Added value of arterial enhancement fraction derived from dual-energy computed tomography for preoperative diagnosis of cervical lymph node metastasis in papillary thyroid cancer: initial results.

OBJECTIVES: To explore the added value of arterial enhancement fraction (AEF) derived from dual-energy computed tomography CT (DECT) to conventional image features for diagnosing cervical lymph node (LN) metastasis in papillary thyroid cancer (PTC). METHODS: A total of 273 cervical LNs (153 non-metastatic and 120 metastatic) were recruited from 92 patients with PTC. Qualitative image features of LNs were assessed. Both single-energy CT (SECT)-derived AEF (AEFS) and DECT-derived AEF (AEFD) were calculated. Correlation between AEFD and AEFS was determined using Pearson's correlation coefficient. Multivariate logistic regression analysis with the forward variable selection method was used to build three models (conventional features, conventional features + AEFS, and conventional features + AEFD). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. RESULTS: Abnormal enhancement, calcification, and cystic change were chosen to build model 1 and the model provided moderate diagnostic performance with an area under the ROC curve (AUC) of 0.675. Metastatic LNs demonstrated both significantly higher AEFD (1.14 vs 0.48; p < 0.001) and AEFS (1.08 vs 0.38; p < 0.001) than non-metastatic LNs. AEFD correlated well with AEFS (r = 0.802; p < 0.001), and exhibited comparable performance with AEFS (AUC, 0.867 vs 0.852; p = 0.628). Combining CT image features with AEFS (model 2) and AEFD (model 3) could significantly improve diagnostic performances (AUC, 0.865 vs 0.675; AUC, 0.883 vs 0.675; both p < 0.001). CONCLUSIONS: AEFD correlated well with AEFS, and exhibited comparable performance with AEFS. Integrating qualitative CT image features with both AEFS and AEFD could further improve the ability in diagnosing cervical LN metastasis in PTC. CLINICAL RELEVANCE STATEMENT: Arterial enhancement fraction (AEF) values, especially AEF derived from dual-energy computed tomography, can help to diagnose cervical lymph node metastasis in patients with papillary thyroid cancer, and complement conventional CT image features for improved clinical decision making. KEY POINTS: • Metastatic cervical lymph nodes (LNs) demonstrated significantly higher arterial enhancement fraction (AEF) derived from dual-energy computed tomography (DECT) and single-energy CT (SECT)-derived AEF (AEFS) than non-metastatic LNs in patients with papillary thyroid cancer. • DECT-derived AEF (AEFD) correlated significantly with AEFS, and exhibited comparable performance with AEFS. • Integrating qualitative CT images features with both AEFS and AEFD could further improve the differential ability.

Molybdenum-catalyzed deoxygenative heterocyclization of 2-nitroazobenzenes: a novel strategy for catalytic synthesis of 2-aryl-2H-benzo[d][1,2,3]triazoles.

A novel strategy for the catalytic synthesis of 2-aryl-2H-benzo[d][1,2,3]triazoles bearing a wide range of functional groups in good to excellent yields by non-noble molybdenum-catalyzed deoxygenative heterocyclization of 2-nitroazobenzenes is described. The salient features of the transformation include the use of readily available substrates, valuable products and ease of scale-up. The mechanistic study indicates that the reaction occurred via double deoxygenation by the Mo(VI)/Mo(IV) catalytic cycle from 2-nitroazobenzene, through the formation of 2-aryl-2H-benzo[d][1,2,3]triazole-N1-oxide or nitrene intermediates.

Low-Intensity Extracorporeal Shock Wave Therapy Ameliorates Detrusor Hyperactivity with Impaired Contractility via Transient Potential Vanilloid Channels: A Rat Model for Ovarian Hormone Deficiency.

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.

Influence of sex, age and thyroid function indices on dual-energy computed tomography-derived quantitative parameters of thyroid in patients with or without Hashimoto's thyroiditis.

