Potential COVID-19 remedies from repurposed drugs and herbal small RNAs.

To date, SARS-CoV-2 has caused millions of deaths, but the choice of treatment is limited. We previously established a platform for identifying Food and Drug Administration (FDA)-approved repurposed drugs for avian influenza A virus infections that could be used for coronavirus disease 2019 (COVID-19) treatment. In this study, we analyzed blood samples from two cohorts of 63 COVID-19 patients, including 19 patients with severe disease. Among the 39 FDA-approved drugs we identified for COVID-19 therapy in both cohorts, 23 drugs were confirmed by literature mining data, including 14 drugs already under COVID-19 clinical trials and 9 drugs reported for COVID-19 treatments, suggesting the remaining 16 FDA-approved drugs may be candidates for COVID-19 therapy. Additionally, we previously reported that herbal small RNAs (sRNAs) could be effective components in traditional Chinese medicine (TCM) for treating COVID-19. Based on the abundance of sRNAs, we screened the 245 TCMs in the Bencao (herbal) sRNA Atlas that we had previously established, and we found that the top 12 TCMs for COVID-19 treatment was consistent across both cohorts. We validated the efficiency of the top 30 sRNAs from each of the top 3 TCMs for COVID-19 treatment in poly(I:C)-stimulated human non-small cell lung cancer cells (A549 cells). In conclusion, our study recommends potential COVID-19 remedies using FDA-approved repurposed drugs and herbal sRNAs from TCMs.

Acute epicardial pulmonary vein reconnection: Nondurable transmural lesion or late manifestation of conduction through intercaval bundle.

INTRODUCTION: Acute pulmonary vein reconnection (PVR) via epicardial fibers can be found during observation period after PV isolation, the characteristics and related factors have not been fully studied. We aimed to investigate the prevalence, locations, electrogram characteristics, and ablation parameters related to acute epicardial pulmonary vein reconnection (AEPVR). METHODS: Acute PVR was monitored during observation period after PV isolation. AEPVRs were mapped and distinguished from endocardial conduction gaps. The clinical, electrophysiological characteristics and lesion set parameters were compared between patients with and without PVR. They were also compared among AEPVR, gap-related reconnection, and epicardial PVR in repeat procedures. RESULTS: A total of 56.1% acute PVR were AEPVR, which required a longer waiting period (p < .001) than endocardial gap. The majority of AEPVR were connections from the posterior PV carina to the left atrial posterior wall, followed by late manifestation of intercaval bundle conduction from the right anterior carina to right atrium. AEPVR was similar to epicardial PVR in redo procedures in distribution and electrogram characteristics. Smaller atrium (p < .001), lower impedance drop (p = .039), and ablation index (p = .028) on the posterior wall were independently associated with presence of AEPVR, while lower interlesion distance (p = .043) was the only predictor for AEPVR in acute PVR. An integrated model containing multiple lesion set parameters had the highest predictive ability for AEPVR in receiver operating characteristics analysis. CONCLUSIONS: Epicardial reconduction accounted for the majority of acute PVR. AEPVR was associated with anatomic characteristics and multiple ablation-related parameters, which could be explained by nondurable transmural lesion or late manifestation of conduction through intercaval bundle.

Smoking-related cancer death among men and women in an ageing society (China 2020-2040): a population-based modelling study.

BACKGROUND: China is experiencing a postpeak smoking epidemic with accelerating population ageing. Understanding the impacts of these factors on the future cancer burden has widespread implications. METHODS: We developed predictive models to estimate smoking-related cancer deaths among men and women aged ≥35 years in China during 2020-2040. Data sources for model parameters included the United Nations World Population Prospects, China Death Surveillance Database, national adult tobacco surveys and the largest national survey of smoking and all causes of death to date. The main assumptions included stable sex-specific and age-specific cancer mortality rates and carcinogenic risks of smoking over time. RESULTS: In a base-case scenario of continuing trends in current smoking prevalence (men: 57.4%-50.5%; women: 2.6%-2.1% during 2002-2018), the smoking-related cancer mortality rate with population ageing during 2020-2040 would rise by 44.0% (from 337.2/100 000 to 485.6/100 000) among men and 52.8% (from 157.3/100 000 to 240.4/100 000) among women; over 20 years, there would be 8.6 million excess deaths (0.5 million more considering former smoking), and a total of 117.3 million smoking-attributable years of life lost (110.3 million (94.0%) in men; 54.1 million (46.1%) in working-age (35-64 years) adults). An inflection point may occur in 2030 if smoking prevalence were reduced to 20% (Healthy China 2030 goal), and 1.4 million deaths would be averted relative to the base-case scenario if the trend were maintained through 2040. CONCLUSIONS: Coordinated efforts are urgently needed to curtail a rising tide of cancer deaths in China, with intensified tobacco control being key.

