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Gestational diabetes mellitus (GDM) is defined as the first onset of glucose intolerance in pregnancy without prior known diabetes. While it is commonly associated with metabolic risk factors such as obesity and hypertension, a small percentage of women with GDM have underlying autoimmune causes, with presence of islet-cell antibodies resulting in autoimmune-mediated destruction of the pancreas. We present a case of idiopathic postpartum pancreatitis precipitating fulminant diabetic ketoacidosis in a patient with otherwise well-controlled GDM during pregnancy, and subsequent findings of positive anti-glutamic acid decarboxylase antibody. This is the first presentation of autoimmune diabetes diagnosed postnatally in a woman who has no previous medical or family history.

To investigate preferences of pregnant women for the characteristics of prenatal testing, and to quantify their willingness-to-pay (WTP) for non-invasive prenatal testing (NIPT) as first-line screening for Down Syndrome.A cross-sectional discrete choice experiment survey including five testing attributes was administered to 192 pregnant women (≤14 weeks' gestation) who were aged ≥21 years in Singapore. We calculated marginal WTP for improvements in testing characteristics and NIPT.We identified two groups of women with distinct preferences for prenatal testing. Women aged ≥35 years, with at least a university education, and with intention to terminate pregnancy of an affected fetus were more likely to be in the group with higher WTP for improvements in test characteristics. While participants valued increased detection rate and lower screen positive rate associated with NIPT, they also valued no risk of test failure and ability to test for birth defects using standard testing. The participants, on average, were not willing to pay for NIPT over the standard testing as a first-line screening test.As a first-line screening, NIPT was not preferred over standard testing. The prenatal consultations should focus on each testing characteristic equally as our findings show diverse preferences for testing characteristics.

The study aimed to investigate whether serum sFlt-1 (soluble fms-like tyrosine kinase-1) at 11-13 weeks’ gestation in pregnancies that subsequently developed preeclampsia was different from those without preeclampsia and compare screening performance of the International Prediction of Pregnancy Complications (IPPIC) reported models, which include various combinations of maternal factors, systolic blood pressure, diastolic blood pressure, PlGF (placental growth factor) and sFlt-1 and the competing risk (CR) models, which include various combinations of maternal factors, mean arterial pressure (MAP) and PlGF for predicting any-onset, early-onset, and late-onset preeclampsia. This was a prospective multicenter study in 7877 singleton pregnancies. The differences of the predictive performance between the IPPIC and CR models were compared. There were 141 women (1.79%) who developed preeclampsia, including 13 cases (0.17%) of early-onset preeclampsia and 128 cases (1.62%) of late-onset preeclampsia. In pregnancies that developed preeclampsia compared to unaffected pregnancies, median serum sFlt-1 levels and its MoMs were not significantly different ( p >0.05). There was no significant association between gestational age at delivery and log 10 sFlt-1 and log 10 sFlt-1 MoM ( p >0.05). The areas under the curve of CR models were significantly higher than the IPPIC models for the prediction of any-onset and late-onset preeclampsia but not for early-onset preeclampsia. In conclusion, there are no significant differences in the maternal serum sFlt-1 levels at 11-13 weeks’ gestation between women who subsequently develop preeclampsia and those who do not. Moreover, the CR models for the prediction of any-onset and late-onset preeclampsia perform better than the IPPIC reported model.

Objective The coronavirus disease 2019 (COVID-19) pandemic continues to present a major challenge to public health. Vaccine development requires an understanding of the kinetics of neutralizing antibody (NAb) responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods In total, 605 serum samples from 125 COVID-19 patients (from January 1 to March 14, 2020) varying in age, sex, severity of symptoms, and presence of underlying diseases were collected, and antibody titers were measured using a micro-neutralization assay with wild-type SARS-CoV-2. Results NAbs were detectable approximately 10 days post-onset (dpo) of symptoms and peaked at approximately 20 dpo. The NAb levels were slightly higher in young males and severe cases, while no significant difference was observed for the other classifications. In follow-up cases, the NAb titer had increased or stabilized in 18 cases, whereas it had decreased in 26 cases, and in one case NAbs were undetectable at the end of our observation. Although a decreasing trend in NAb titer was observed in many cases, the NAb level was generally still protective. Conclusion We demonstrated that NAb levels vary among all categories of COVID-19 patients. Long-term studies are needed to determine the longevity and protective efficiency of NAbs induced by SARS-CoV-2.

Proteomic tools were used to identify the key proteins that might be associated with bronchial asthma(BA). Firstly, the serum samples from healthy adults and asthmatic patients were collected. Tandem Mass Tag~(TM)(TMT), which removes high-abundance structures and nonspecific proteins, was employed to identify the differentially expressed proteins between asthmatic patients and healthy adults. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were carried out for the differentially expressed proteins. The core proteins in the asthma group were screened out by protein-protein interaction(PPI) analysis. Then the core proteins were verified by Western blot for 3 patients with bronchial asthma and 3 healthy adults. A total of 778 differentially expressed proteins were screened out, among which 32 proteins contained quantitative information, including 18 up-regulated proteins and 14 down-regulated proteins. The differentially expressed proteins were enriched in 28 KEGG signaling pathways. The PPI analysis showed that 10 proteins(GDN, 1433 Z, VWF, HEMO, CERU, A1 AT, TSP1, G3 P, IBP7, and KPYM) might be involved in the pathogenesis of bronchial asthma. Compared with those in healthy adults, the expression levels of SLC25 A4, SVEP1, and KRT25 in the sera of asthmatic patients were up-regulated(Plt;0.05). Therefore, it is hypothesized that a variety of immune signaling pathways and differentially expressed proteins play a role in the pathogenesis of BA, which provides potential target information for the treatment of BA.

Purpose To evaluate the contralateral lymph node recurrence rate (clLNRR) of stage IVA to IVB well-lateralized oral cavity cancer. To evaluate the risk factors of clLNRR. Materials and methods Pathologic stage IVA-B squamous cell carcinoma of oral cavity, originating from buccal mucosa, gingiva, or retromolar trigone were retrospectively recruited. Those who did not receive definitive surgery, with previous cancer history, or with contralateral nodal metastasis at diagnosis were excluded. Results From 2010 to 2017, 120 cases were enrolled, including 103 pT4 and 38 pN2. Thirty-one patients underwent contralateral neck dissection, and 18 had contralateral elective nodal irradiation. After median follow up of 35.1 months, the 3-year clLNRR was 15.7% (95% CI: 8.8 - 22.6%) as first event and was 17.1% (95% CI: 9.8 - 24.4%) for overall recurrences. The 3-year disease-free survival and overall survival were 52.8% and 63.1%, respectively. In multivariate analysis, positive nodal metastasis, gingival origin, and perineural invasion were associated with significantly higher clLNRR. Nodal metastasis was the strongest prognostic factor for clLNRR (pN1, HR: 17.1, p = 0.010; pN2, HR: 16.7, p = 0.004, comparing to pN0). The 3-year clLNRR were 2.9% for pN0 (n = 71, 95% CI: 0 - 6.8%), 37.7% for pN1 (n = 11, 95% CI: 8.3 - 67.1%), and 38.4% for pN2 (n = 38, 95% CI: 19.2 - 57.6%). Advanced T classification, elective contralateral neck dissection, and contralateral nodal irradiation did not have significant impact on clLNRR. Conclusions Positive homolateral nodal metastasis, gingival origin, and perineural invasion were risk factors correlated with significantly higher clLNRR. For patient without nodal metastasis, the clLNRR was low and elective contralateral neck management might be safely omitted. For patients with homolateral nodal disease, the contralateral nodal recurrence was not unusual. The optimal treatment for these high risk patients warrant further research.