PURPOSE: To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto's thyroiditis (HT). MATERIAL AND METHODS: A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann-Whitney U test, Student's T-test, and Spearman correlation analyses, respectively, as appropriate. RESULTS: HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p < 0.001). The volume was larger in male than that in female in overall study population and No-HT group (p = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p < 0.05). TPOAb and TgAb also correlated positively with IC in HT group (p = 0.002 and 0.007, respectively). CONCLUSION: DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid.

MicroRNA-143-3p ameliorates collagen-induced arthritis by polarizing naive CD4+ T cells into Treg cells.

BACKGROUND: Rheumatoid arthritis (RA) is a persistent and systemic autoimmunity disease. The abnormal differentiation of Treg cells is important in pathogenesis. Despite previous studies showed that microRNAs (miRNAs, miR) are pivotal modulators of Treg cells, the effect of miRNAs on Treg cell differentiation and function is not clear. Our study wants to reveal the relationship of miR-143-3p with the differentiative ability and biofunction of Treg cells during the development of RA. METHODS: The Expressing level of miR-143-3p and cell factor generation in peripheral blood (PB) of RA sufferers were identified by ELISA or RT-qPCR. The roles of miR-143-3p in Treg cell differentiation were studied via ShRNA/lentivirus transfection. Male DBA/1 J mice were separated into control, model, control mimics, and miR-143-3p mimics groups to analyze the anti-arthritis efficacy, the differentiative ability of Treg cells, and the expression level of miR-143-3p. RESULTS: Our team discovered that the Expressing level of miR-143-3p was related to RA disease activities in a negative manner, and remarkably related to antiinflammation cell factor IL-10. In vitro, the expression of miR-143-3p in the CD4+ T cells upregulated the percentage of CD4+ CD25+ Fxop3+ cells (Tregs) and forkhead box protein 3 (Foxp3) mRNA expression. Evidently, miR-143-3p mimic intervention considerably upregulated the content of Treg cells in vivo, validly avoided CIA progression, and remarkably suppressed the inflammatory events of joints in mice. CONCLUSION: Our findings indicated that miR-143-3p could ameliorate CIA through polarizing naive CD4+ T cells into Treg cells, which may be a novel strategy to treat autoimmune diseases such as RA.

Effects of Therapeutic Platelet-Rich Plasma on Overactive Bladder via Modulating Hyaluronan Synthesis in Ovariectomized Rat.

Postmenopausal women who have ovary hormone deficiency (OHD) may experience urological dysfunctions, such as overactive bladder (OAB) symptoms. This study used a female Sprague Dawley rat model that underwent bilateral ovariectomy (OVX) to simulate post-menopause in humans. The rats were treated with platelet-rich plasma (PRP) or platelet-poor plasma (PPP) after 12 months of OVX to investigate the therapeutic effects of PRP on OHD-induced OAB. The OVX-treated rats exhibited a decrease in the expression of urothelial barrier-associated proteins, altered hyaluronic acid (hyaluronan; HA) production, and exacerbated bladder pathological damage and interstitial fibrosis through NFƘB/COX-2 signaling pathways, which may contribute to OAB. In contrast, PRP instillation for four weeks regulated the inflammatory fibrotic biosynthesis, promoted cell proliferation and matrix synthesis of stroma, enhanced mucosal regeneration, and improved urothelial mucosa to alleviate OHD-induced bladder hyperactivity. PRP could release growth factors to promote angiogenic potential for bladder repair through laminin/integrin-α6 and VEGF/VEGF receptor signaling pathways in the pathogenesis of OHD-induced OAB. Furthermore, PRP enhanced the expression of HA receptors and hyaluronan synthases (HAS), reduced hyaluronidases (HYALs), modulated the fibroblast-myofibroblast transition, and increased angiogenesis and matrix synthesis via the PI3K/AKT/m-TOR pathway, resulting in bladder remodeling and regeneration.

The usability of an AAC pain description system for patients with acquired expressive communication disorders.

