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Chemodynamic therapy (CDT) by triggering Fenton reaction or Fenton-like reaction to generate hazardous hydroxyl radical (•OH), is a promising strategy to selectively inhibit tumors with higher H2O2 levels and relatively acidic microenvironment. Current Fe-based Fenton nanocatalysts mostly depend on slowly releasing iron ions from Fe or Fe oxide-based nanoparticles, which leads to a limited rate of Fenton reaction. Herein, we employed black phosphorene nanosheets (BPNS), a biocompatible and biodegradable photothermal material, to develop iron-mineralized black phosphorene nanosheet (BPFe) by in situ deposition method for chemodynamic and photothermal combination cancer therapy. This study demonstrated that the BPFe could selectively increase cytotoxic ·OH in tumor cells whereas having no influence on normal cells. The IC50 of BPFe for tested tumor cells was about 3–6 μg/mL, which was at least one order of magnitude lower than previous Fe-based Fenton nanocatalysts. The low H2O2 level in normal mammalian cells guaranteed the rare cytotoxicity of BPFe. Moreover, the combination of photothermal therapy (PTT) with CDT based on BPFe was proved to kill tumors more potently with spatiotemporal accuracy, which exhibited excellent anti-tumor effects in xenografted MCF-7 tumor mice models.

Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear.To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition.This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms.During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings.Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Social perceptions of speakers are influenced by their voice information, including vocal characteristics and semantic content. Our study investigated how individuals’ warmth- and competence-related perceptions of speakers were affected by vocal pitch levels (i.e., high/low) and three kinds of semantic cues (i.e., prosocial, antisocial, and neutral) simultaneously. We have three key findings. First, antisocial cues negatively affected social perceptions, regardless of speakers’ gender. However, prosocial cues did not have positive impacts on evaluations of speakers because ratings were similar between prosocial cues and neutral cues. Second, female vocal pitch mattered for warmth-related perceptions but not for competence-related perceptions. The role of semantic cues should be additionally considered when investigating the impact of male vocal pitch on these perceptions. For example, higher-pitched men in prosocial contexts were perceived as warmer, while low-pitched men in antisocial contexts were judged as more competent. Third, the connection between vocal pitch and two kinds of perceptions showed an opposite trend, in which high pitch was related to more warmth but less competence, while the low pitch was associated with less warmth but more competence. These findings extend the understanding of the role of vocal pitch in the formation of stereotypes of strangers in different semantic contexts.

The concept of gingivoperiosteoplasty (GPP) in the mixed dentition stage as compared with secondary alveolar bone grafting (ABG) in management of alveolar cleft has not been much discussed upon. The authors present the experience with extensive GPP and ABG in the mixed dentition stage in complete bilateral alveolar cleft cases.A retrospective review of nonsyndromic patients with complete bilateral alveolar cleft operated on with either GPP or ABG (iliac crest) in the mixed dentition stage with at least 1-year follow-up was performed. Dental occlusal radiographs were evaluated for level of bone gain using Bergland and Witherow scales. Statistical evaluation of clinical success and procedure-related complications was conducted using χ2 test and odds ratio.Twenty-four patients in the GPP group and 20 in the ABG group were comparatively studied. Clinical success rate as indicated by Bergland scales I and II (87.5% in GPP vs 82.5% in ABG; P = 0.731), complication rate (20.83% in GPP vs 30% in ABG; P = 0.484), and status of canine eruption showed no significant differences in clinical outcomes in both groups.The technique of extensive GPP as described by authors shows equal efficacy to secondary ABG for management of bilateral alveolar clefts during the mixed dentition period.