Background Robot-assisted gait training (RAGT) is a practical treatment that can complement conventional rehabilitation by providing high-intensity repetitive training for patients with stroke. RAGT systems are usually either of the end-effector or exoskeleton types. We developed a novel hybrid RAGT system that leverages the advantages of both types. Objective This single-blind randomized controlled trial evaluated the beneficial effects of the novel RAGT system both immediately after the intervention and at the 3-month follow-up in nonambulatory patients with subacute stroke. Methods We recruited 40 patients with subacute stroke who were equally randomized to receive conventional rehabilitation either alone or with the addition of 15 RAGT sessions. We assessed lower-extremity motor function, balance, and gait performance by using the following tools: active range of motion (AROM), manual muscle test (MMT), the Fugl–Meyer Assessment (FMA) lower-extremity subscale (FMA-LE) and total (FMA-total), Postural Assessment Scale for Stroke (PASS), Berg Balance Scale (BBS), Tinetti Performance-Oriented Mobility Assessment (POMA) balance and gait subscores, and the 3-m and 6-m walking speed and Timed Up and Go (TUG) tests. These measurements were performed before and after the intervention and at the 3-month follow-up. Results Both groups demonstrated significant within-group changes in the AROM, MMT, FMA-LE, FMA-total, PASS, BBS, POMA, TUG, and 3-m and 6-m walking speed tests before and after intervention and at the 3-month follow-up (p p = 0.014) and total (p = 0.002) assessments. Conclusion Although the novel hybrid RAGT is effective, strong evidence supporting its clinical effectiveness relative to controls in those with substantial leg dysfunction after stroke remains elusive. Trial registration The study was registered with an International Standard Randomized Controlled Trial Number, ISRCTN, ISRCTN15088682. Registered retrospectively on September 16, 2016, at https://www.isrctn.com/ISRCTN15088682

The novel coronavirus disease (COVID-19) pandemic remains a global public health crisis, presenting a broad range of challenges. To help address some of the main problems, the scientific community has designed vaccines, diagnostic tools and therapeutics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The rapid pace of technology development, especially with regard to vaccines, represents a stunning and historic scientific achievement. Nevertheless, many challenges remain to be overcome, such as improving vaccine and drug treatment efficacies for emergent mutant strains of SARS-CoV-2. Outbreaks of more infectious variants continue to diminish the utility of available vaccines and drugs. Thus, the effectiveness of vaccines and drugs against the most current variants is a primary consideration in the continual analyses of clinical data that supports updated regulatory decisions. The first two vaccines granted Emergency Use Authorizations (EUAs), BNT162b2 and mRNA-1273, still show more than 60% protection efficacy against the most widespread current SARS-CoV-2 variant, Omicron. This variant carries more than 30 mutations in the spike protein, which has largely abrogated the neutralizing effects of therapeutic antibodies. Fortunately, some neutralizing antibodies and antiviral COVID-19 drugs treatments have shown continued clinical benefits. In this review, we provide a framework for understanding the ongoing development efforts for different types of vaccines and therapeutics, including small molecule and antibody drugs. The ripple effects of newly emergent variants, including updates to vaccines and drug repurposing efforts, are summarized. In addition, we summarize the clinical trials supporting the development and distribution of vaccines, small molecule drugs, and therapeutic antibodies with broad-spectrum activity against SARS-CoV-2 strains.

To compare the treatment outcome and severe late adverse effects (AEs) between conventional volume and dose (CVD) and simultaneously reduced volume and dose (SRVD) of clinical target volume treatments in patients with nasopharyngeal carcinoma.This retrospective cohort study enrolled patients with nonmetastatic stage II to IV nasopharyngeal cancer from a single institute. Survival endpoints and severe (≥grade 3) late AEs and comorbidity were compared between groups. The correlation of severe late AEs, comorbidity, and overall survival (OS) were evaluated using Kaplan-Meier and Cox regression methods.From January 2012 to June 2017, this study enrolled 178 patients, 64 in the CVD group and 114 in the SRVD group. The 2 groups did not differ significantly in patient characteristics except for mean follow-up time (37.6 vs 48.8 months; P = .01). The SRVD group did not significantly differ from the CVD group in local control survival (82.0% vs 78.4%; P = .85), regional control survival (89.9% vs 86.0%; P = .62), or disease-free survival (76.4% vs 66.9%; P = .67). The SRVD group had significantly better OS (93.9% vs 67.0%; P.001) and salvage survival (79.3% vs 20.7%; P.01) and a significantly lower ratio of severe lung infection (1 of 113 vs 5 of 59; P = .02). The SRVD group had a significantly lower risk of mortality (hazard ratio [HR], 0.3; P = .03). The factors associated with a significantly higher risk of mortality were N3 (regional lymph node stage status of N3) (HR, 3.0; P = .02); comorbidities of diabetes, coronary artery disease, or chronic kidney disease (grades 2-3) (HR, 3.8; P = .009), and severe lung infection (HR, 6.3; P = .007).Simultaneously reduced volume and dose of clinical target volumes did not impair locoregional control or disease-free survival. The benefits of SRVD treatment may include significant reduction in severe late AEs, particularly lung infection, dysphagia, and xerostomia. However, additional studies with longer patient follow-up are required to confirm these benefits.

Background To assess the benefit of postoperative radiotherapy in patients with pT1-2N1M0 oral and oropharyngeal cancer by the quality of neck dissection. Methods In the Surveillance, Epidemiology, and End Results database, pT1-2N1M0 oral and oropharyngeal cancer patients treated by primary tumor resection and neck dissection with or without radiotherapy were included between 2004 and 2015. Univariate and multivariate analysis were used to explore the effect of adjuvant radiotherapy on 5-year overall survival (OS) and disease-specific survival (DSS) among different quality of neck dissection. Results Of the 1765 patients identified, 1108 (62.8%) had oral cancer, 1141 (64.6%) were men, and 1067 (60.5%) underwent adjuvant radiotherapy. After adjusting for confounding factors, postoperative radiotherapy reduced the adjusted hazard ratio (aHR) of 5-year OS to 0.64 (95% confidence interval [CI] 0.49–0.84) in those with Conclusion Radiotherapy was associated with improved survival in pT1-2N1M0 oral and oropharyngeal cancer patients without adequate neck dissection.