Augmentative and alternative communication (AAC) has been used by patients with acquired expressive communication disorders as an alternative to natural speech. The use of symbols to express pain, which is intangible, is challenging because designing a series of comprehensible symbols to represent personal experiences such as pain is not straightforward. This study describes (a) the development of symbols to express pain that were derived from Chinese pain-related similes and metaphors for an AAC mobile application developed specifically for this study known as PainDiary and (b) an assessment of the appropriateness of the app compared to conventional methods of collecting pain information. The symbols depicted headache pain and discomfort, which is prevalent among neurosurgical patients. The participants were 31 patients diagnosed with acquired expressive communication disorders who were receiving treatment in a neurosurgery general ward of Chang Gung Memorial Hospital in Taiwan and 14 nurses who worked on the ward. Pain information was collected by nurses using conventional methods and the PainDiary app. Assessment data, including the accuracy and efficiency of and user satisfaction with PainDiary, are compared. The results show that use of the app was effective in reporting pain and that patients required less time to report a pain event. The results further indicate that the PainDiary app was better received by younger individuals than by their older counterparts.

Panax notoginseng saponins (PNS) attenuate Th17 cell differentiation in CIA mice via inhibition of nuclear PKM2-mediated STAT3 phosphorylation.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with aberrant Th17 cell differentiation. Panax notoginseng (Burk.) F. H. Chen (Araliaceae) saponins (PNS) have an anti-inflammatory effect and can suppress Th17 cell differentiation. OBJECTIVE: To investigate mechanisms of PNS on Th17 cell differentiation in RA, and the role of pyruvate kinase M2 (PKM2). MATERIALS AND METHODS: Naive CD4+T cells were treated with IL-6, IL-23 and TGF-ß to induce Th17 cell differentiation. Apart from the Control group, other cells were treated with PNS (5, 10, 20 µg/mL). After the treatment, Th17 cell differentiation, PKM2 expression, and STAT3 phosphorylation were measured via flow cytometry, western blots, or immunofluorescence. PKM2-specific allosteric activator (Tepp-46, 50, 100, 150 µM) and inhibitor (SAICAR, 2, 4, 8 µM) were used to verify the mechanisms. A CIA mouse model was established and divided into control, model, and PNS (100 mg/kg) groups to assess an anti-arthritis effect, Th17 cell differentiation, and PKM2/STAT3 expression. RESULTS: PKM2 expression, dimerization, and nuclear accumulation were upregulated upon Th17 cell differentiation. PNS inhibited the Th17 cells, RORγt expression, IL-17A levels, PKM2 dimerization, and nuclear accumulation and Y705-STAT3 phosphorylation in Th17 cells. Using Tepp-46 (100 µM) and SAICAR (4 µM), we demonstrated that PNS (10 µg/mL) inhibited STAT3 phosphorylation and Th17 cell differentiation by suppressing nuclear PKM2 accumulation. In CIA mice, PNS attenuated CIA symptoms, reduced the number of splenic Th17 cells and nuclear PKM2/STAT3 signaling. DISCUSSION AND CONCLUSIONS: PNS inhibited Th17 cell differentiation through the inhibition of nuclear PKM2-mediated STAT3 phosphorylation. PNS may be useful for treating RA.

Interface between Two Immiscible Electrolyte Solutions Electrodes for Chemical Analysis.

The interface between two immiscible electrolyte solutions (ITIES) plays vital roles in various fields, such as neuroscience, environmental science, analytical chemistry, separation, catalysis, and nanoparticle synthesis. ITIES emerges as a unique approach in chemical analysis due to its sensitivity to both redox-active and redox-inactive analytes. Neurotransmitters, metal ions, drug molecules, and other complex molecules such as proteins have been detected using ITIES. The detection of redox-inactive species at the ITIES has opened a door to understanding a wide range of complex systems that are less suited to probing by solid electrodes. In this feature article, we present the history of electrochemistry at the ITIES; charge transfer reactions, thermodynamics, and kinetics at the ITIES; electrode-solution interfacial structure; and a diverse range of applications enabled by ITIES.

Study on the levels of N-nitrosamine compounds and untargeted metabolomics in patients with colorectal cancer.