F0 range instead of F0 slope is the primary cue for the falling tone of Mandarin.

It has been well known that rising/falling pitch is employed to distinguish the rising (R) or falling (F) tones from the high-level (H) tone in Mandarin, but whether F0 range or F0 slope is the more critical F0 cue to perception is still inconclusive. To clarify this issue quantitatively, we took the F tone as the test case, and conducted two-alternative forced choice identification tests on two types of two-dimensional high-level-falling (H-F) tonal continua, one of which was manipulated along F0 range and duration ("F0 range continuum") while the other along F0 slope and duration ("F0 slope continuum"). Experimental results indicated that F0 range was the primary cue because it resulted in a more robust (less duration-dependent) perceptual boundary than F0 slope. Meanwhile, the perceptual boundary in F0 range was not fully independent of but mildly modulated by duration, suggesting that duration (or equivalently, F0 slope) played a supplementary role in identifying the H-F tonal contrast.

Nationwide gastric cancer prevention in China, 2021-2035: a decision analysis on effect, affordability and cost-effectiveness optimisation.

OBJECTIVE: To project future trajectories of the gastric cancer (GC) burden in China under different scenarios of GC prevention and identify strategies to improve affordability and cost-effectiveness. DESIGN: Using a cohort of Chinese men and women born during 1951-1980, we assumed that different prevention strategies were conducted, including eradication of Helicobacter pylori (Hp) and endoscopy screening (one-time, annual, biennial, triennial or stratified according to personal risk). We performed a literature search to identify up-to-date data and populate a Markov model to project the number of new GC cases and deaths during 2021-2035, as well as resource requirements and quality-adjusted life-years (QALYs). We examined the impacts of general (among the whole population) and targeted (high-risk population) prevention. RESULTS: During 2021-2035, 10.0 million new GC cases and 5.6 million GC deaths would occur, with 7.6%-35.5% and 6.9%-44.5%, respectively, being avoidable through various prevention strategies. Relative to the status quo, Hp eradication was a cost-saving strategy. General annual screening dominated other screening strategies, but cost more than CNY 70 000 per QALY gained (willingness-to-pay) compared with Hp eradication. Among endoscopy strategies, targeted screening resulted in 44%-49% lower cost per QALY gained over the status quo than general screening. Among high-risk population, tailoring the screening frequency according to personal risk could reduce endoscopy-related resources by 22% compared with biennial screening and by 55% compared with annual screening, CONCLUSION: Our findings provide important input for future decision-making and investment, highlighting the need and feasibility for China to include GC prevention in its national health plans.

Split accessory pathway potentials in a patient with antidromic AVRT.

INTRODUCTION: Accessory pathway potential often indicates a highly effective ablation target in Wolff-Parkinson-White syndrome. METHODS: A 27-year-old female presenting with palpitation underwent an electrophysiology study, who had mild pre-excitation in surface ECG. RESULTS: An accessory pathway with weak anterograde conduction was found. During isoproterenol infusion, the delta wave became prominent, an antidromic AV reentrant tachycardia was then induced. When the pathway was mapped, widely split double pathway potentials were observed at the 12 o'clock site of the tricuspid annulus during mild pre-excitation, demonstrating an example of intra-pathway conduction delay. Ablation at the site caused accelerated pathway rhythm and eliminated the pathway, rendering the tachycardia noninducible. CONCLUSION: Split pathway potentials can reflect slow conduction in patients with preexcitation.