Context The traditional drying method, sun drying, for Chrysanthemum morifolium Ramat. cv. Hang-ju (Compositae) (HJ) is widely replaced by sulphur fumigation (SF), which has an unknown effect on its efficacy. Objective To investigate protective effects of nonfumigated HJ (NHJ) and sulphur-fumigated HJ (SHJ) water extracts against oxidative stress and lipid peroxidation. Materials and methods Sprague-Dawley rats were administered high-fat diet to induce hyperlipidaemia and randomly divided into eight groups (n = 6): control, fenofibrate, NHJ and SHJ extracts (1, 2 or 4 g crude drugs/kg/d; intragastric administration for 8 weeks). Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected. Human umbilical vein endothelial cells (HUVECs) were treated with NHJ and SHJ extracts (50, 100 or 200 μg/mL) for 24 h, followed by oxidized low-density lipoprotein (ox-LDL, 20 μg/mL) for 2 h in vitro. Cellular reactive oxygen species (ROS), SOD and MDA levels and apoptosis were evaluated. Results NHJ was more effective than SHJ in decreasing serum TG, TC, LDL-C, LDL/HDL and MDA while increasing serum HDL-C and SOD levels at high doses. SHJ (IC50=19.9 mg/mL) suppressed HUVEC growth stronger than NHJ (IC50=186.7 mg/mL). At 200 μg/mL, NHJ was more effective than SHJ in downregulating ROS and MDA levels, reducing HUVECs apoptosis rate and elevating SOD activity in ox-LDL-treated HUVECs. Conclusions SF causes oxidative damage and attenuates antioxidative activity in ox-LDL-treated HUVECs, which promotes lipid peroxidation. SF is not recommended for processing HJ.

We report the synthesis and evaluation of a series of cell-permeable and N- versus O-selective sialyltransferase inhibitors. Inhibitor design entailed the functionalization of lithocholic acid at C(3) and at the cyclopentane ring side chain. Among the series, FCW34 and FCW66 were shown to inhibit MDA-MB-231 cell migration as effectively as ST3GALIII-gene knockdown did. FCW34 was shown to inhibit tumor growth, reduce angiogenesis, and delay cancer cell metastasis in animal models. Furthermore, FCW34 inhibited vessel development and suppressed angiogenic activity in transgenic zebrafish models. Our results provide clear evidence that FCW34-induced sialyltransferase inhibition reduces cancer cell metastasis by decreasing N-glycan sialylation, thus altering the regulation of talin/integrin/FAK/paxillin and integrin/NFκB signaling pathways.

Glioma is a primary, malignant, and aggressive brain tumor in adults. To develop new therapeutic strategies for glioma, we must determine its underlying mechanisms. In the present study, we aimed to investigate the potential role of miR-1272-ADAM9-CDCP1 signaling in the progression of glioma. We found that ectopic expression of miR-1272 produced significant inhibitory effects on cell proliferation and migration and was associated with cell cycle G0/G1 arrest in A172 and SHG44 glioma cells. Using the luciferase reporter assay, we identified ADAM9 as a target of miR-1272. The expression of ADAM9 was markedly decreased or increased after overexpression or inhibition, respectively, of miR-1272 in glioma cells. Moreover, overexpression of ADAM9 reversed the inhibitory effects of miR-1272 on glioma cell progression. Furthermore, CDCP1 served as a potential downstream molecule of miR-1272/ADAM9 signaling in glioma and promoted the proliferation and migration of glioma. Results derived from clinical samples and online databases confirmed correlations between the expression of ADAM9 and CDCP1 and both the severity and prognosis of glioma. In conclusion, these results suggest that miR-1272 and CDCP1 may act as novel regulators in glioma. The miR-1272/ADAM9/CDCP1 pathway may serve as a potential candidate pathway for the prevention of glioma.

Background The smart hospital's concept of using the Internet of Things (IoT) to reduce human resources demand has become more popular in the aging society. Objective To implement the voice smart care (VSC) system in hospital wards and explore patient acceptance via the Technology Acceptance Model (TAM). Methods A structured questionnaire based on TAM was developed and validated as a research tool. Only the patients hospitalized in the VSC wards and who used it for more than two days were invited to fill the questionnaire. Statistical variables were analyzed using SPSS version 24.0. A total of 30 valid questionnaires were finally obtained after excluding two incomplete questionnaires. Cronbach’s α values for all study constructs were above 0.84. Result We observed that perceived ease of use on perceived usefulness, perceived usefulness on user satisfaction and attitude toward using, and attitude toward using on behavioral intention to use had statistical significance (p Conclusion We have successfully developed the VSC system in a Taiwanese academic medical center. Our study indicated that perceived usefulness was a crucial factor, which means the system function should precisely meet the patients' demands. Additionally, a clever system design is important since perceived ease of use positively affects perceived usefulness. The insight generated from this study could be beneficial to hospitals when implementing similar systems to their wards.

The WHO declared the coronavirus disease 2019 (COVID-19) a global pandemic on 11 March 2020. Lessons from SARS epidemic led Singapore to develop stringent infection control protocols in preparation for future pandemics. However, unlike SARS, COVID-19 appears to be more transmissible and is predicted to continue for longer. As of 14 June 2020, there have been 40,197 positive cases with 26 deaths in Singapore, and KK Women’s and Children’s Hospital (KKH) has managed a total of 73 cases. Obstetrics ultrasound is an indispensable medical service and must continue to operate during a pandemic. A key balance must be struck between keeping patients and healthcare workers safe while being able to provide quality and prompt obstetric care. Our Antenatal Diagnostic Centre (ADC) in KKH developed new strategies to adapt to the pandemic when the national Disease Outbreak Response System Condition (DORSCON) was raised from yellow to orange on 7 February 2020. In this paper, we discuss our clinical workflow to reduce the risk of transmission amongst patients and staff while minimising disruption to our services.

Kawasaki disease (KD) is an acute febrile systemic vasculitis of unknown etiology that affects infants and young children. Considerable evidence supports the hypothesis that there is a genetic basis for KD susceptibility. Genome-wide association studies (GWAS) have identified several genetic variants associated with KD. This study aims to replicate three novel KD-associated single nucleotide polymorphisms (SNPs), identified by GWAS in Japanese, in a Taiwanese population. Associations between these SNPs and development of coronary artery lesions (CALs) were also investigated. The rs2254546 A/G, rs2857151 A/G, and rs4813003 C/T SNPs were genotyped in 681 children with KD and 563 ethnically-matched healthy controls using TaqMan Assay or DNA sequencing. We found rs2254546 and rs4813003 SNPs were significantly associated with KD (G allele, odds ratio [OR] = 1.54, P = 1.0 × 10–5; C allele, OR = 1.32, P = 8.1 × 10–4). However, no evidence for associations with CAL development was observed. Our study successfully validates associations of the rs2254546 and rs4813003 SNPs with KD in a Taiwanese population. Further functional studies of the SNPs are important in understanding the pathogenesis of KD.

