veterans General Hospital, we reviewed outpatient medical records of all patients with AN who were seen at the hospital during the period 2010-2021., Results: In Group A (6-month follow-up), patients treated with antidepressants showed a mean BMI increase of 1.3 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 1.1 (p = 0.01); patients treated with switching medications showed a mean BMI increase of 0.1 (p = 0.397); patients treated with combined medications showed a mean BMI increase of 0.5 (p = 0.208); and patients treated without medications showed a mean BMI increase of 0.1 (p = 0.821). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants and antipsychotics in the 6-month follow-up group. In Group B (12-month follow-up), patients treated with antidepressants showed a mean BMI increase of 2.7 (p < 0.001); patients treated with antipsychotics showed a mean BMI increase of 2.8 (p = 0.168); patients treated with switching medications showed a mean BMI decrease of 0.8 (p = 0.595); patients treated with combined medications showed a mean BMI increase of 1.6 (p = 0.368); and patients treated without medications showed a mean BMI increase of 1.0 (p = 0.262). The results indicated that patients with AN had a significant BMI increase after treatment with antidepressants at the 12-month follow-up., Conclusions: AN is a complex disease caused by multiple factors. Evaluating its long-term prognosis is crucial. Our study provides insights and highlights three key findings: 1) medication adherence is crucial in treating AN, 2) frequent switching of medications may not promote weight gain and may also require a re-establishment of rapport with patients with AN, and 3) pharmacotherapy, especially antidepressants, is more effective than no treatment. Further research is needed to confirm these findings., (© 2023. The Author(s).)

Objective: T cells are critical in the pathogenesis of systemic lupus erythematosus (SLE) in that they secrete inflammatory cytokines, help autoantibody production, and form autoreactive memory T cells. Although the contribution of T cells to several forms of organ-mediated damage in SLE has been previously demonstrated, the role of T cells in neuropsychiatric SLE (NPSLE), which involves diffuse central nervous system manifestations and is observed in 20-40% of SLE patients, is not known. Therefore, we conducted this study to evaluate how behavioral deficits are altered after depletion or transfer of T cells, to directly assess the role of T cells in NPSLE., Methods: MRL/lpr mice, an NPSLE mouse model, were either systemically depleted of CD4+ T cells or intracerebroventricularly injected with choroid plexus (CP)-infiltrating T cells and subsequently evaluated for alterations in neuropsychiatric manifestations. Our study end points included evaluation of systemic disease and assessment of central nervous system changes., Results: Systemic depletion of CD4+ T cells ameliorated systemic disease and cognitive deficits. Intracerebroventricular injection of CP-infiltrating T cells exacerbated depressive-like behavior and worsened cognition in recipient mice compared with mice who received injection of splenic lupus T cells or phosphate buffered saline. Moreover, we observed enhanced activation in CP-infiltrating T cells when cocultured with brain lysate-pulsed dendritic cells in comparison to the activation levels observed in cocultures with splenic T cells., Conclusion: T cells, and more specifically CP-infiltrating antigen-specific T cells, contributed to the pathogenesis of NPSLE in mice, indicating that, in the development of more targeted treatments for NPSLE, modulation of T cells may represent a potential therapeutic strategy., (© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.)

Objective: Endometrial cancer is the most common malignancy of the female genital tract worldwide, and the associated relationship between endometrial cancer formation and various antipsychotics need to be confirmed., Methods: We conducted a case-control study by using data from Taiwan National Health Insurance Research Database to compare individual antipsychotic exposure between females with and without endometrial cancer. Among 14,079,089 females in the 12-year population-based national dataset, 9,502 females with endometrial cancer were identified. Their medical records of exposure to antipsychotics, including quetiapine, haloperidol, risperidone, olanzapine, amisulpride, clozapine, and aripiprazole, for up to 3 years before endometrial cancer diagnosis were reviewed. Daily dosage and cumulative exposure days were analyzed in the risky antipsychotic users. Additionally, the subsequent 5-year mortality rate of endometrial cancer among users of the risky antipsychotic were also analyzed., Results: Among endometrial cancer patients, the proportion of those who have used haloperidol before being diagnosed with endometrial cancer is significantly higher than other antipsychotic users. The significant odds ratio (OR) and a 95% confidence interval of 1.75 (1.31-2.34) were noted. Furthermore, haloperidol users were associated with a significantly higher 5-year mortality rate after getting endometrial cancer than non-users., Conclusion: There is a high correlation between the use of haloperidol and endometrial cancer formation. However, the underlying pathological biomechanisms require additional investigations.

Beyond their pulmonary disease, many COVID-19 patients experience a complex constellation of characteristics, including hyperinflammatory responses, autoimmune disorders, and coagulopathies. However, the pathogenesis of these aspects of COVID-19 is obscure. More than 90% of people are latently infected with the lymphotropic herpesviruses Epstein-Barr Virus (EBV) and/or Human Herpesvirus-6 (HHV-6). Some of the inflammatory features of COVID-19 resemble clinical syndromes seen during EBV and HHV-6 infection, and these latent viruses can be reactivated by inflammatory mediators. We hypothesized that EBV and HHV-6 reactivation might be a common feature of early COVID-19, particularly in patients with more inflammation. We tested for EBV and HHV-6 reactivation in 67 patients acutely hospitalized with COVID-19 using previously validated quantitative PCR assays on the plasma. In our cohort, we found that 15/67 (22.4%) patients had detectable EBV and 3/67 (4.5%) had detectable HHV-6. This frequency of activation is somewhat more than the frequency reported for some healthy cohorts, such as blood donors and other healthy control cohorts. There was no association between EBV or HHV-6 and markers indicative of more inflammatory disease. We conclude that EBV and HHV-6 activation at about day 7 of hospitalization occurred in a modest fraction of our cohort of COVID-19 patients and was not associated with high levels of inflammation. In the modest fraction of patients, EBV and HHV-6 reactivation could contribute to some features of acute disease and pre-disposition to post-acute sequelae in a subset of patients.