Simultaneous full set of three-input canonical logic units in a single nonlinear device for an all-optical programmable logic array.

All-optical canonical logic units-based programmable logic array (CLUs-PLA) is an important combinational logic device owing to its flexibility and user-defined feature. However, the limited number of three-input CLUs generated in a single nonlinear device hinders their practical application. In this study, we overcome this limitation and experimentally demonstrate the simultaneous generation of a full set of three-input CLUs in only one nonlinear device. By performing bidirectional four-wave mixing (FWM) and wavelength spacing optimization, the all-optical three-input PLA with a full set of CLUs enables arbitrary functions. We experimentally demonstrate the implementation of a series of combinational logic functions including, user-defined logic functions, full adder, and full subtractor, exhibiting error-free performances for all logic operations at 40 Gb/s. The scheme can reduce the number of nonlinear devices in CLUs-PLA, which simplifies the computing system and reduces power consumption. Therefore, the scheme has great potential for future high-speed optical computing systems.

Seven-channel all-optical reconfigurable canonical logic units multicasting at 40 Gb/s based on a nonlinearity-enhanced silicon waveguide.

All-optical canonical logic unit (CLU) is the basic building block of high-speed optical logic operation and complex optical computing. By utilizing the parallelism of optical signals, multichannel multicasting of all-optical CLUs can expand the capacity of the computing system effectively. Here, we propose and experimentally demonstrate the 40 Gb/s all-optical reconfigurable two-input CLUs generated in seven wavelength channels via four-wave mixing (FWM) in the nonlinearity-enhanced silicon waveguide. By introducing reverse-biased PIN junctions to reduce nonlinear loss, the output power of converted light can be increased over 10 dB. Moreover, pumped by two optical signals and a continuous wave beam, a full set of reconfigurable CLUs is multicasted in seven parallel wavelength channels. All logic signals with error-free performance are realized. Attributing to the rate transparency of FWM and parallel multicasting of logic functions, the proposed scheme offers more flexibility and expandability in future high-speed optical logic processing and complex optical computing.

Generating real-world evidence compatible with evidence from randomized controlled trials: a novel observational study design applicable to surgical transfusion research.

BACKGROUND: Numerous observational studies have revealed an increased risk of death and complications with transfusion, but this observation has not been confirmed in randomized controlled trials (RCTs). The "transfusion kills patients" paradox persists in real-world observational studies despite application of analytic methods such as propensity-score matching. We propose a new design to address this long-term existing issue, which if left unresolved, will be deleterious to the healthy generation of evidence that supports optimized transfusion practice. METHODS: In the new design, we stress three aspects for reconciling observational studies and RCTs on transfusion safety: (1) re-definition of the study population according to a stable hemoglobin range (gray zone of transfusion decision; 7.5-9.5 g/dL in this study); (2) selection of comparison groups according to a trigger value (last hemoglobin measurement before transfusion; nadir during hospital stay for control); (3) dealing with patient heterogeneity according to standardized mean difference (SMD) values. We applied the new design to hospitalized older patients (aged ≥60 years) undergoing general surgery at four academic/teaching hospitals. Four datasets were analyzed: a base population before (Base Match-) and after (Base Match+) propensity-score matching to simulate previous observational studies; a study population before (Study Match-) and after (Study Match+) propensity-score matching to demonstrate effects of our design. RESULTS: Of 6141 older patients, 662 (10.78%) were transfused and showed high heterogeneity compared with those not receiving transfusion, particularly regarding preoperative hemoglobin (mean: 11.0 vs. 13.5 g/dL) and intraoperative bleeding (≥500 mL: 37.9% vs. 2.1%). Patient heterogeneity was reduced with the new design; SMD of the two variables was reduced from approximately 100% (Base Match-) to 0% (Study Match+). Transfusion was related to a higher risk of death and complications in Base Match- (odds ratio [OR], 95% confidence interval [CI]: 2.68, 1.86-3.86) and Base Match+ (2.24, 1.43-3.49), but not in Study Match- (0.77, 0.32-1.86) or Study Match+ (0.66, 0.23-1.89). CONCLUSIONS: We show how choice of study population and analysis could affect real-world study findings. Our results following the new design are in accordance with relevant RCTs, highlighting its value in accelerating the pace of transfusion evidence generation and generalization.