Human Leukocyte Antigen (HLA)-DQ2 and HLA-DQ8 are genetic risk factors for Type 1 Diabetes Mellitus (T1DM) and Celiac disease (CD) in Caucasians, but their association with Taiwanese Han population is unknown. We screened 532 Taiwanese T1DM patients for CD biomarkers including anti-tissue transglutaminase (TGM2), anti-gliadin and anti-neoepitope antibodies (Abs), sequencing DQB1 genotypes, and characterized the TGM2 Abs. We report that 3.76% of Taiwanese patients had TGM2-Abs and all had no CD's symptoms. In contrast to Caucasian's CD patients, DQ2/DQ8 only constituted ~4/5 of TGM2-Abs positive patients, while the other ~1/5 patients belonged to different HLA genotypes. Either anti-gliadin or anti-neoepitope Abs coexisted with ~3/4 of TGM2-Abs positive patients that were likely due to gluten-ingestion, while the cause of TGM2-Abs production for other ~1/4 of patients was unknown. Purified anti-TGM2 IgA (TGA) and anti-TGM2 IgG (TGG) could bind on endothelial cells surface, recognized native better than denatured forms of TGM2, and TGA inhibited TGM2's transamidation activity by up to 80% but TGG had no effects. Epitope mapping of all TGM2-Abs positive sera demonstrated that TGM2-Abs had heterogeneity in specificities. This is the first study on the differences between Taiwanese Han group and Caucasian in HLA genotypes and properties of TGM2-Abs.

Emerging and resurging mosquito-borne flaviviruses are an important public health challenge. The increased prevalence of dengue virus (DENV) infection has had a significant socioeconomic impact on epidemic countries. The recent outbreak of Zika virus (ZIKV) has created an international public health emergency because ZIKV infection has been linked to congenital defects and Guillain-Barre syndrome. To develop potentially prophylactic antiviral drugs for combating these acute infectious diseases, we have targeted the host calcium/calmodulin-dependent kinase II (CaMKII) for inhibition. By using CaMKII structure-guided inhibitor design, we generated four families of benzenesulfonamide (BSA) derivatives for SAR analysis. Among these substances, N-(4-cycloheptyl-4-oxobutyl)-4-methoxy-N-phenylbenzenesulfonamide (9) showed superior properties as a lead CaMKII inhibitor and antiviral agent. BSA 9 inhibited CaMKII activity with an IC50 value of 0.79 μM and displayed EC50 values of 1.52 μM and 1.91 μM against DENV and ZIKV infections of human neuronal BE(2)C cells, respectively. Notably, 9 significantly reduced the viremia level and increased animal survival time in mouse-challenge models.

Incorporation of water has been revealed to successfully facilitate visible-light photoredox catalysis of indole leading to increased production of C2-quaternary indolinone. The water-promoted photoreaction of indole under catalyst-free conditions by a household compact fluorescence light was also demonstrated. The antiproliferative activity of the synthesized indolinones was evaluated against three human cancer cell lines.

Background/Aim: Whole-body positron-emission tomography/computed tomography with the glucose analog 2-[(18)F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) has been used to screen examinees for underlying malignancy in many countries. The aim of this study was to compare the potential value of FDG-PET/CT application in asymptomatic individuals with those with suspected malignancy. Patients and Methods: A total of 9,408 examinees underwent whole-body FDG-PET/CT at our hospital from July 2006 to August 2013. Three thousand and seven hundred asymptomatic individuals and 848 individuals with laboratory and clinical/radiologicaI suspicion of malignancy who had undergone FDG-PET/CT for cancer screening were recruited. The final confirmation of cancer and outcomes were based on a pathological report and continuous follow-up. Results: Forty-five out of 3,700 asymptomatic individuals (1.2%) had proven malignancy, and 42 of them (93.3%) were found by FDG-PET/CT. Two hundred and twelve out of 848 with suspected malignancy (25%) had proven malignancy, and 196 of them (92.5%) were detected by FDG-PET/CT. Most of these cancers in asymptomatic individuals were clinically at an early stage. The discovery rate in asymptomatic individuals and those with suspected malignancy was 1.1% and 23.1%, respectively. The overall survival of patients with cancer diagnosed with PET/CT was higher than those with suspected malignancy (78.6% vs. 48.5%, p

SARS-CoV-2 wreaks havoc around the world, triggering the COVID-19 pandemic. It has been confirmed that the endoribonuclease NSP15 is crucial to the viral replication, and thus identified as a potential drug target against COVID-19. The NSP15 protein was used as the target to conduct high-throughput virtual screening on 30,926 natural products from the NPASS database to identify potential NSP15 inhibitors. And 100 ns molecular dynamics simulations were performed on the NSP15 and NSP15-NPC198199 system. In all, 10 natural products with high docking scores with NSP15 protein were obtained, among which compound NPC198199 scored the highest. The analysis of the binding mode between NPC198199 and NSP15 found that NPC198199 would form H-bond interactions with multiple key residues at the catalytic site. Subsequently, a series of post-dynamics simulation analyses (including RMSD, RMSF, PCA, DCCM, RIN, binding free energy, and H-bond occupancy) were performed to further explore inhibitory mechanism of compound NPC198199 on NSP15 protein at the molecular level. The research strongly indicates that the 10 natural compounds screened can be used as potential inhibitors of NSP15, and provides valuable information for the subsequent drug discovery of anti-SARS-CoV-2. PRACTICAL APPLICATIONS: Natural products play an important role in the treatment of many difficult diseases. In this study, high-throughput virtual screening technology was used to screen the natural product database to obtain potential inhibitors against endoribonuclease NSP15. The binding mechanism between natural products and NSP15 was investigated at the molecular level by molecular dynamics technology so that it is expected to become candidate drugs for the treatment of SARS-CoV-2. We hope that our research can provide new clue to combat COVID-19 and overcome the epidemic situation as soon as possible.

An overreliance on commercial, kit-based RNA extraction in the molecular diagnoses of infectious disease presents a challenge in the event of supply chain disruptions and can potentially hinder testing capacity in times of need. In this study, we adapted a well-established, robust TRIzol-based RNA extraction protocol into a high-throughput format through miniaturization and automation. The workflow was validated by RT-qPCR assay for SARS-CoV-2 detection to illustrate its scalability without interference to downstream diagnostic sensitivity and accuracy. This semi-automated, kit-free approach offers a versatile alternative to prevailing integrated solid-phase RNA extraction proprietary systems, with the added advantage of improved cost-effectiveness for high volume acquisition of quality RNA whether for use in clinical diagnoses or for diverse molecular applications.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been engendering enormous hazards to the world. We obtained the complete genome sequences of SARS-CoV-2 from imported cases admitted to the Guangzhou Eighth People's Hospital, which was appointed by the Guangdong provincial government to treat coronavirus disease 2019 (COVID-19). The SARS-CoV-2 diversity was analyzed, and the mutation characteristics, time, and regional trend of variant emergence were evaluated.In total, 177 throat swab samples were obtained from COVID-19 patients (from October 2020 to May 2021). High-throughput sequencing technology was used to detect the viral sequences of patients infected with SARS-CoV-2. Phylogenetic and molecular evolutionary analyses were used to evaluate the mutation characteristics and the time and regional trends of variants.We observed that the imported cases mainly occurred after January 2021, peaking in May 2021, with the highest proportion observed from cases originating from the United States. The main lineages were found in Europe, Africa, and North America, and B.1.1.7 and B.1.351 were the two major sublineages. Sublineage B.1.618 was the Asian lineage (Indian) found in this study, and B.1.1.228 was not included in the lineage list of the Pangolin web. A reasonably high homology was observed among all samples. The total frequency of mutations showed that the open reading frame 1a (ORF1a) protein had the highest mutation density at the nucleotide level, and the D614G mutation in the spike protein was the commonest at the amino acid level. Most importantly, we identified some amino acid mutations in positions S, ORF7b, and ORF9b, and they have neither been reported on the Global Initiative of Sharing All Influenza Data nor published in PubMed among all missense mutations.These results suggested the diversity of lineages and sublineages and the high homology at the amino acid level among imported cases infected with SARS-CoV-2 in Guangdong Province, China.