Background: Whilst antipsychotics are the mainstay of treatment for schizophrenia spectrum disorders, there have been numerous attempts to identify biomarkers that can predict treatment response. One potential marker may be psychomotor abnormalities, including catatonic symptoms. Early studies suggested that catatonic symptoms predict poor treatment response, whilst anecdotal reports of rare adverse events have been invoked against antipsychotics. The efficacy and safety of antipsychotics in the treatment of this subtype of schizophrenia have rarely been studied in randomised controlled trials (RCTs)., Objectives: To compare the effects of any single antipsychotic medication with another antipsychotic or with other pharmacological agents, electroconvulsive therapy (ECT), other non-pharmacological neuromodulation therapies (e.g. transcranial magnetic stimulation), or placebo for treating positive, negative, and catatonic symptoms in people who have schizophrenia spectrum disorders with catatonic symptoms., Search Methods: We searched the Cochrane Schizophrenia Group's Study-Based Register of Trials, which is based on CENTRAL, MEDLINE, Embase, CINAHL, PsycINFO, PubMed, ClinicalTrials.gov, the ISRCTN registry, and WHO ICTRP, on 19 September 2021. There were no language, date, document type, or publication status limitations for inclusion of records in the register. We also manually searched reference lists from the included studies, and contacted study authors when relevant., Selection Criteria: All RCTs comparing any single antipsychotic medication with another antipsychotic or with other pharmacological agents, ECT, other non-pharmacological neuromodulation therapies, or placebo for people who have schizophrenia spectrum disorders with catatonic symptoms., Data Collection and Analysis: two review authors independently inspected citations, selected studies, extracted data, and appraised study quality. For binary outcomes, we planned to calculate risk ratios and their 95% confidence intervals (CI) on an intention-to-treat basis. For continuous outcomes, we planned to calculate mean differences between groups and their 95% CI. We assessed risk of bias for the included studies, and created a summary of findings table; however, we did not assess the certainty of the evidence using the GRADE approach because there was no quantitative evidence in the included study., Main Results: Out of 53 identified reports, one RCT including 14 hospitalised adults with schizophrenia and catatonic symptoms met the inclusion criteria of the review. The study, which was conducted in India and lasted only three weeks, compared risperidone with ECT in people who did not respond to an initial lorazepam trial.   There were no usable data reported on the primary efficacy outcomes of clinically important changes in positive, negative, or catatonic symptoms. Whilst both study groups improved in catatonia scores on the Bush-Francis Catatonia Rating Scale (BFCRS), the ECT group showed significantly greater improvement at week 3 endpoint (mean +/- estimated standard deviation; 0.68 +/- 4.58; N = 8) than the risperidone group (6.04 +/- 4.58; N = 6; P = 0.035 of a two-way analysis of variance (ANOVA) for repeated measures originally conducted in the trial). Similarly, both groups improved on the Positive and Negative Syndrome Scale (PANSS) scores by week 3, but ECT showed significantly greater improvement in positive symptoms scores compared with risperidone (P = 0.04). However, data on BFCRS scores in the ECT group appeared to be skewed, and mean PANSS scores were not reported, thereby precluding further analyses of both BFCRS and PANSS data according to the protocol.  Although no cases of neuroleptic malignant syndrome were reported, extrapyramidal symptoms as a primary safety outcome were reported in three cases in the risperidone group. Conversely, headache (N = 6), memory loss (N = 4), and a prolonged seizure were reported in people receiving ECT. These adverse effects, which were assessed as specific for antipsychotics and ECT, respectively, were the only adverse effects reported in the study. However, the exact number of participants with adverse events was not clearly reported in both groups, precluding further analysis.  Our results were based only on a single study with a very small sample size, short duration of treatment, unclear or high risk of bias due to unclear randomisation methods, possible imbalance in baseline characteristics, skewed data, and selective reporting. Data on outcomes of general functioning, global state, quality of life, and service use, as well as data on specific phenomenology and duration of catatonic symptoms, were not reported., Authors' Conclusions: We found only one small, short-term trial suggesting that risperidone may improve catatonic and positive symptoms scale scores amongst people with schizophrenia spectrum disorders and catatonic symptoms, but that ECT may result in greater improvement in the first three weeks of treatment. Due to small sample size, methodological shortcomings and brief duration of the study, as well as risk of bias, the evidence from this review is of very low quality. We are uncertain if these are true effects, limiting any conclusions that can be drawn from the evidence. No cases of neuroleptic malignant syndrome were reported, but we cannot rule out the risk of this or other rare adverse events in larger population samples.  High-quality trials continue to be necessary to differentiate treatments for people with symptoms of catatonia in schizophrenia spectrum disorders. The lack of consensus on the psychopathology of catatonia remains a barrier to defining treatments for people with schizophrenia. Better understanding of the efficacy and safety of antipsychotics may clarify treatment for this unique subtype of schizophrenia., (Copyright © 2022 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Wastewater based epidemiology (WBE) has emerged as a tool to track the spread of SARS-CoV-2. However, sampling at wastewater treatment plants (WWTPs) cannot identify transmission hotspots within a city. Here, we sought to understand the diurnal variations (24 h) in SARS-CoV-2 RNA titers at the neighborhood level, using pump stations that serve vulnerable communities (e.g., essential workers, more diverse communities). Hourly composite samples were collected from wastewater pump stations located in (i) a residential area and (ii) a shopping district. In the residential area, SARS-CoV-2 RNA concentration (N1, N2, and E assays) varied by up to 42-fold within a 24 h period. The highest viral load was observed between 5 and 7 am, when viral RNA was not diluted by stormwater. Normalizing peak concentrations during this time window with nutrient concentrations (N and P) enabled correcting for rainfall to connect sewage to clinical cases reported in the sewershed. Data from the shopping district pump station were inconsistent, probably due to the fluctuation of customers shopping at the mall. This work indicates pump stations serving the residential area offer a narrow time period of high signal intensity that could improve the sensitivity of WBE, and tracer compounds (N, P concentration) can be used to normalize SARS-CoV-2 signals during rainfall., Competing Interests: The authors declare no competing financial interest., (© 2022 American Chemical Society.)