Plasma samples were collected from 34 patients with advanced CRC and 92 healthy persons (control group), and the levels of 9 VNAs were measured using GC-MS. Untargeted metabolomics analysis was performed using LC-MS/MS. Partial least squares discriminant analysis (PLS-DA) and hierarchical cluster analysis were used to determine differential metabolites between the 2 groups. Receiver operating characteristic (ROC) curve analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed on the differential metabolites. It turned out that the detection rates of N-nitrosodimethylamine (NDMA) and N-nitrosopyrrolidine (NPYR) in patients with CRC were higher than in the control group (P < 0.05). N-nitrosomethylethylamine (NMEA) and N-nitrosodiphenylamine (NDPhA) were not detected in CRC patients. NDMA, N-nitrosodibutylamine (NDBA), N-nitrosopiperidine (NPIP), and NPYR were detected in male and female patients with CRC. There was no difference in VNAs exposure between the sexes of CRC patients. In the positive and negative ion mode, a total of 132 differential metabolites and 6 differential metabolic pathways were detected. Adenosine 5'-monophosphate, hypoxanthine, 11,12-epoxy-(5Z,8Z,11Z)-icosatrienoic acid, 16(R)-HETE, acetylcarnitine, and lysophosphatidic acid (LPA 20:5, LPA 20:4) were candidate biomarkers with higher predictive value. Hypoxanthine and xanthine metabolic pathways were associated with changes in VNAs in CRC patients. In summary, the effects of changes of VNAs in the plasma of CRC patients (especially NDMA and NPYR) on the progression of CRC should attract attention. Abnormalities of adenine and guanine and downstream hypoxanthine-xanthine metabolic pathways were closely related to changes of VNAs and metabolomics in CRC patients.

Simultaneous analysis of six inorganic anions in urine by double-suppress ion-exchange chromatography.

This study is aimed to establish a simple, rapid, and accurate ion chromatography approach for the simultaneous detection of six inorganic anions in urine. Various performance parameters affecting the determination of anions were optimized, including the selection of sample protein precipitation agent, eluent, and flow rate. The final eluent was 3.6 mmol/L sodium carbonate and 12% isopropanol with a flow rate of 0.6 mL/min. Acetonitrile was used for pretreatment to precipitate proteins, and the volume ratio of urine to acetonitrile was 1:4. The correlation coefficient of the target anion calibration curve ranged from 0.9973 to 0.9999. The limit of detection ranged from 1.50 to 12.0 µg/L, and the method detection limit ranged from 15.0 to 120 µg/L. The standard recovery rate for low, medium, and high concentrations ranged from 90 to 110%. The inter-day and intra-day relative standard deviations were <5%. The method has high accuracy and good reproducibility and is suitable for the separation and determination of anions in urine.

Triptolide inhibits Th17 differentiation via controlling PKM2-mediated glycolysis in rheumatoid arthritis.

CONTEXT: Rheumatoid arthritis (RA) is an autoimmune disease with the aberrant differentiation of T helper 17 (Th17) cells. Pyruvate kinase M2 (PKM2), a key enzyme of glycolysis, was associated with Th17 cell differentiation. AIM: To investigate the potential therapeutic effects of triptolide (TP) in collagen-induced arthritis (CIA) and Th17 cell differentiation, and elucidated the underlying mechanisms. METHODS: PKM2 expression and IL-17A production in peripheral blood of RA patients were detected by RT-qPCR or ELISA. Flow cytometry and ELISA were employed to assess the effect of Th17 cell differentiation by TP. PKM2 expression and other glycolysis-related factors were detected using RT-qPCR and Western Blot. PKM2 specific inhibitor Compound 3 K was used to verify the mechanisms. Male DBA/1J mice were divided into control, model, and TP (60 µg/kg) groups to assess the anti-arthritis effect, Th17 cell differentiation and PKM2 expression. RESULTS: PKM2 expression positively correlated with IL-17A production in RA patients. PKM2 expression was increased upon Th17 cell differentiation. Down-regulating PKM2 expression could strongly reduce Th17 cell differentiation. Molecular docking analysis predicted that TP targeted PKM2. TP treatment significantly reduced Th17 cell differentiation, PKM2 expression, pyruvate, and lactate production. In addition, compared with down-regulating PKM2 alone (Compound 3 K treatment), co-treatment with TP and Compound 3 K further significantly decreased PKM2-mediated glycolysis and Th17 cell differentiation. In CIA mice, TP repressed the PKM2-mediated glycolysis and attenuated joint inflammation. CONCLUSION: TP inhibited Th17 cell differentiation through the inhibition of PKM2-mediated glycolysis. We highlight a novel strategy for the use of TP in RA treatment.