Young age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women.PubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest.We included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50-0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98-1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06-9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes.This study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.

Potent, cell-permeable, and subtype-selective sialyltransferase inhibitors represent an attractive family of substances that can potentially be used for the clinical treatment of cancer metastasis. These substances operate by specifically inhibiting sialyltransferase-mediated hypersialylation of cell surface glycoproteins or glycolipids, which then blocks the sialic acid recognition pathway and leads to deterioration of cell motility and invasion. A vast amount of evidence for the in vitro and in vivo effects of sialyltransferase inhibition or knockdown on tumor progression and tumor cell metastasis or colonization has been accumulated over the past decades. In this regard, this review comprehensively discusses the results of studies that have led to the recent discovery and development of sialyltransferase inhibitors, their potential biomedical applications in the treatment of cancer metastasis, and their current limitations and future opportunities.

To observe the effect ofThe patients with cerebral infarction were divided into an acupuncture group and a control group according to the random number table method, 27 cases in each group. In the control group, the basic treatment with conventional medication was used. In the acupuncture group, on the basic treatment as the control group, theCompared with their own pretreatment, the UE-FMA value was significantly higher after treatment in either of two groups separately (Tiaoren tongdu acupuncture significantly improves the upper limb movement function after cerebral infarction. The rFA value of PLIC combined with UE-FMA can be used to evaluate the therapeutic effect of acupuncture on the upper extremity movement after cerebral infarction.

To investigate the cytotoxic effect and its mechanism of the micromolecule compound on the leukemia cells.The cytotoxic effects of 28 Nilotinib derivatives on K562, KA, KG, HA and 32D cell lines were detected by MTT assays, and the compound Nilo 22 was screen out. Cell apoptosis and cell cycle on leukemia cells were detected by flow cytometry. The effect of compound screened out on leukemogenesis potential of MLL-AF9 leukemia mice GFPNilo 22 serves as the most outstanding candidate out of 28 Nilotinib derivatives, which impairs leukemia cell lines, but spares normal hematopoietic cell line. Comparing with Nilotinib, Nilo 22 could induce the apoptosis of GFPNilo 22 shows a significant cytotoxic effect on mice and human leukemia cells, especially for drug resistance cells. Nilo 22 is a promising anti-leukemia agent to solve the common clinical problems of drug resistance and relapse of leukemia.探究新型端粒酶抑制剂Nilo 22对白血病细胞的杀伤作用与机制.探讨一系列人工合成的小分子化合物对白血病细胞的杀伤作用及其作用机制.采用MTT法检测28个小分子化合物对K562、KA、KG、HA及32D细胞系的杀伤作用，筛选出安全有效的化合物Nilo 22。采用流式细胞术检测该化合物对MLL-AF9小鼠白血病细胞（GFP筛选到能有效杀伤白血病细胞系且对32D细胞系相对安全的小分子化合物Nilo 22；相对于尼洛替尼，Nilo 22诱导小鼠白血病细胞凋亡的作用更加显著，轻微地阻滞细胞周期于GNilo 22对白血病细胞有显著的杀伤作用，尤其对耐药细胞有很好的杀伤效果，有望成为治疗白血病的先导化合物以解决目前临床常见的白血病耐药和复发问题.

To develop a noninvasive model to predict significant fibrosis in children with chronic hepatitis B (CHB). A total of 116 CHB pediatric patients who underwent liver biopsy were included in the study. Liver histology, which is the gold standard for assessing fibrosis, was performed. Blood routine examination, coagulation function, liver biochemistry, viral serology, and viral load were analyzed. Receiver operating characteristic curve analysis was used to analyze the sensitivity and specificity of all possible cut-off values. Based on the correlation and difference analyses, 7 available clinical parameters (total bile acid, gamma-glutamyl transpeptidase [GGT], aspartate transaminase, direct bilirubin to total bilirubin ratio, alanine aminotransferase, prealbumin [PA], and cholinesterase) were included in the modeling analysis. A model to predict significant liver fibrosis was derived using the 2 best parameters (PA and GGT). The original model was Y=−1.803 ln PA(mg/L)+0.769lnGGT(U/L)+6.436. After the mathematical calculation, the G index=600 × GGT/PA2 predicted significant fibrosis, with an area under the receiving operating characteristics (AUROC) curve of 0.733, 95% confidence interval (0.643–0.811). The AUROC of the G index (0.733) was higher than that of aminotransferase to platelet ratio index (APRI) (0.680) and Fibrosis index based on 4 factors (FIB-4) (0.601) in predicting significant fibrosis in children with CHB. If the values of the G index were outside the range of 0.28 to 1.16, 52% of children with CHB could avoid liver biopsy, with an overall accuracy of 75%. The G index can predict and exclude significant fibrosis in children with CHB, and it may reduce the need for liver biopsy in children with CHB.

Fatty acids are derived from diet and fermentative processes by the intestinal flora. Two to five carbon chain fatty acids, termed short chain fatty acids (SCFA) are increasingly recognized to play a role in intestinal homeostasis. However, the characteristics of slightly longer 6 to 10 carbon, medium chain fatty acids (MCFA), derived primarily from diet, are less understood. Here, we demonstrated that SCFA and MCFA have divergent immunomodulatory propensities. SCFA down-attenuated host pro-inflammatory IL-1β, IL-6, and TNFα response predominantly through the TLR4 pathway, whereas MCFA augmented inflammation through TLR2. Butyric (C4) and decanoic (C10) acid displayed most potent modulatory effects within the SCFA and MCFA, respectively. Reduction in TRAF3, IRF3 and TRAF6 expression were observed with butyric acid. Decanoic acid induced up-regulation of GPR84 and PPARγ and altered HIF-1α/HIF-2α ratio. These variant immune characteristics of the fatty acids which differ by just several carbon atoms may be attributable to their origins, with SCFA being primarily endogenous and playing a physiological role, and MCFA exogenously from the diet.