Anatomy-based characteristics of far-field SVC electrograms in right superior pulmonary veins after isolation.

Background. Far-field electrograms from superior vena cava (SVC) can be present in right superior pulmonary vein (RSPV) after pulmonary vein (PV) isolation. Objectives. To analyze the characteristics of far-field SVC potentials in RSPV after PV isolation and the local anatomy difference between patients with and without the potentials. Methods. Patients undergoing PV isolation were retrospectively reviewed, contrast-enhanced computed tomography (CT) was performed before procedure for observing the anatomical relationship between RSPV and SVC. The prevalence and characteristics of far-field SVC electrograms were described and compared to far-field left atrial potentials at the nearest point along the linear ablation lesion. The anatomical proximity of RSPV and SVC on a 2-dimensional horizontal CT view was compared between patients with and without far-field SVC potentials. Results. Far-field SVC electrograms were observed in 35/92(38%) patients with an amplitude of 0.24 ± 0.11 mV and a major deflection slope of 0.051 ± 0.036 mV, both significantly higher than far-field left atrial electrograms (p < .001). In patients with far-field SVC electrograms, 83% had connected RSPV-SVC, defined as distance between RSPV and SVC endocardium less than 3 mm at the layer of RSPV ostium roof, while in patients without far-field SVC electrograms, 70% had disconnected RSPV-SVC. Conclusions. Far-field SVC electrograms appeared in RSPV had a prevalence higher than previously reported and a sharper major deflection compared to far-field left atrial electrograms. Connected RSPV-SVC on CT was associated with the presence of far-field SVC electrograms.

Pseudo normalization of H-V interval due to intra-His block in a patient with fasciculoventricular accessory pathway.

A 57-year-old male suffering from cardiogenic syncope was found to have preexcited QRS on surface ECG at admission. A dual-chamber ICD was implanted after discovering intermittent high degree A-V block and ventricular tachycardia during hospitalization. An EP study was performed 2 days later. Fasciculoventricular accessory pathway was diagnosed based on the fixed H-V interval with different A-H interval when atrial activation conducted to ventricle. However, the H-V interval was normal, which can be explained by intra-His block based on the findings of two split His potentials, the second of which was closely followed by local ventricular electrogram. The conduction delay in His bundle led to pseudo normalization of H-V interval.

Occurrence and Estrogenic Potency of Bisphenol Analogs in Sewage Sludge from Wastewater Treatment Plants in Central China.

Land application is suggested to be the most economical sludge disposal method but is also a potential source of bisphenol analogs (BPs) to the environment. In this study, BP concentrations in sewage sludge from Henan province ranged from 15.1 to 2237 ng g-1 dw. BPA was dominant with mean concentration of 140 ng g-1 dw, followed by BPS (mean 43.4 ng g-1 dw), BPF (mean 7.98 ng g-1 dw), BPAF (mean 1.04 ng g-1 dw), BPAP (mean 0.88 ng g-1 dw), BPB (mean 0.38 ng g-1 dw), and BPZ (mean 0.33 ng g-1 dw). Apart from BPB, no significant correlations were found between BPs and wastewater treatment plants characteristics, probably because adsorption does not play a major role in the removal of BPs. The estimated total emission flux of BPs from sludge-amended soils are approximately 62.7 kg year-1. BPA is the largest contributor with emission flux of 45.3 kg year-1. Hazard quotient values for BPs in sludge-amended soils are 3-6 orders of magnitude lower than 1 with total 17ß-estradiol equivalents ranging from 0.33 to 26.8 pg g-1 E2EQ dw. Overall, although being partially replaced by other analogs, BPA is still widely used in Henan province.

Long Coding RNA XIST Contributes to Neuronal Apoptosis through the Downregulation of AKT Phosphorylation and Is Negatively Regulated by miR-494 in Rat Spinal Cord Injury.