Objective: To analyze the efficacy and prognostic factors in children with parameningeal rhabdomyosarcoma (PMRMS) treated by 125 I brachytherapy combined with chemotherapy. Methods: A retrospective analysis of the clinical data of 33 pediatric patients treated with 125 I brachytherapy combined with chemotherapy in Peking University Stomatological Hospital from July 2013 to October 2018 was carried out to analyze the efficacy and prognostic factors. Results: Among the 33 patients, 19 were males and 14 were females; the median age was 4 years old (1-12 years old). There were 17 cases with embryonic type, 9 cases with alveolar type, and 7 with undifferentiated type; 26 cases with original PMRMS, and 7 cases with recurrent PMRMS. The tumors occurred in subtemporal-mastoid area in 15 patients, while nasopalatine-paranasal area in 6 cases, and parapharyngeal-submandibular area in 12 cases. There were 28 patients in IRS Ⅲ, and 5 patients in IRS Ⅳ. As for the risk level, 28 cases were in the middle-risk group and 5 cases in the high-risk group. The median follow-up time was 52 months. The 1, 3, and 5-year local control rates were 87.9%, 58.6%, and 49.9%, and the 1, 3, and 5-year survival rates were 93.8%, 60.5%, and 47.5%, respectively. The 5-year local control rate and 5-year survival rate of 12 patients with the tumor in the parapharyngeal-submandibular area were 91.7% and 100%, respectively. The 5-year local control rate and 5-year survival rate of the 6 patients with tumor in the nasopalatine-paranasal area were both 83.3%. The 3-year local control rate and 3-year survival rate of the 15 patients with tumor in the subtemporal-mastoid area were 17.5% and 21.4%. The multivariate survival analysis using Cox proportional risk regression model showed that the tumor located in the subtemporal-mastoid area was an independent risk factor affecting the 5-year overall survival rate ( HR =38.40, 95% CI : 4.87-302.52, P =0.001). Within 3 months after 125 I seed implantation, the incidence of acute radiotherapy adverse reactions in all patients was 84.8% (28/33). Twenty-one patients (63.6%) had a grade 1 acute radiotherapy reaction, and 7 cases (21.2%) had a grade 2 acute radiotherapy reaction. No acute radiotherapy adverse reactions of grade 3 or 4 occurred. Three months after 125 I seed implantation, the adverse reactions were significantly alleviated, and no adverse reactions of grade 3 or above such as skin ulcer or salivary gland fibrosis occurred, and no serious cranio-maxillofacial deformities occurred. Conclusions: 125 I seed brachytherapy combined with chemotherapy has a definite clinical effect in the treatment of children with parameningeal rhabdomyosarcoma. The prognosis of rhabdomyosarcoma in the parapharyngeal-submandibular area and nasopalatine-paranasal area is better than that in the subtemporal-mastoid area.

Abnormal immune cell functions are commonly related to various diseases, including cancer, autoimmune diseases, and infectious diseases. Messenger RNA (mRNA)-based therapy can regulate the functions of immune cells or assign new functions to immune cells, thereby generating therapeutic immune responses to treat these diseases. However, mRNA is unstable in physiological environments and can hardly enter the cytoplasm of target cells; thus, effective mRNA delivery systems are critical for developing mRNA therapy. The two mRNA vaccines of Pfizer-BioNTech and Moderna have demonstrated that lipid nanoparticles (LNPs) can deliver mRNA into dendritic cells (DCs) to induce immunization against severe acute respiratory syndrome coronavirus 2, which opened the floodgates to the development of mRNA therapy. Apart from DCs, other immune cells are promising targets for mRNA therapy. This review summarized the barriers to mRNA delivery and advances in mRNA delivery for regulating the functions of different immune cells., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: This study was performed to examine changes in the number of patient visits and types of oral services in an oral emergency department from the beginning to the control stage of the coronavirus disease 2019 (COVID-19) outbreak in Beijing., Methods: The numbers of daily oral emergency visits from January 20 to March 24, 2020, at a dental university hospital in Beijing and daily newly confirmed COVID-19 cases in Beijing during the same period were collected and analysed. All oral emergency patient information (including sex, age, and oral diagnosis) was also collected and analysed. Patients with incomplete medical data were excluded., Results: In total, 12,416 patients were included in this study. The number of daily emergency visits was negatively correlated with the number of newly confirmed local COVID-19 cases in Beijing (P < .001). The number of daily emergency visits during the COVID-19 stable period in Beijing was greater than that during the outbreak period (P < .001). Compared to those in the COVID-19 outbreak period, the percentages of females, children and adolescents, patients with acute toothache, and patients with nonurgent cases were higher in the stable period, and the numbers of patients with toothache, trauma, infection, and nonemergency conditions increased in the COVID-19 stable period (P < .001)., Conclusions: COVID-19 significantly influenced the number of patient visits and the percentages of patients with oral emergency situations in the oral emergency department. There were obvious differences in treatment seeking for oral emergencies between the COVID-19 periods in Beijing. There was an inverse relationship between daily oral emergency visits and daily confirmed COVID-19 cases in Beijing., Competing Interests: Conflict of interest None disclosed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: To determine the neck management of tongue cancer, this study attempted to construct an artificial neural network (ANN)-assisted model based on computed tomography (CT) radiomics of primary tumors to predict neck lymph node (LN) status in patients with tongue squamous cell carcinoma (SCC)., Materials and Methods: Three hundred thirteen patients with tongue SCC were retrospectively included and randomly divided into training (60%), validation (20%) and internally independent test (20%) sets. In total, 1673 feature values were extracted after the semiautomatic segmentation of primary tumors and set as input layers of a classical 3-layer ANN incorporated with or without clinical LN (cN) status after dimension reduction. The receiver operating characteristic (ROC) curve, accuracy (ACC), sensitivity (SEN), specificity (SPE), area under curve (AUC) and Net Reclassification Index (NRI), were used to evaluate and compare the models., Results: Four models with different settings were constructed. The ACC, SEN, SPE and AUC reached 84.1%, 93.1%, 76.5% and 0.943 (95% confidence interval: 0.891-0.996, p<.001), respectively, in the test set. The NRI of models compared with radiologists reached 40% (p<.001). The occult nodal metastasis rate was reduced from 30.9% to a minimum of 12.7% in the T1-2 group., Conclusion: ANN-based models that incorporated CT radiomics of primary tumors with traditional LN evaluation were constructed and validated to more precisely predict neck LN metastasis in patients with tongue SCC than with naked eyes, especially in early-stage cancer., Competing Interests: Declarations of interest We have no Conflict of Interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