SHP2 phosphatase, encoded by the PTPN11 gene, is a non-receptor PTP, which plays an important role in growth factor, cytokine, integrin, hormone signaling pathways, and regulates cellular responses, such as proliferation, differentiation, adhesion migration and apoptosis. Many studies have reported that upregulation of SHP2 expression is closely related to human cancer, such as breast cancer, liver cancer and gastric cancer. Hence, SHP2 has become a promising target for cancer immunotherapy. In this paper, we reported the identification of compound 1 as SHP2 inhibitor. Fragment-based ligand design, De novo design, ADMET and Molecular docking were performed to explore potential selective SHP2 allosteric inhibitors based on SHP836. The results of docking studies indicated that the selected compounds had higher selective SHP2 inhibition than existing inhibitors. Compound 1 was found to have a novel selectivity against SHP2 with an in vitro enzyme activity IC50 value of 9.97 μM. Fluorescence titration experiment confirmed that compound 1 directly bound to SHP2. Furthermore, the results of binding free energies demonstrated that electrostatic energy was the primary factor in elucidating the mechanism of SHP2 inhibition. Dynamic cross correlation studies also supported the results of docking and molecular dynamics simulation. This series of analyses provided important structural features for designing new selective SHP2 inhibitors as potential drugs and promising candidates for pre-clinical pharmacological investigations.

Background To date, there are just several studies comparing distal locked nails with distal unlocked nails in treating intertrochanteric fractures. We report the first meta-analysis about this issue. Methods Systematic search was conducted for studies in PubMed, Embase and Cochrane Library. Meta-analyses were performed regarding intra operative outcomes, complications and functional outcomes. Results Pooled results showed insignificant difference between distal locking group and distal unlocking group in hip pain (relative risk (RR) 1.14, 95% confidence interval (CI) 0.59-2.19), distal tip fracture (RR 1.08, 95% CI 0.37-3.11), lag screw cut-out (RR 1.60, 95% CI 0.54-4.78), delayed or nonunion (RR 1.32, 95% CI 0.25-7.06), deep vein thrombosis (RR 1.06, 95% CI 0.23-4.84), wound infection (RR 0.58, 95% CI 0.28-1.22), Harris hip score (standard mean deviation (SMD) 0.03, 95% CI -0.15 to 0.21) and walking ability. However, significant difference was detected in operation time (SMD 0.77, 95% CI 0.36-1.17), fluoroscopy exposure time (SMD 1.02, 95% CI 0.52-1.52), blood loss (SMD 0.80, 95% CI 0.62-0.99) and total incision length (SMD 1.16, 95% CI 0.86-1.47). Result of trial sequential analysis indicated conclusive evidence. Conclusion Current evidence indicates that the distal locked intramedullary nails should not be recommended as routine choice for stable intertrochanteric fractures.

Prompt and effective treatment of maternal depression during pregnancy is important as it is an independent predictor of negative maternal and fetal outcomes. Yoga is an increasingly popular non-pharmacological modality. This study thus aimed to undertake a meta-analysis of the efficacy of yoga-based interventions for maternal depression during pregnancy. A total of 8 clinical studies were systematically reviewed, and 6 studies with a total of 405 pregnant mothers were included in the final meta-analysis. Applying per-protocol analysis and a random-effects model, the pooled standardized mean difference (SMD) from baseline depressive score was −0.452 (95% CI: −0.816 to −0.880, P = 0.015), supporting a statistically significant beneficial effect of yoga-based interventions on mood. Overall, yoga-based interventions are a promising non-pharmacological option, however, most trials examined were preliminary, recruited only participants with mild depression, did not blind study participants and had relatively small sample sizes. Larger randomized, controlled trials should be encouraged.

Overexpressed EGFR and mutant K-Ras play vital roles in therapeutic resistance in colorectal cancer patients. To search for an effective therapeutic protocol is an urgent task. A secondary metabolite in the sponge Hippospongia sp., Heteronemin, has been shown to induce anti-proliferation in several types of cancers. A thyroxine-deaminated analogue, tetrac, binds to integrin αvβ3 to induce anti-proliferation in different cancers. Heteronemin- and in combination with tetrac-induced antiproliferative effects were evaluated. Tetrac enhanced heteronemin-induced anti-proliferation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC). Heteronemin and tetrac arrested cell cycle in different phases. Combined treatment increased the cell accumulation in sub-G1 and S phases. The combined treatment also induced the inactivation of EGFR signaling and downregulated the phosphorylated ERK1/2 protein in both cell lines. Heteronemin and the combination showed the downregulation of the phosphorylated and total PI3K protein in HT-29 cells (KRAS WT CRC). Results by NanoString technology and RT-qPCR revealed that heteronemin and combined treatment suppressed the expression of EGFR and downstream genes in HCT-116 cells (KRAS MT CRC). Heteronemin or combined treatment downregulated genes associated with cancer progression and decreased cell motility. Heteronemin or the combined treatment suppressed PD-L1 expression in both cancer cell lines. However, only tetrac and the combined treatment inhibited PD-L1 protein accumulation in HT-29 cells (KRAS WT CRC) and HCT-116 cells (KRAS MT CRC), respectively. In summary, heteronemin induced anti-proliferation in colorectal cancer cells by blocking the EGFR-dependent signal transduction pathway. The combined treatment further enhanced the anti-proliferative effect via PD-L1 suppression. It can be an alternative strategy to suppress mutant KRAS resistance for anti-EGFR therapy.

Background The development of telecommunication has strongly affected comprehensive scientific disciplines, including medical sciences. Objective This study aims to assess the patient satisfaction of the teleconsultation system used for the consultation of dermatological follow-up care. Methods The study was performed cross sectional patient satisfaction survey method conducted between February and April 2017 to determine patient satisfaction using MedX teleconsultation system. The patient sample of the current study was recruited from cosmetic laser clinic, Wanfang and Taipei Medical University hospital. The study was performed on 32 patient (n = 32) participants. All of them were at least university graduate. Consultants and patients were handled using the Android-based MedX mobile application, which is available through an application for Google Android cellular telephones. Its application consists of a demographic information, structured step-by-step questionnaire, essential medical information about each patient, and digital images of skin lesions. Results 28 patients completed the questionnaire. The mean ± SD age of the patients was 27.25 ± 4.039 years; 78.6% were women. The study shows that respondents have reported a high level (85.8%) of mean overall satisfaction for the teleconsultation service. The usability of the system has highest satisfaction rate of 90.5% among the other subscales especially in terms of data transfer and data displayed. Responses of the patient satisfaction questionnaire were analyzed by age and gender, no statistically significant difference between the variables was found. Conclusion Patients have shown high satisfaction with teleconsultation service and it is well accepted in the management of cosmetic dermatology service. In the future, MedX application can be integrated into other instant messaging applications such as Line, thus allowing doctors and patients to easily communicate with each other.

The number of migrant workers in Taiwan increases annually. The majority is from Indonesia and most of them are female caregivers. This study aims to determine the access to health services and the associated factors among Indonesian female domestic workers in Taiwan. In this cross-sectional study, data were collected from February to May 2019, using a structured questionnaire. Subsequently, multiple logistic regression was used to examine the association between socio-demographic factors and health service access. Two hundred and eighty-four domestic migrant workers were interviewed. Eighty-five percent of the respondents declared sickness at work, but only 48.8% seek health care services. Factors associated with health service access were marital status, income, and the availability of an attendant to accompany the migrant workers to the healthcare facilities. Language barrier and time flexibility were the main obstacles. Further research and an effective health service policy are needed for the domestic migrant workers to better access health care services.