Therapeutic Effect of Platelet-Rich Plasma Improves Bladder Overactivity in the Pathogenesis of Ketamine-Induced Ulcerative Cystitis in a Rat Model.

The present study attempted to elucidate whether intravesical instillation of platelet-rich plasma (PRP) could decrease bladder inflammation and ameliorate bladder hyperactivity in ketamine ulcerative cystitis (KIC) rat model. Female Sprague Dawley (S-D) rats were randomly divided into control group, ketamine-treated group, ketamine with PRP treated group, and ketamine with platelet-poor plasma (PPP) treated group. Cystometry and micturition frequency/volume studies were performed to investigate bladder function. The morphological change of bladder was investigated by Mason's trichrome staining. Western blotting analysis were carried out to examine the protein expressions of inflammation, urothelial differentiation, proliferation, urothelial barrier function, angiogenesis and neurogenesis related proteins. The results revealed that treatment with ketamine significantly deteriorated bladder capacity, decreased voiding function and enhanced bladder overactivity. These pathological damage and interstitial fibrosis may via NF-κB/COX-2 signaling pathways and muscarinic receptor overexpression. PRP treatment decreased inflammatory fibrotic biosynthesis, attenuated oxidative stress, promoted urothelial cell regeneration, and enhanced angiogenesis and neurogenesis, thereafter recovered bladder dysfunction and ameliorate the bladder hyperactivity in KIC rat model. These findings suggested that the PRP therapy may offer new treatment options for those clinical KIC patients.

Does surgical plethysmographic index-guided analgesia affect opioid requirement and extubation time? A systematic review and meta-analysis.

PURPOSE: This meta-analysis of all relevant clinical trials investigated surgical plethysmographic index (SPI)-guided analgesia's efficacy under general anesthesia for perioperative opioid requirement and emergence time after anesthesia. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched up to January 2022 to identify clinical trials comparing SPI-guided and conventional clinical practice for patients who underwent general anesthesia. With the random-effects model, we compared intraoperative opioid consumption, emergence time, postoperative pain, analgesia requirement, and incidence of postoperative nausea and vomiting (PONV). RESULTS: Thirteen randomized controlled trials (RCTs) (n = 1314) met our selection criteria. The overall pooled effect sizes of all RCTs indicated that SPI-guided analgesia could not significantly reduce opioid consumption during general anesthesia. SPI-guided analgesia accompanied with hypnosis monitoring could decrease intraoperative opioid consumption (standardized mean difference [SMD] - 0.31, 95% confidence interval [CI] - 0.63 to 0.00) more effectively than SPI without hypnosis monitoring (SMD 1.03, 95% CI 0.53-1.53), showing a significant difference (p < 0.001). SPI-guided analgesia could significantly shorten the emergence time, whether assessed by extubation time (SMD - 0.36, 95% CI - 0.70 to - 0.03, p < 0.05, I2 = 67%) or eye-opening time (SMD - 0.40, 95% CI - 0.63 to - 0.18, p < 0.001, I2 = 54%). SPI-guided analgesia did not affect the incidence of PONV, postoperative pain, and analgesia management. CONCLUSION: SPI-guided analgesia under general anesthesia could enhance recovery after surgery without increasing the postoperative complication risk. However, it did not affect intraoperative opioid requirement. Notably, SPI-guided analgesia with hypnosis monitoring could effectively reduce intraoperative opioid requirement.