The deep circumflex iliac artery perforator flap with iliac crest (DCIAPF) is considered a favourable single-flap option for oromandibular reconstruction. The aim of this study was to evaluate the effectiveness of venous superdrainage using the superficial circumflex iliac vein (SCIV) in the DCIAPF for oromandibular reconstruction. The data of 22 patients (12 female, 10 male) aged 10-76 years (median 53 years) who underwent simultaneous oromandibular reconstruction with a DCIAPF were reviewed retrospectively. Eleven patients received the DCIAPF with SCIV for superdrainage (group A) and another 11 patients received the conventional single-pedicled DCIAPF flap (group B). No flap loss occurred in either group. Venous congestion due to relative venous insufficiency was significantly more frequent in group B (P=0.045). There was no significant difference in the incidence of partial flap necrosis and wound dehiscence, or in the total operation time between the two groups. Superdrainage using the SCIV has the potential to reduce the incidence of venous congestion due to relative venous insufficiency in DCIAPF used for oromandibular reconstruction., (Copyright © 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Long-acting injectable (LAI) antipsychotics improve medication adherence in patients with schizophrenia and extend the duration of therapeutic drug levels but with administration of an increased dose. Real-world mortality data in patients prescribed LAIs are lacking. We conducted a population-based cohort study to estimate and compare the incidence rates of all-cause death and completed suicide in patients with schizophrenia/schizoaffective disorder exposed to LAIs and oral antipsychotics., Methods: Patients with a diagnosis of schizophrenia/schizoaffective disorder between January 1, 2015 and November 30, 2019 were enrolled from the Taiwan National Health Insurance Research Database and linked to Death Registry records. Eligible patients were new antipsychotic users. Relative risks of death for each antipsychotic compared with oral paliperidone were evaluated using a Cox proportional hazard model adjusted for age, sex, Charlson Comorbidity Index, index year, bipolar or major depressive or other mood disorders, mental disorders due to drug use, and baseline hospitalization frequency., Results: There were 228,791.08 person-years of follow-up (mean 2.48 years). The incidence rates of all-cause death in users of LAI paliperidone administered monthly (PP1M) and every 3 months (PP3M) were 7.40/1,000 person-years (95% confidence interval 5.94-9.11) and 9.93 (5.88-15.79), respectively. The incidences of completed suicide were 2.03/1,000 person-years (1.32-2.99) and 3.10 (1.14-6.88), respectively. No significant associations were observed between PP1M and PP3M compared to oral paliperidone in incidences of all-cause death or for completed suicide., Discussion: No increased risk of all-cause death or completed suicide was observed in users of antipsychotic LAIs, including PP1M and PP3M.

Neuropsychiatric lupus (NPSLE), the nervous system presentation of systemic lupus erythematosus (SLE), remains challenging to treat due to its unclear pathogenesis and lack of available targeted therapies. A potential contributor to disease progression is brain tertiary lymphoid structures (TLS); these ectopic lymphoid follicles that can develop tissue-targeted antibodies have recently been described in the MRL/ lpr lupus mouse strain, a classic model for studying NPSLE. The brains of MRL/ lpr mice show a significant increase of CXCL13, an important chemokine in lymphoid follicle formation and retention that may also play a role in the disease progression of NPSLE. The aim of the present study was to inhibit CXCL13 and examine the effect of this intervention on lymphoid formation and the development of neurobehavioral manifestations in lupus mice. Female MRL/ lpr mice were injected with an anti-CXCL13 antibody, an IgG1 isotype-matched antibody, or PBS either three times a week for 12 weeks intraperitoneally (IP) starting at 6-8 weeks of age, or continuously intracerebroventricularly (ICV) with an osmotic pump over a two-week period starting at 15 weeks of age. Cognitive dysfunction and depression-like behavior were assessed at the end of treatment. When treatment was delivered IP, anti-CXCL13 treated mice showed significant improvement in cognitive function when compared to control treated mice. Depression-like behavior was attenuated as well. Furthermore, mice that received anti-CXCL13 by the ICV route showed similar beneficial effects. However, the extent of lymphocyte infiltration into the brain and the general composition of the aggregates were not substantively changed by anti-CXCL13 irrespective of the mode of administration. Nevertheless, analysis of brain gene expression in anti-CXCL13 treated mice showed significant differences in key immunological and neuro-inflammatory pathways that most likely explained the improvement in the behavioral phenotype. Our results indicate that CXCL13 affects the behavioral manifestations in the MRL/ lpr strain and is important to the pathogenesis of murine NPSLE, suggesting it as a potential therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Stock and Putterman.)