Background Healthcare workers are usually the first responders during outbreaks and are instrumental in educating the populace about the prevention of different diseases and illnesses. The aim of this study was to assess the association between healthcare workers’ characteristics and knowledge, attitudes and practices toward Zika virus. Methods This was a cross-sectional study that collected data from healthcare workers at 3 medical facilities using a validated self-administered questionnaire between July 2017 – September 2017. Logistic regression models were used to examine the association between sociodemographic and knowledge, attitudes, and practices. Results A total of 190 healthcare workers were analyzed. Of these, 60, 72.6 and 64.7% had good knowledge, positive attitudes, and good practices toward Zika virus, respectively. Healthcare workers without a formal degree were less likely to have good knowledge of Zika virus (adjusted odds ratio (AOR) = 0:49; 95% confidence interval (CI) = 0.24–0.99) compared to those with a formal degree. Reduced odds for positive attitude towards Zika virus were observed in healthcare workers with low income as compared to those with high income (AOR = 0.31; 95% CI =0.13–0.75). Being younger than 40 years old was associated with poor Zika virus practices (AOR = 0:34; 95% CI = 0.15–0.79). Conclusions Significant association between healthcare workers’ sociodemographic characteristics and Zika virus knowledge, attitudes and practices were observed. Public health interventions that seek to increase Zika virus awareness should aim to train healthcare workers who are younger, without formal degree and those earning low income.

Enzyme engineering is an indispensable tool in the field of synthetic biology, where enzymes are challenged to carry out novel or improved functions. Achieving these goals sometimes goes beyond modifying the primary sequence of the enzyme itself. The use of protein or nucleic acid scaffolds to enhance enzyme properties has been reported for applications such as microbial production of chemicals, biosensor development and bioremediation. Key advantages of using these assemblies include optimizing reaction conditions, improving metabolic flux and increasing enzyme stability. This review summarizes recent trends in utilizing genetically encodable scaffolds, developed in line with synthetic biology methodologies, to complement the purposeful deployment of enzymes. Current molecular tools for constructing these synthetic enzyme-scaffold systems are also highlighted.

Background High quality lymph node (LN) yield could increase survival, however strategies to improve LN yield have been seldom reported. This study aimed to assess the multiple-step action to promote quality of neck dissection in oral cancer. Methods A total of 400 patients with oral cancer who underwent primary tumor resection and neck dissection, including elective and radical neck dissection, were recruited after propensity score matching by clinical T and N categories between January 2009 and September 2018. Patients were treated by two independent departments in our institute. A multiple-step action was initiated in October 2015 in one department, and another department was as a control group. The impact of multiple-step action on LN yield and regional recurrence were analyzed using multivariate analysis and difference-in-differences (DID) linear regression analysis. Results The mean patient age was 55.2 + 11.1 years, and 92% were male. A total of 180 (45%) patients had T3-4 disease, and 129 (32%) patients had N2-3 disease. The multivariate linear regression and DID analyses revealed that multiple-step action had a positive effect on LN yield. A net improvement of LN yield with a coefficient of 13.78 (p p = 0.072) through DID analysis was noted. Conclusions Multiple-step action was associated with increased LN yield and decreased regional recurrence in patients with oral cancer. The observed activity may promote surgeons to improve the quality of neck dissections, is feasible, and could be applied to a widespread patient population.

Alcohol-associated liver disease (ALD) is a liver system disease caused by alcohol abuse, and it involves complex processes ranging from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. Steatosis and inflammation are the main phenomena involved in ALD. Ubiquitin-specific protease 22 (USP22) plays an important role in liver steatosis; however, its functional contribution to ALD remains unclear. USP22-silenced mice were fed a Lieber-DeCarli liquid diet. AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4. Here, we report that hepatic USP22 expression was dramatically upregulated in mice with ALD. Inflammation and steatosis were significantly ameliorated following USP22 silencing in vivo, as indicated by decreased IL-6 and IL-1β levels. We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells. Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions. More importantly, the expression levels of USP22 and BRD4 in patients with ALD were significantly increased. In conclusion, USP22 acts a key pathogenic factor in ALD by deubiquitinating BRD4, which facilitates the inflammatory response and aggravates ALD.

Background The collection and analysis of alert logs are necessary for hospital administrators to understand the types and distribution of alert categories within the organization and reduce alert fatigue. However, this is not readily available in most homegrown Computerized Physician Order Entry (CPOE) systems. Objective To present a novel method that can collect alert information from a homegrown CPOE system (at an academic medical center in Taiwan) and conduct a comprehensive analysis of the number of alerts triggered and alert characteristics. Methods An alert log collector was developed using the Golang programming language and was implemented to collect all triggered interruptive alerts from a homegrown CPOE system of a 726-bed academic medical center from November 2017 to June 2018. Two physicians categorized the alerts from the log collector as either clinical or non-clinical (administrative). Results Overall, 1,625,341 interruptive alerts were collected and classified into 1,474 different categories based on message content. The sum of the top 20, 50, and 100 categories of most frequently triggered alerts accounted for approximately 80, 90 and 97 percent of the total triggered alerts, respectively. Among alerts from the 100 most frequently triggered categories, 1,266,818 (80.2%) were administrative and 312,593 (19.8%) were clinical alerts. Conclusion We have successfully developed an alert log collector that can serve as an extended function to retrieve alerts from a homegrown CPOE system. The insight generated from the present study could also potentially bring value to hospital system designers and hospital administrators when redesigning their CPOE system.

Intervertebral disc degeneration (IVDD) is a common cause of low back pain. This study is aimed at investigating the role of microRNAs (miRNAs) in regulating human nucleus pulposus (NP) cell injury induced by tumor necrosis factor- (TNF-) α in IVDD. In this study, we induced NP cells with 20 ng/mL TNF-α in vitro, which promoted the obvious apoptosis of NP cells and the activation of nuclear transcription factor (NF)-κB. In contrast, using the specific NF-κB inhibitor BAY 11-7082 to treat cells greatly impaired the activation of NF-κB and increased the sensitivity of NP cells to TNF-α-induced apoptosis. Moreover, both TNF-α and BAY 11-7082 treatments were associated with marked miRNA dysregulation, with miR-502 being upregulated by TNF-α treatment and downregulated by BAY 11-7082 treatment, respectively. And the overexpression of miR-502 enhanced NF-κB activation and suppressed apoptosis of human NP cells induced by TNF-α, whereas the opposite was observed following miR-502 inhibition. Last, through bioinformatic analyses and luciferase reporter gene experiments, we identified TRAF2, an important activator of NF-κB, as a miR-502 target gene. Similarly, siRNA-mediated knockdown of the TRAF2 expression also suppressed TNF-α-induced apoptosis and enhanced NF-κB activation. Our findings provide evidence indicating that miR-502 is a key regulator of apoptosis of human NP cells induced by TNF-α by targeting TRAF2 and activating NF-κB.