Detection of Acetylcholine at Nanoscale NPOE/Water Liquid/Liquid Interface Electrodes.

The interface between two immiscible electrolyte solutions (ITIES) has become a very powerful analytical platform for sensing a diverse range of chemicals (e.g., metal ions and neurotransmitters) with the advantage of being able to detect non-redox electroactive species. The ITIES is formed between organic and aqueous phases. Organic solvent identity is crucial to the detection characteristics of the ITIES [half-wave transfer potential (E1/2), potential window range, limit of detection, transfer coefficient (α), standard heterogeneous ion-transfer rate constant (k0), etc.]. Here, we demonstrated, for the first time at the nanoscale, the detection characteristics of the NPOE/water ITIES. Linear detection of the diffusion-limited current at different concentrations of acetylcholine (ACh) was demonstrated with cyclic voltammetry (CV) and i-t amperometry. The E1/2 of ACh transfer at the NPOE/water nanoITIES was -0.342 ± 0.009 V versus the E1/2 of tetrabutylammonium (TBA+). The limit of detection of ACh at the NPOE/water nanoITIES was 37.1 ± 1.5 µM for an electrode with a radius of ∼127 nm. We also determined the ion-transfer kinetics parameters, α and k0, of TBA+ at the NPOE/water nanoITIES by fitting theoretical cyclic voltammograms to experimental voltammograms. This work lays the basis for future cellular studies using ACh detection at the nanoscale and for studies to detect other analytes. The NPOE/water ITIES offers a potential window distinct from that of the 1,2-dichloroethane (DCE)/water ITIES. This unique potential window would offer the ability to detect analytes that are not easily detected at the DCE/water ITIES.

High prevalence of HIV-1 transmitted drug resistance and factors associated with time to virological failure and viral suppression in Taiwan.

BACKGROUND: Integrase strand transfer inhibitor (InSTI)-based regimens have become the major first-line treatment for HIV-1-infected patients in Taiwan. Transmitted drug resistance (TDR) and several clinical characteristics are associated with time to virological failure or viral suppression; however, these have not been investigated in Taiwan. OBJECTIVES: To determine the impact of several factors on treatment outcomes in HIV-1-infected patients in Taiwan. METHODS: The cohort included 164 HIV-1 treatment-naive patients in Taiwan from 2018 to 2020. Blood specimens were collected to determine the genotypic drug resistance using the Stanford University HIV drug resistance database. Cox proportional hazards models were used to identify factors associated with time to virological failure or viral suppression. RESULTS: The prevalence of TDR in Taiwan was 27.4% and an increasing trend was seen from 2018 to 2020. TDR mutations related to NNRTIs were the most prevalent (21%) while TDR to InSTIs remained at a relatively low level (1.3%). A baseline HIV-1 viral load of ≥100 000 copies/mL was associated with a shorter time to virological failure [multivariate hazard ratio (mHR) 7.84; P = 0.018] and longer time to viral suppression (mHR 0.46; P < 0.001). Time to viral suppression was shorter in patients receiving InSTI-based regimens (mHR 2.18; P = 0.006). Different InSTI-based regimens as initial treatment did not affect the treatment outcomes. CONCLUSIONS: This study found an increasing trend of HIV-1 TDR prevalence from 2018 to 2020 in Taiwan. Baseline HIV-1 viral load and receiving InSTI-based regimens are important factors associated with time to virological failure or viral suppression.

MicroRNA-26b-5p alleviates murine collagen-induced arthritis by modulating Th17 cell plasticity.