Few surveys have focused on physician moral distress, burnout, and professional fulfilment. We assessed physician wellness and coping during the COVID-19 pandemic.Cross-sectional survey using four validated instruments.Sixty-two sites in Canada and the United States.Attending physicians (adult, pediatric; intensivist, nonintensivist) who worked in North American ICUs.None.We analysed 431 questionnaires (43.3% response rate) from 25 states and eight provinces. Respondents were predominantly male (229 [55.6%]) and in practice for 11.8 ± 9.8 years. Compared with prepandemic, respondents reported significant intrapandemic increases in days worked/mo, ICU bed occupancy, and self-reported moral distress (240 [56.9%]) and burnout (259 [63.8%]). Of the 10 top-ranked items that incited moral distress, most pertained to regulatory/organizational ( n = 6) or local/institutional ( n = 2) issues or both ( n = 2). Average moral distress (95.6 ± 66.9), professional fulfilment (6.5 ± 2.1), and burnout scores (3.6 ± 2.0) were moderate with 227 physicians (54.6%) meeting burnout criteria. A significant dose-response existed between COVID-19 patient volume and moral distress scores. Physicians who worked more days/mo and more scheduled in-house nightshifts, especially combined with more unscheduled in-house nightshifts, experienced significantly more moral distress. One in five physicians used at least one maladaptive coping strategy. We identified four coping profiles (active/social, avoidant, mixed/ambivalent, infrequent) that were associated with significant differences across all wellness measures.Despite moderate intrapandemic moral distress and burnout, physicians experienced moderate professional fulfilment. However, one in five physicians used at least one maladaptive coping strategy. We highlight potentially modifiable factors at individual, institutional, and regulatory levels to enhance physician wellness.

Intracranial gliomas are the most common primary central nervous system tumors in humans, and glioblastoma multiforme is the most malignant intracranial glioma. The nucleotide-binding domain leucine-rich repeat (NLR)-containing family are crucial regulators of inflammatory and innate immune responses. NLRP12 codes for the monarch-1 protein, which regulates immune responses in humans. Data from a next-generation sequencing database indicated that NLRP12 expression is increased in glioma cells. However, the relationship between NLRP12 levels and gliomas is unclear.To explore the role of NLRP12-related translation factors and proteins in glioma, we evaluated the clinical data and paraffin sections from glioma patients. The expression of NLRP12 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests.The degree of malignancy and prognosis highly correlated with NLRP12 levels. In addition, the siRNA-mediated downregulation of NLRP12 in glioma cell lines decreased proliferation, invasion, and migration. The levels of VEGF, N-cadherin, and cyclin D1 were downregulated after knockdown of NRLP12 in glioma cell lines, as observed using western blotting in vitro. Knockdown of NLRP12 attenuated the tumor progression in vivo.The expression of NLRP12 may be an independent prognostic factor and a potential target for the treatment of intracranial glioma.

Metabolic syndrome is a cluster of risk factors for cardiovascular disease afflicting more than 1 billion people worldwide and is increasingly being identified in younger age groups and in socioeconomically disadvantaged settings in the global south. Enteropathogen exposure and environmental enteropathy in infancy may contribute to metabolic syndrome by disrupting the metabolic profile in a way that is detectable in cardiometabolic markers later in childhood. A total of 217 subjects previously enrolled in a birth cohort in Amazonian Peru were monitored annually from ages 2 to 5 years. A total of 197 blood samples collected in later childhood were analyzed for 37 cardiometabolic biomarkers, including adipokines, apolipoproteins, cytokines, which were matched to extant early-life markers of enteropathy ascertained between birth and 2 years. Multivariate and multivariable regression models were fitted to test for associations, adjusting for confounders. Fecal and urinary markers of intestinal permeability and inflammation (myeloperoxidase, lactulose, and mannitol) measured in infancy were associated with later serum concentrations of soluble CD40-ligand, a proinflammatory cytokine correlated with adverse metabolic outcomes. Fecal myeloperoxidase was also associated with later levels of omentin-1. Enteric protozoa exposure showed stronger associations with later cardiometabolic markers than viruses, bacteria, and overall diarrheal episodes. Early-life enteropathy markers were associated with altered adipokine, apolipoprotein, and cytokine profiles later in childhood consistent with an adverse cardiometabolic disease risk profile in this cohort. Markers of intestinal permeability and inflammation measured in urine (lactulose, mannitol) and stool (myeloperoxidase, protozoal infections) during infancy may predict metabolic syndrome in adulthood.