Sickle cell disease and β-thalassemia are common monogenic disorders that cause significant morbidity and mortality globally. The only curative treatment currently is allogeneic hematopoietic stem cell transplantation, which is unavailable to many patients due to a lack of matched donors and carries risks including graft-versus-host disease. Genome editing therapies targeting either the BCL11A erythroid enhancer or the HBG promoter are already demonstrating success in reinducing fetal hemoglobin. However, where a single locus is targeted, reliably achieving levels high enough to deliver an effective cure remains a challenge. We investigated the application of a CRISPR/Cas9 multiplex genome editing approach, in which both the BCL11A erythroid enhancer and HBG promoter are disrupted within human hematopoietic stem cells. We demonstrate superior fetal hemoglobin reinduction with this dual-editing approach without compromising engraftment or lineage differentiation potential of edited cells post-xenotransplantation. However, multiplex editing consistently resulted in the generation of chromosomal rearrangement events that persisted in vivo following transplantation into immunodeficient mice. The risk of oncogenic events resulting from such translocations therefore currently prohibits its clinical translation, but it is anticipated that, in the future, alternative editing platforms will help alleviate this risk., Competing Interests: H.P.K. has received support as the inaugural recipient of the José Carreras/E. Donnall Thomas Endowed Chair for Cancer Research and the Stephanus Family Endowed Chair for Cell and Gene Therapy. H.P.K is or was a consultant to and has or had ownership interests with Rocket Pharmaceuticals, Homology Medicines, VOR Biopharma, and Ensoma. H.P.K has also been a consultant to CSL and Magenta. Other authors have no competing interests., (© 2021 The Authors.)

As the proportion of elderly people continues to grow, so does the concern about age-related cognitive decline. Serious games have been developed for cognitive training or treatment, but measuring the activity of the autonomic nervous system (ANS) has not been taken to account. However, cognitive functioning has been known to be heavily influenced by the autonomic nervous system (ANS), and ANS activity can be quantified using heart rate variability (HRV). This paper aims to analyze the physiological response in normal elderly people as they play two types of serious games using HRV features from electrocardiography (ECG). A wearable device designed in-house was used to measure ECG, and the data from this device was pre-processed using digital signal processing techniques. Ten HRV features were extracted, including time-domain, nonlinear, and frequency-domain features. The experiment proceeds as follows: rest for three minutes, play a cognitive aptitude game, rest for another three minutes, followed by two reaction time games. Data from thirty older adults (age: 65.9 ± 7.34; male: 15, female: 15) were analyzed. The statistical results show that there was a significant difference in the HRV between the two types of games. From this, it can be concluded that the type of game has a significant effect on the ANS response. This can be further used in designing games for the elderly, either for training or mood management.

Taiwan was successful in containing the spread of the novel coronavirus (COVID-19) in 2020. One major factor in this success was the compilation and provision of comprehensive information about the pandemic. The present study proposes a pandemic intelligence system that provides data on the number of epidemic prevention professionals in each county and city, as well as daily confirmed cases, the demographics of the confirmed cases, and available resources (negative-pressure room beds and artificial ventilation apparatuses) in hospitals. Furthermore, the system provides the location of pharmacies selling masks and their current inventories, as well as the distribution of crowds at popular tourist destinations and social-distance monitoring. The most frequently used map layer in the thematic map of the pandemic is that of crowd distribution during the study period from March 2020 until the end of the same year. The case study used in this investigation for applying the system is represented by the 4-day weekend for Tomb-Sweeping Day of 2020. Through the real-time analysis of dynamic data and the integration of intelligence, the system offers a clear insight into changes in relevant information and, thus, enables the preemptive deployment of control measures by the county/city governments regarding pandemic management.

Selection of a pre-clinical non-human primate (NHP) model is essential when evaluating therapeutic vaccine and treatment strategies for HIV. SIV and SHIV-infected NHPs exhibit a range of viral burdens, pathologies, and responses to combinatorial antiretroviral therapy (cART) regimens and the choice of the NHP model for AIDS could influence outcomes in studies investigating interventions. Previously, in rhesus macaques (RMs) we showed that maintenance of mucosal Th17/Treg homeostasis during SIV infection correlated with a better virological response to cART. Here, in RMs we compared viral kinetics and dysregulation of gut homeostasis, defined by T cell subset disruption, during highly pathogenic SIVΔB670 compared to SHIV-1157ipd3N4 infection. SHIV infection resulted in lower acute viremia and less disruption to gut CD4 T-cell homeostasis. Additionally, 24/24 SHIV-infected versus 10/19 SIV-infected animals had sustained viral suppression <100 copies/mL of plasma after 5 months of cART. Significantly, the more profound viral suppression during cART in a subset of SIV and all SHIV-infected RMs corresponded with less gut immune dysregulation during acute SIV/SHIV infection, defined by maintenance of the Th17/Treg ratio. These results highlight significant differences in viral control during cART and gut dysregulation in NHP AIDS models and suggest that selection of a model may impact the evaluation of candidate therapeutic interventions for HIV treatment and cure strategies.

Purpose: The present study retrospectively evaluated the effectiveness and safety of iodine-125 interstitial brachytherapy for treatment of primary locally advanced adenoid cystic carcinoma (ACC) of the base of tongue (BOT)., Material and Methods: This study was a retrospective analysis of data of 19 patients with ACC, who were treated with iodine-125 interstitial brachytherapy between March 2008 and April 2018. Overall survival (OS), disease-free survival (DFS), local control (LC), and radiation-related toxicities were determined. Factors affecting the outcomes were evaluated., Results: Six males and 13 females were included in our study, with a median follow-up time of 35 months. 3- and 5-year OS rates were 71.5% and 47.6%, respectively. 3- and 5-year LC rates were 88.5% and 34.5%, respectively. 3- and 5-year DFS rates were 54.7% and 21.9%, respectively. A significant difference was observed in patients with or without brain metastases for OS rate. No severe acute toxicity was observed, while severe late toxicity was observed in one patient., Conclusions: The results suggest that iodine-125 interstitial brachytherapy is an effective and safe option for the treatment of primary locally advanced ACC of the base of the tongue, with reasonably satisfactory LC and OS., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Termedia.)