The current COVID-19 pandemic is probably the worst the world has ever faced since the start of the new millennium. Although the respiratory system is the most prominent target of SARS-CoV-2 (the contagion of COVID-19), extrapulmonary involvement are emerging as important contributors of its morbidity and lethality. This article summarizes the impact of SARS-CoV and SARS-CoV-2 on the endocrine system to facilitate our understanding of the nature of coronavirus-associated endocrinopathy. Although new data are rapidly accumulating on this novel infection, many of the endocrine manifestations of COVID-19 remain incompletely elucidated. We, hereby, summarize various endocrine dysfunctions including coronavirus-induced new onset diabetes mellitus, hypocortisolism, thyroid hormone, and reproductive system aberrations so that clinicians armed with such insights can potentially benefit patients with COVID-19 at the bedside.

It has been confirmed that the new coronavirus SARS-CoV-2 caused the global pandemic of coronavirus disease 2019 (COVID-19). Studies have found that 3-chymotrypsin-like protease (3CLpro) is an essential enzyme for virus replication, and could be used as a potential target to inhibit SARS-CoV-2. In this work, 3CLpro was used as the target to complete the high-throughput virtual screening of the FDA-approved drugs, and Indinavir and other 10 drugs with high docking scores for 3CLpro were obtained. Studies on the binding pattern of 3CLpro and Indinavir found that Indinavir could form the stable hydrogen bond (H-bond) interactions with the catalytic dyad residues His41-Cys145. Binding free energy study found that Indinavir had high binding affinity with 3CLpro. Subsequently, molecular dynamics simulations were performed on the 3CLpro and 3CLpro-Indinavir systems, respectively. The post-dynamic analyses showed that the conformational state of the 3CLpro-Indinavir system transformed significantly and the system tended to be more stable. Moreover, analyses of the residue interaction network (RIN) and H-bond occupancy revealed that the residue-residue interaction at the catalytic site of 3CLpro was significantly enhanced after binding with Indinavir, which in turn inactivated the protein. In short, through this research, we hope to provide more valuable clues against COVID-19.

The most common cancer, lung cancer, causes deaths worldwide. Most lung cancer patients have non-small cell lung carcinomas (NSCLCs) with a poor prognosis. The chemotherapies frequently cause resistance therefore search for new effective drugs for NSCLC patients is an urgent and essential issue. Deaminated thyroxine, tetraiodothyroacetic acid (tetrac), and its nano-analogue (NDAT) exhibit antiproliferative properties in several types of cancers. On the other hand, the most abundant secondary metabolite in the sponge Hippospongia sp., heteronemin, shows effective cytotoxic activity against different types of cancer cells. In the current study, we investigated the anticancer effects of heteronemin against two NSCLC cell lines, A549 and H1299 cells in vitro. Combined treatment with heteronemin and tetrac derivatives synergistically inhibited cancer cell growth and significantly modulated the ERK1/2 and STAT3 pathways in A549 cells but only ERK1/2 in H1299 cells. The combination treatments induce apoptosis via the caspases pathway in A549 cells but promote cell cycle arrest via CCND1 and PCNA inhibition in H1299 cells. In summary, these results suggest that combined treatment with heteronemin and tetrac derivatives could suppress signal transduction pathways essential for NSCLC cell growth. The synergetic effects can be used potentially as a therapeutic procedure for NSCLC patients.

Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC) patients. This study aims to determine whether combining radiotherapy with sorafenib administration increases its efficacy. The study cohort included 4763 patients with diagnosed advanced HCC who received sorafenib between January 2012 and December 2015, as reported in medical records in the Taiwan Cancer Registry database. The effect of sorafenib with or without radiotherapy on survival was calculated using the Kaplan–Meier method and compared using the log-rank test. A Cox proportional hazards model was used for multivariate analysis. Patients receiving sorafenib plus radiotherapy had greater 1-year survival than did those receiving sorafenib alone (P

Intestinal myiasis caused by fly larvae parasitic in gastrointestinal tract was rare reported in children. We reported an infant with bloody diarrhea caused by intestinal myiasis. A 1 year and 7 months old boy presented with the only symptom of bloody diarrhea of unknown origin. In the second week of onset, numerous moving worms were observed in the bloody stool after bowel preparation with polyethylene glycol for colonoscopy. The bloody diarrhea disappeared after 1 week of combined therapy with albendazole and metronidazole. On follow-up after 6 months, the patient remained well without bloody diarrhea. In conclusion, intestinal myiasis being a rare disease that is very challenging to diagnose, physicians should remember it when they receive cases of bloody diarrhea with non-specific symptoms without any apparent cause.

Chinese hamster ovary (CHO) cells are the superior host cell culture models used for the bioproduction of therapeutic proteins. One of the prerequisites for bioproduction using CHO cell lines is the need to generate stable CHO cell lines with optimal expression output. Antibiotic selection is commonly employed to isolate and select CHO cell lines with stable expression, despite its potential negative impact on cellular metabolism and expression level. Herein, we present a novel proline-based selection system for the isolation of stable CHO cell lines. The system exploits a dysfunctional proline metabolism pathway in CHO cells by using a pyrroline-5-carboxylate synthase gene as a selection marker, enabling selection to be made using proline-free media. The selection system was demonstrated by expressing green fluorescent protein (GFP) and a monoclonal antibody. When GFP was expressed, more than 90% of stable transfectants were enriched within 2 weeks of the selection period. When a monoclonal antibody was expressed, we achieved comparable titers (3.35 ± 0.47 μg/mL) with G418 and Zeocin-based selections (1.65 ± 0.46 and 2.25 ± 0.07 μg/mL, respectively). We further developed a proline-based coselection by using S. cerevisiae PRO1 and PRO2 genes as markers, which enables the generation of 99.5% double-transgenic cells. The proline-based selection expands available selection tools and provides an alternative to antibiotic-based selections in CHO cell line development.

Diffuse pigmented villonodular synovitis (PVNS) of knee is a rare benign disease that has a destructive clinical course. Synovectomy and adjuvant radiotherapy (RT) have been reported as treatment options but literatures reporting functional outcomes were sparse. This study aimed to evaluate the long-term functional outcomes and disease control among treatment modalities through the 22 years of experience.A single-center database was searched for patients who received synovectomy of knee with the pathologic diagnosis of PVNS. General data, treatment modalities, and recurrent status were retrospectively collected from medical records. Functional outcomes were evaluated by Western Ontario and McMaster Universities Osteoarthritis Index through phone interviews by an independent orthopedist.From January 1995 to December 2017, 24 patients with diffuse PVNS of knee were identified, including 19 receiving open synovectomy (OP) and 5 undergoing arthroscopic surgery. Adjuvant RT was performed on 14 patients with a median dose of 35 Gy (range 20-40 Gy). After median follow up of 6 years, recurrences were recorded in 10 cases. The recurrence rate was significantly lower in the OP + RT group than the OP group (8.3% vs 57.1%, P = .038). Among those with preserved knee joints, there was no significant difference in the Western Ontario and McMaster Universities Osteoarthritis Index score and stiffness score between patients in the OP + RT and OP groups.For patients with diffuse PVNS of knee, the addition of moderate-dose adjuvant RT following OP provided excellent local control while maintaining good joint function with limited treatment-related morbidity. Our study emphasized the importance of moderate dose RT in diffuse PVNS of knee joint.