Background. Asthma significantly impacts human life and health as a chronic disease. Traditional treatments for asthma have several limitations. Artificial intelligence aids in cancer treatment and may also accelerate our understanding of asthma mechanisms. We aimed to develop a new clinical diagnosis model for asthma using artificial neural networks (ANN). Methods. Datasets (GSE85566, GSE40576, and GSE13716) were downloaded from Gene Expression Omnibus (GEO) and identified differentially expressed CpGs (DECs) enriched by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Random forest (RF) and ANN algorithms further identified gene characteristics and built clinical models. In addition, two external validation datasets (GSE40576 and GSE137716) were used to validate the diagnostic ability of the model. Results. The methylation analysis tool (ChAMP) considered DECs that were up-regulated ( n =121) and down-regulated ( n =20). GO results showed enrichment of actin cytoskeleton organization and cell-substrate adhesion, shigellosis, and serotonergic synapses. RF (random forest) analysis identified 10 crucial DECs (cg05075579, cg20434422, cg03907390, cg00712106, cg05696969, cg22862094, cg11733958, cg00328720, and cg13570822). ANN constructed the clinical model according to 10 DECs. In two external validation datasets (GSE40576 and GSE137716), the Area Under Curve (AUC) for GSE137716 was 1.000, and AUC for GSE40576 was 0.950, confirming the reliability of the model. Conclusion. Our findings provide new methylation markers and clinical diagnostic models for asthma diagnosis and treatment.

Serine peptidase inhibitor Kazal type-1 (SPINK1), a trypsin kinase inhibitor, is known to be associated with inflammation and pathogenesis. The aim in this study was to demonstrate the clinicopathological role and progression of SPINK1 in rectal cancer (RC) patients undergoing concurrent chemoradiotherapy (CCRT). Immunohistochemical staining for SPINK1 protein expression in 111 RC cases revealed high SPINK1 expression was significantly associated with perineural invasion and poor CCRT response in pre-CCRT specimens. In addition, multivariable analyses showed that pre-CCRT SPINK1 expression was a significant prognostic marker of both overall and disease-free survival in RC patients receiving pre-operative CCRT; furthermore, in vitro studies demonstrated SPINK1 interacted with EGFR to promote the abilities of proliferation, migration and invasion attenuated by SPINK1 si-RNA via ERK, p38, and JNK pathways. SPINK1 was also found to regulate radio-resistance in CRC cell lines. In conclusion, SPINK1 expression is an independent prognostic marker in patients receiving pre-operative CCRT, and SPINK1 regulates proliferation, migration and invasion via EGFR-downstream ERK, p38 and JNK pathways. The phenotypes of radiosensitivity that could be reversed with attenuation of SPINK1 levels suggest that targeting SPINK1 might offer a strategy for optimal precision medicine.

Low molecular weight heparin (LMWH) has been given to reproductive-age women with various indications. This study aims to assess the benefits and risks of such use.We retrospectively reviewed data (n = 204) between Jan 2016 and May 2019. Logistic regression analysis was conducted to evaluate the correlation between indications and reproductive outcomes.LMWH use had higher odds of live birth in women less than 30 years of age (OR: 4.98; 95% CI = 1.13-21.98; p = 0.034) and with protein S deficiency (OR: 3.90; 95% CI = 1.77-8.59; p = 0.001). For the subgroup of recurrent pregnant loss, LMWH use was only advantageous to women with protein S deficiency (OR: 2.45; 95%:1.01-5.97; p = 0.048). Risks such as preterm delivery, small-for-gestational-age, placental abruption, antepartum/postpartum hemorrhage were not significantly increased among subgroups. Women treated with LMWH and who had successful live births (n = 171) had a slightly increased risk of postpartum hemorrhage compared to controls (n = 8058) during this period in our institution (2.9% vs 1.2%, p 0.001).LMWH administration produces a higher chance of live-birth to women younger than 30 years of age or with protein S deficiency. However, risk of postpartum hemorrhage is increased.