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.

For decades, scientists have been trying to solve the problem of dementia, with no cure currently available. Semantic-lexical impairment is well established as the early critical sign of dementia, although there are still gaps in knowledge that must be investigated. In this study, we used fMRI to observe the neural activity of 31 subjects, including 16 HC (Healthy Control) and 15 AD (Alzheimer's Disease), who participated in the naming task. The neuropsychology profile of HC (Healthy Control) and AD (Alzheimer's Disease) are discussed in this study. The involvement of FG (Fusiform Gyrus) and IFG (Inferior Frontal Gyrus) shows dominant activation in both of the groups. We observed a decrease in neural activity in the AD group, resulting in semantic deficit problems in this preliminary study. Furthermore, ROI analysis was performed and revealed both hyperactivation and hypoactivation in the AD group. The compensatory mechanism demonstrated during the task, due to the effort required to identify an animal's name, represents the character profile of AD.

Rhus chinensis is an important resource plant. The aqueous extract of R. chinensis roots or stems was to produce Shuguantong Syrup, which is mainly used for the treatment of coronary heart disease and angina pectoris with definite curative effect. On this basis, the crude phenolic part of R. chinensis prepared by macroporous resin was evaluated for the cardio protective effect against myocardial ischemia in mice. The results showed that the phenolic part group with oral administration at the dosages of 190.8-381.6 mg·kg~(-1), compared with the model group, reduced the values of left ventricular end systolic diameter(LVEDs) and the left ventricular end diastolic diameter(LVEDd), and increased the cardiac ejection fraction(EF) and left ventricular fractional shortening(FS) rate, which could effectively improve cardiac function and exert its anti-myocardial ischemia effect, and reduce the rising levels of creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH) in serum. HE staining showed that the phenolic part group reduced the infiltration of myocardial inflammatory cells and alleviated the degree of myocardial fibrosis and collagen deposition. TUNEL staining showed that the blue-green fluorescence of the phenolic part group decreased successively, and the degree of myocardial cell apoptosis was reduced. Immunohistochemical staining suggested that it could reduce the number of positive cells for p53 protein expression and significantly improve myocardial cell damage. All above data suggested that the phenolic part group had an anti-mycardial ischemis effect. Related mechanism studies revealed that the crude phenolic part could regulate the expressions of the p53 gene(p53), Bcl-2-associated X protein(Bax), B lymphoma-2 gene(Bcl-2), and caspase-3 protein(caspase-3) in myocardial tissue, suggesting that it could reduce cardiac remodeling and myocardial ischemic damage, and improve cardiac function by inhibiting myocardial apoptosis.This research laid a foundation for the elucidation of the pharmacological ingredients R. chinensis.

Integrins are a large family of heterodimeric cell adhesion molecules composed of α and β subunits. Through interaction with their specific ligands, integrins mediate cell-cell and cell-extracellular matrix interactions. Via outside-in signaling, integrins can recruit cytoplasmic proteins to their intracellular domains and then cluster into supramolecular structures and trigger downstream signaling. Integrin activation is associated with a global conformation rearrangement from bent to extended in ectodomains and the separation of α and β subunit cytoplasmic domains. During cell migration, integrins regulate the focal adhesion dynamics and transmit forces between the extracellular matrix and the cell cytoskeleton. In tumor microenvironment, integrins on multiple kinds of cells could be activated, which modulates cell migration into tumor and contributes to angiogenesis and tumor metastasis. Here, we review the mechanism of integrin activation, dynamics of focal adhesions during cell migration and tumor metastasis.

The carbon-silicon switch strategy has become a key technique for structural optimization of drugs to widen the chemical space, increase drug activity against targeted proteins, and generate novel and patentable lead compounds. Flubeneteram, targeting succinate dehydrogenase (SDH), is a promising fungicide candidate recently developed in China. We describe the synthesis of novel SDH inhibitors with enhanced fungicidal activity to enlarge the chemical space of flubeneteram by employing the C-Si switch strategy. Several of the thus formed flubeneteram-silyl derivatives exhibited improved fungicidal activity against porcine SDH compared with the lead compound flubeneteram and the positive controls. Disease control experiments conducted in a greenhouse showed that trimethyl-silyl-substituted compound W2 showed comparable and even higher fungicidal activities compared to benzovindiflupyr and flubeneteram, respectively, even with a low concentration of 0.19 mg/L for soybean rust control. Furthermore, compound W2 encouragingly performed slightly better control than azoxystrobin and was less active than benzovindiflupyr at the concentration of 100 mg/L against soybean rust in field trials. The computational results showed that the silyl-substituted phenyl moiety in W2 could form strong van der Waals (VDW) interactions with SDH. Our results indicate that the C-Si switch strategy is an effective method for the development of novel SDH inhibitors.