Recent evidence has suggested that long non-coding RNAs (lncRNAs) may play a significant role in the pathogenesis of several neurological diseases, including spinal cord injury (SCI). However, little is known about the role of lncRNAs in SCI. The aim of the present study was to evaluate the potential functions of lncRNAs in SCI and to identify the underlying mechanisms of action. We firstly analyzed Gene Expression Omnibus (GEO) datasets to investigate aberrantly-expressed lncRNAs which might be involved in the pathogenesis of SCI. The long non-coding RNA X-inactive specific transcript (XIST) was found to be one of the most significantly upregulated lncRNAs in the GEO dataset analysis, and is associated with apoptosis. We, therefore, selected this as a candidate lncRNA and investigated its function. We found that knockdown of lncRNA-XIST by Lv-shRNA had a prominent protective effect on SCI recovery by suppressing apoptosis through reactivation of the PI3K/AKT signaling pathway in rat spinal cord tissue. In particular, our results suggested that lncRNA-XIST may act as a competitive endogenous RNA, effectively becoming a sink for miR-494, leading to derepression of its target gene, phosphatase and tensin homolog deleted on chromosome ten (PTEN). In addition, an inverse relationship between lncRNA-XIST and miR-494 was observed in spinal cord tissues of SCI rats. Further study demonstrated that antagomiR-494 could reverse the protective effects of lncRNA-XIST knockdown on SCI rats through blocking the PTEN/PI3K/AKT signaling pathway. These results suggested that lncRNA-XIST knockdown may play an important role in limiting neuronal apoptosis in rats following SCI, and that the observed protective effects of lncRNA-XIST knockdown might have been mediated by its regulation on the phosphorylation of AKT by competitively binding miR-494. These findings have revealed, for the first time, the importance of the XIST/miR-494/PTEN/AKT signaling axis in the pathogenesis of SCI and suggest that lncRNA-XIST may be a promising molecular target for SCI therapy.

Identifying hedgehog signaling specific microRNAs in glioblastomas.

Aberrant activation of hedgehog (Hh) signaling pathway plays an important role in the development and proliferation of glioblastoma (GBM) cells. However, its mechanism remains unknown. MicroRNAs (miRNAs) are short non-coding RNA molecules which are involved in the post-transcriptional regulation of genes, and enrolled in signaling transduction network in tumors. This study was designed to investigate the role of miRNAs targeting the Hh signaling pathway in GBMs. According to the expression level of Gli1 mRNA measured by real time PCR, GBM samples were assigned to Gli1 high or low expression group. MiRNA microarray was applied to screen the dysregulated miRNA. As a result, 17 miRNAs were differentially expressed between Gli1 high expression and low expression groups (p < 0.005). Thirteen miRNAs including miR-125b-1 were downregulated, while only 4 miRNAs including miR-144 were upregulated in Gli1 high expression group. In summary, our study presents a subset of miRNAs which target the Hh signaling pathway in GBMs, and throws some light on the aberrant activation mechanism.

[Prognostic analyses of intramedullary high grade astrocytomas].

OBJECTIVE: To explore the prognostic factors of intramedullary high grade astrocytomas. METHODS: Retrospective analyses were conducted for 21 surgical patients with high grade astrocytoma in spinal cord during 2008 to 2012 at our hospital. Their preoperative and postoperative profiles were recorded and evaluated by modified McCormick classification scheme. RESULTS: Their median age was 32.5 years. There were anaplastic astrocytoma (n = 14) and glioblastoma (n = 7). The prognoses of high grade astrocytomas were correlated with pathology grade and MIB-1 index. No statistic significance existed in age, gender, McCormick score, extent of resection, radiotherapy or chemotherapy. CONCLUSION: Intramedullary high grade astrocytoma has a low incidence, but its outcome is poor. Once definitely diagnosed, operation is recommended as early as possible. Frozen pathology should be performed to determine the extent of resection. After operation, chemotherapy and radiotherapy are also suggested.

[Effects of physical factors on neck or shoulder pain and low back pain of adolescents].