Rheumatoid arthritis (RA) is a chronic autoimmune disease, and the abnormal differentiation of IL-17-producing T helper (Th17) cells is an important factor in the pathogenesis. Previous studies have shown that microRNAs (miRNAs, miR) act as key regulators of Th17 cells. However, the effects of miRNAs on Th17 cell differentiation and plasticity in RA are not clear. In this study, not only low miR-26b-5p expression and high IL-17A level were observed in the peripheral blood of RA patients, but also the negative correlation between miR-26b-5p and IL-17A was explored. The changes in collagen-induced arthritis (CIA) mice were consistent with those in RA patients. The results of in vitro experiments showed that miR-26b-5p mainly inhibited the initial differentiation of Th17 cells but did not impact the differentiation of induced-Treg into Th17-like cells. Meanwhile, miR-26b-5p mimics treatment alleviated inflammatory responses and reduced Th17 proportion in CIA mice. These results indicated that miR-26b-5p could alleviate the development of mice CIA by inhibiting the excessive Th17 cells, and that miR-26b-5p could modulate the plasticity of Th17 cell differentiation in RA, mainly block the initial differentiation. This may provide a novel strategy for the clinical treatment of RA.

The Effect of Telehealth Services on Provider Productivity.

BACKGROUND: Telehealth services historically have played a small role in the provision of health care in the United States. However during the coronavirus disease 2019 (COVID-19) pandemic, public and private insurers rapidly expanded access to telehealth in order to reduce exposure and avoid transmission. It is unknown whether telehealth will become a more regular substitute for in-person care beyond the pandemic. OBJECTIVE: Our objective was to provide evidence on the value of telehealth by comparing the productivity of physicians and other specialized clinicians who provide telehealth with the productivity of those who do not. RESEARCH DESIGN: We conducted a retrospective data analysis of 17,705 unique providers in the areas of internal medicine, cardiology, dermatology, psychiatry, psychology, and optometry practicing in the US veterans affairs health care system during the period 2015 to 2018. For each year, we measured individual providers productivity by the total number of relative value units (RVUs) per full-time equivalent (FTE). We estimated the impact of providing telehealth on RVUs/FTE using fixed effects regression models estimated on a panel dataset of 58,873 provider-year observations and controlling for provider and patient characteristics. RESULTS: Overall provider productivity increased in veterans affairs over the period, particularly in cardiology and dermatology. Providers of telehealth had above average productivity by 124 RVUs/FTE, or ∼4% of average total provider productivity. For the highest quartile of telehealth providers, average productivity was 188 RVUs/FTE higher than productivity of other providers. CONCLUSION: Strategies that encourage long-term integration of telehealth into provider practices may contribute to overall health care value.

Lower starting dose of afatinib for the treatment of metastatic lung adenocarcinoma harboring exon 21 and exon 19 mutations.

BACKGROUND: Afatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. METHODS: We designed a retrospective study, enrolling all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg daily afatinib as their initial treatment in three Kaohsiung Medical University-affiliated hospitals in Taiwan. RESULTS: A total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (75% vs. 83%, p = 0.1672), median PFS (14.5 vs. 14.8 months, log-rank p = 0.4649), and median OS (34.0 vs. 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients initially receiving 30 mg afatinib daily had fewer ADRs compared with those using 40 mg daily. The overall incidence of moderate and severe ADRs was significantly lower in patients receiving 30 mg afatinib daily compared with those using 40 mg daily (49% vs. 77%, p = 0.002); similar findings was observed in terms of severe ADRs (7% vs. 24%, p < 0.0001). CONCLUSION: Patients receiving 30 mg afatinib daily as their initial treatment had similar RR, PFS, OS, but significantly fewer serious ADRs, as compared with those using 40 mg as their starting dose.

An aryl thiol-vinyl azide coupling reaction and a thiol-vinyl azide coupling/cyclization cascade: efficient synthesis of ß-ketosulfides and arene-fused 5-methylene-2-pyrrolidinone derivatives.

The addition reaction of thiol to vinyl azide has been extensively studied. Variously substituted aryl thiols are all viable for this coupling process. The scope of the other partner is successfully expanded from α-aryl vinyl azide to α-alkyl vinyl azide. A thiol-vinyl azide coupling/cyclization cascade is realized with substituted aryl vinyl azides carrying a 2-methoxycarbonyl group. The value of ß-ketosulfide products was demonstrated by its application in S-heterocycle synthesis.