Objective: The aim of this study was to investigate the effectiveness and safety of surgery combined with 125 I seed brachytherapy for treatment of carcinoma ex pleomorphic adenoma (CXPA) of the parotid gland and to identify the factors associated with prognosis., Study Design: We conducted a retrospective analysis of data of patients with CXPA of the parotid gland treated with surgery plus 125 I seed brachytherapy at the Peking University School of Stomatology Hospital between December 2003 and July 2018., Results: Fifty-five patients (median age, 51 years) were included in the study. Median follow-up was 50.5 months. The 3-, 5-, and 10-year overall survival rates were 91.1%, 91.1%, and 81.5%, respectively. The 3-, 5-, and 10-year local control rates were all 85.2%. Grades 1-3 adverse effects occurred in 22 patients; no grade 4 reactions occurred. T stage, N stage, tumor invasiveness, perineural invasion, and surgical margins significantly affected local control rates. Lymph node metastasis and perineural invasion were independent predictors of poor local control. Lymph node metastasis was an independent predictor of poor survival., Conclusions: Surgery plus 125 I seed brachytherapy appears to be an effective and safe treatment for CXPA of the parotid gland. T stage, N stage, tumor invasiveness, and perineural invasion are factors influencing prognosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The experiences of professionals in well-established recovery-oriented programs are valuable for professionals in similar practice settings. This study explored professionals' experiences with providing recovery-oriented services in community psychiatric rehabilitation organizations., Methods: Semi-structured interviews were conducted with 14 professionals from five recovery-oriented psychiatric rehabilitation organizations in Taiwan. The interviews were recorded and transcribed verbatim. Thematic analysis was used for the qualitative data analysis., Results: The analyses documented three main themes with 13 subthemes. Recovery-oriented service implementation included seven subthemes: Enabling clients to set their own goals and make decisions, using a strengths-based approach, establishing partnerships with clients, improving individuals' self-acceptance, encouraging community participation, seeking family, peer, and organizational support, and building team collaboration. Problems with implementing recovery-oriented services included limited policy and organizational support, a lack of understanding of recovery among professionals, stigma, clients' lack of motivation or self-confidence in their own ability to achieve recovery, and passive or overprotective family members. Strategies to resolve implementation problems included policy changes and organizational support, improving the recovery competence and confidence of professionals, and family and public education., Conclusions: To date, this is the first known study examining the perspectives of mental health professionals who have experience implementing recovery-oriented services in Asia. The participants identified family collaboration, anti-stigma efforts, and changes in policy and attitudes as critical to successful implementation and delivery of recovery-oriented services.

Objective: To retrospectively review the impact of the outbreak of coronavirus disease 2019 (COVID-19) on services in the oral emergency room., Materials and Methods: A statistical analysis of epidemiological characteristics and the patients' diagnoses and treatments in the Emergency Department of Peking University Hospital of Stomatology during the outbreak of COVID-19 in 2020 compared with those in 2019 in Beijing, China., Results: There were fewer total visits in 2020 than in 2019 (P = 0.001), and the proportions of patients who were children, adolescents and elderly people were lower in 2020 than in 2019 (P < 0.001). The proportions of patients with acute toothache and infections were higher in 2020 than in 2019, and the proportions of patients with maxillofacial trauma and non-emergencies were lower in 2020 than in 2019 (P < 0.001). Drug treatment for acute pulpitis was used more often in 2020 than in 2019, and endodontic treatment and examination consultations were less common in 2020 than in 2019 (P = 0.022)., Conclusions: The outbreak of COVID-19 affected the patient population and structure of disease types and oral services in the emergency room. The number of visits to the oral emergency room and the proportions of the patients who were children, adolescents and elderly people were reduced, meanwhile the percentage of emergency cases, except trauma, and conservative treatments increased during the outbreak of COVID-19., Competing Interests: Conflict of interest The authors have no conflict of interest in relation to this work., (Copyright © 2021. Published by Elsevier Inc.)

We wished to investigate the outcome of surgery combined with external-beam radiotherapy (EBRT) or brachytherapy ( 125 I seeds) for the treatment of primary adenoid cystic carcinoma (ACC) of the oral and maxillofacial region. Data of patients with primary ACC were reviewed retrospectively. Patients were divided into EBRT and brachytherapy groups. Wide tumor excision was done to achieve negative margins. Standard radiotherapy in the EBRT group was 60 Gy. A treatment-planning system was used to create implantation plans with a prescribed dose of 60-120 Gy and 125 I seeds were implanted postoperatively. Kaplan-Meier method and log-rank tests were used to analyze local control and survival. The median duration of followup was 66.1 and 46.8 months for the EBRT group and brachytherapy group, respectively. There was no significant difference in local control, control of metastasis to regional lymph nodes, or control of distant metastasis between the two groups. There was no significant difference in overall survival, disease-specific survival, or disease-free survival in the two groups at 3 years and 5 years. The prevalence of complications in the brachytherapy group was lower than that in the EBRT group. Both methods elicited good treatment effects, but the prevalence of adverse events was lower in the brachytherapy group., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Human herpes simplex viruses (HSV) 1 and 2 are extremely common human pathogens with overlapping disease spectra. Infections due to HSV-1 and HSV-2 are distinguished in clinical settings using sequence-based "typing" assays. Here we describe a case of HSV mistyping caused by a previously undescribed HSV-1 × HSV-2 recombination event in UL27, the HSV gene that encodes glycoprotein B. This is the first documented case of HSV mistyping caused by an HSV-1 × HSV-2 recombination event and the first description of an HSV interspecies recombination event in UL27, which is frequently used as a target for diagnostics and experimental therapeutics. We also review the primer and probe target sequences for a commonly used HSV typing assay from nearly 700 HSV-1 and HSV-2 samples and find that about 4% of HSV-1 samples have a single nucleotide change in at least one of these loci, which could impact assay performance. Our findings illustrate how knowledge of naturally occurring genomic variation in HSV-1 and HSV-2 is essential for the design and interpretation of molecular diagnostics for these viruses.