OBJECTIVE: To explore the incidence of self-reported neck or shoulder pain (NSP) and lower back pain (LBP) among Chinese adolescents in Shanghai and identify the influencing factors for the incidences of NSP and LBP. METHODS: A total of 3 600 students were selected from 30 high schools randomly chosen from 237 regular full-time high schools registered in Shanghai. From each school, 40 students were selected from each of the tenth, eleventh and twelfth grades for a total of 120 students per school. The questionnaire involved questions pertaining to demographic profiles, learning environment and exercise habits of each student. And it also contained questions regarding the amount of weight carried by each student while commuting to and from school, and it was also used to collect specific information related to the occurrence of NSP and LBP. Logistic regression was performed to analyze the potential risk factors for NSP and LBP. RESULTS: Among 3 600 questionnaires, a total of 2 842 valid ones were returned. The results revealed that the incidence of NSP and LBP in the Chinese adolescent population was 41.1% and 32.8% respectively. Both NSP and LBP were more common in girls than in boys, and 6.3% students reported at least one NSP- or LBP-induced absence from school. A relatively large portion of Chinese adolescents reported experiencing problems such as sedentary behavior (26.7% of the students continued to sit for more than 3 hours after school), a lack of exercise (29.3% exercised less than once each week and 38.2% of students reported that their exercise duration was less than half an hour each time) and overweight backpacks (53.0% complained that their backpack was too heavy). Multivariate logistic regression analysis revealed that gender, grade, physical activity and learning environment were all significantly correlated with the occurrences of NSP and LBP. CONCLUSION: The incidences of NSP and LBP are relatively high among adolescents in Shanghai. And several factors, including sedentary behavior, personal exercise habits and backpack weight, influence the occurrences of NSP and LBP in adolesents.

Orthodromic Reciprocating Tachycardia Relying on Aberrant Conduction: The Need for a Larger Circuit.

Aberrant conduction during orthodromic reciprocating tachycardia (ORT) prolongs the ventriculoatrial conduction time, which can be essential for the maintenance of tachycardia in specific cases. We searched for ORT relying on aberrancy among 220 cases in our center. Three patients showed the phenomenon of aberrancy-dependent ORT. All accessory pathways were located at the lateral regions of the atrioventricular annulus. None of them had a baseline bundle branch block (BBB). Creating a functional BBB was necessary to induce the tachycardias. In two cases, termination of tachycardias was directly associated with resolution of the aberration. In the other case, re-entry required both BBB and slow pathway conduction. We conclude that extra transseptal time caused by aberrancy can be an integral part of the ORT circuit, which explains the infrequent and unsustainable episodes of ORT in certain patients and is useful in understanding the circuit and localizing the pathway.

The surgical strategy "CSF decompression" facilitates outcomes of adults with Chiari malformation type I: An observational, real-world, single center study of 528 patients.

OBJECTIVES: We designed this study to introduce the surgical strategy "CSF decompression" in treating Chiari malformation type I (CMI), and compared the "CSF decompression" strategy with other surgical strategies to provide a solid basis for patient counseling. METHODS: A total of 528 consecutive CMI patients who underwent surgical interventions from 2012 to 2022 were enrolled. The surgical strategy for these patients was bony and dural decompression (BDD), anatomical reduction of herniated tonsils (AR) or CSF decompression (CSFD). Short-term results were determined after 3 months; long-term outcomes were evaluated at last follow-up and at least 18 months. RESULTS: The CSFD strategy was independently associated with better long- or short-term primary outcomes than AR or BDD (P < 0.001). Compared with short-term, the long-term outcomes were better in CSFD patients (P = 0.035), but were worse in BDD patients (P = 0.03). Specific surgical techniques cannot affect the long- and short-term outcomes of CMI patients. CSFD provided better long-term syringomyelia improvement than short-term (181/218, 83% vs 169/218, 77.5%; P < 0.001). CONCLUSION: The "CSF decompression" surgical strategy, but not a specific surgical technique or operative method, was associated with favorable neurological outcomes in adult CMI patients. The surgical technique and operative method should be selected according to the characteristics of each patient and the intraoperative condition to normalized CSF circulation at CVJ. The intraoperative target maybe smoothly CSF flow, out from the fourth ventricle and in to the bilateral Luschka foramina, could be observed.