Objective: In systemic lupus erythematosus (SLE), widespread T cell infiltration into target organs contributes to inflammation and organ damage. Autoreactive T cells become aberrantly activated in this disease due to dysfunctional T cell receptor signaling that lowers the activation threshold. Characterizing the T cell repertoire can provide further insight into the specific homing and proliferation of these T cells into lupus target organs. In the spontaneous lupus model, MRL/lpr, the TCR repertoire has not been fully elucidated, especially for T cells infiltrating the brain. Our aim was to investigate and compare the TCR repertoire between MRL/lpr mice and its congenic controls, MRL/MpJ, and within MRL/lpr tissues. Methods: Spleen, salivary gland, and brain choroid plexus were isolated from female MRL/lpr mice and MRL/MpJ mice. The TCRβ CDR3 region was analyzed by multiplex PCRs and sequencing. Results: Significant differences were seen not only between the MRL/lpr and MRL/MpJ spleens, but also between MRL/lpr tissues. The TCR repertoire in MRL/lpr choroid plexus tissues had significantly increased clonality and sequence homology compared to MRL/lpr spleen and salivary gland. The consensus sequence, CASSQDWGGYEQYFF, was identified in the MRL/lpr choroid plexus repertoire. Conclusions: The TCR repertoire in lupus prone mice is not uniform between target organs, and suggests that T cells are specifically recruited into the choroid plexus of MRL/lpr mice. Further studies are needed to determine the antigen specificities for these infiltrating T cells in target organs of lupus mice, and their possible contribution to the pathogenesis of neuropsychiatric disease and other lupus manifestations., (Copyright © 2020 Moore, Huang, Jain, Chalmers, Macian and Putterman.)

Background: Acinic cell carcinoma (AciCC) is rare in children; therefore, reaching a consensus on its management is challenging and radiotherapy is limited by concerns about long-term toxicity. The purpose of this study is to analyze the effectiveness and safety of surgery plus postoperative 125 I interstitial brachytherapy (IBT) for children and adolescents with AciCC of the parotid gland (PG) treated at a single institution., Procedure: Sixteen patients ≤ 18 years old with AciCC of the PG treated with surgery plus 125 I IBT from 2007 to 2018 were included. Surgery was the primary treatment; ten patients underwent total gross excision and six subtotal gross excision. The matched peripheral dose was 60-120 Gy. Overall survival, disease-free survival (DFS), local control rate, distant metastasis, and radiation-associated toxicities were analyzed, and factors influencing outcomes were evaluated., Results: During follow-up (1.8-12.6 years; mean, 6.3 years), lymph node metastasis was observed in one case, 2.6 years after 125 I IBT treatment. The five-year overall and DFS rates were 100% and 91.7%, respectively. On univariate analysis, tumor size ≥ 3 cm (100% vs 50%; P = 0.025) and extraglandular extension (100% vs 50%; P = 0.025) were significant prognostic indicators for DFS. No severe radiation-associated complications occurred., Conclusions: Children and adolescents with AciCC of the PG with high-risk features can be managed using surgery plus postoperative 125 I IBT with excellent local control. Radiation-related complications were minor. Patients with facial nerve involvement can have their facial nerves preserved. Residual tumors can be safely managed using adjuvant 125 I IBT., (© 2020 Wiley Periodicals, Inc.)

Nearly 400,000 people worldwide are known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beginning in December 2019. The virus has now spread to over 168 countries including the United States, where the first cluster of cases was observed in the Seattle metropolitan area in Washington. Given the rapid increase in the number of cases in many localities, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we evaluated assays using seven different primer-probe sets and one assay kit. We found that the most sensitive assays were those that used the E-gene primer-probe set described by Corman et al. (V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25:2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set developed by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer-probe set or kit used. These results will provide valuable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide., (Copyright © 2020 Nalla et al.)

Purpose: The aim of this study was to evaluate the feasibility and diagnostic accuracy of core needle biopsy (CNB) in patients with focal fluorodeoxyglucose (FDG) uptake on positron emission tomography/computed tomography (PET/CT) in deep regions of the head and neck, with the guidance of infrared navigation integrated with PET., Materials and Methods: Patients with suspected primary or recurrent malignancies of the head and neck on PET/CT, from June 2016 to December 2018, were included. Before CNB, the region of interest was delineated and the ideal needle entry points, target sites, and a number of trajectories were designed on iPlan CMF 3.0. CNB was performed with the guidance of infrared navigation integrated with PET, according to the pre-plan. Sensitivity and diagnostic accuracy were analyzed by comparing the biopsy results with the final diagnosis., Results: Thirty-one consecutive patients were included. Among the 31 lesions, 18 were skull base, six were infratemporal fossa, and seven were maxillary region. The median values for SUVmax, SUVmean, and MTV were 6.09 (range: 1.43-24.67), 3.41 (range: 0.38-20.96), and 25.83 (range: 3.54-361.94) for the 31 lesions, respectively. Combined needle approaches were employed, including temporal (nine), subzygomatic (19), paramaxillary (11), and retromandibular (16) approaches. The depths of the 31 deep-region lesions, measured from the needle entry site on the skin to the target point, ranged from 1.33 cm to 7.82 cm (median 4.25 cm). There were three non-diagnostic lesions resulting from CNB, and these were all skull base. The diagnostic accuracy was 90.3%, while the sensitivity was 88%. According to the binary logistic regression for the final diagnosis, the only significant parameter was SUVmax., Conclusion: With the guidance of navigation integrated with PET, CNB is a feasible and accurate diagnostic modality, which is also an alternative to open biopsy in patients with suspected primary or recurrent malignancies in deep regions of the head and neck on PET/CT., (Copyright © 2020 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

The genus Syringa, belonging to the family Oleaceae, are distributed naturally in the European and Asian regions.This genus is composed of more than 20 species worldwide, among which about 16 species including 10 endemic ones are discovered in China.The Syringa sp.are extensively used as herbal medicine and ornamental aspects, such as the roots and stems of S. pinnatifolia, which is one of the typical Mongolian folk medicines in China for the treatment of cardiovascular and pulmonary symptoms. As a continuous research following the previous summary in 2015, the present reriew describes the phytochemical and pharmacological progress of the genus, which hopes to provide a valuable reference to its research, development and clinic application.