BDNF and its expressing neurons in the brain critically control feeding and energy expenditure (EE) in both rodents and humans. However, whether BDNF neurons would function in thermoregulation during temperature challenges is unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH

A retrospective cohort study was conducted to collect 465 patients with hepatitis B-related hepatocellular carcinoma who had undergone radical hepatectomy from January 1, 2012, to August 31, 2018, at the First Affiliated Hospital of the University of Science and Technology of China. The clinical, pathological, and follow-up information was collected to compare the basic characteristics of death and nondeath after radical resection. Kaplan–Meier curves were used for survival analysis and male and female subgroup analysis. The multivariate Cox proportional-hazards regression model was used to analyze independent risk factors related to postoperative death. Of the 465 patients with radical resection of hepatitis B-related hepatocellular carcinoma, 132 died, and 1-, 3-, and 5-year cumulative survival rates after operation were 92.1%, 78%, and 64%, respectively. In the male and female subgroup, 115 and 17 patients died, respectively. The 1-, 3-, and 5-year cumulative survival rates were 92.6%, 77.0%, and 62.6%, respectively, in men, and 89.6%, 78.8%, and 70.2%, respectively, in women. Multivariate Cox proportional-hazards regression analysis showed that microvascular invasion (MVI), Edmondson III/IV, BCLC stage B, and total bilirubin (TB) > 20.5 μmol/L were independent risk factors in patients with hepatitis B-related hepatocellular carcinoma after radical hepatectomy.

The aim of this study was to determine the effect of different exercise doses on weight loss in obese/overweight children. PubMed, Embase, SPORTDiscus, and the Cochrane library were searched from inception to November 2020 for randomized controlled trials. Fourty six trials involving 2,599 obese/overweight children were finally included. Different exercise dose interventions had different impacts. Exercise intervention reduce body weight (BW) by 1.46 kg (95% CI, −2.35 to −0.56, p=0.001), body fat percentage (BF%) by 2.24 (95% CI, −2.63 to −1.84, p2 (95% CI, −1.45 to −0.73, p2 (95% CI, −0.125 to −0.014, p=0.015) decrease in BMI. The findings suggest that there is a positive liner between exercise dose and weight loss, each MET-h/week associated with 0.147 kg, 0.060 and 0.069 kg/m2 decrease in body weight, BF%, BMI, respectively.

To determine the potential molecular mechanisms underlying the therapeutic effect of curcumin on hepatocellular carcinoma (HCC) by network pharmacology and experimental in vitro validation.The predictive targets of curcumin or HCC were collected from several databases. the identified overlapping targets were crossed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) platform. Two of the candidate pathways were selected to conduct an experimental verification. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide tetrazolium (MTT) assay was used to determine the effect of curcumin on the viability of HepG2 and LO2 cells. The apoptosis and autophagy of HepG2 cells were respectively detected by flow cytometry and transmission electron microscopy. Besides, western blot and real-time polymerase chain reaction (PCR) were employed to verify the p53 apoptotic pathway and adenosine 5'-monophosphate (AMP)‍-activated protein kinase (AMPK) autophagy pathway. HepG2 cells were pretreated with pifithrin-‍α (PFT-‍α) and GSK690693 for further investigation.The 167 pathways analyzed by KEGG included apoptosis, autophagy, p53, and AMPK pathways. The GO enrichment analysis demonstrated that curcumin was involved in cellular response to drug, regulation of apoptotic pathway, and so on. The in vitro experiments also confirmed that curcumin can inhibit the growth of HepG2 cells by promoting the apoptosis of p53 pathway and autophagy through the AMPK pathway. Furthermore, the protein and messenger RNA (mRNA) of the two pathways were downregulated in the inhibitor-pretreated group compared with the experimental group. The damage-regulated autophagy modulator (DRAM) in the PFT-‍α-pretreated group was downregulated, and p62 in the GSK690693-pretreated group was upregulated.Curcumin can treat HCC through the p53 apoptotic pathway and the AMPK/Unc-51-like kinase 1 (ULK1) autophagy pathway, in which the mutual transformation of autophagy and apoptosis may occur through DRAM and p62.

OBJECTIVES: The molecular landscape of non-muscle-invasive (NMIBC) and muscle-invasive (MIBC) bladder cancer based on molecular characteristics is essential but poorly understood. In this pilot study we aimed to identify a multi-omics signature that can distinguish MIBC from NMIBC. Such a signature can assist in finding potential mechanistic biomarkers and druggable targets.METHODS: Patients diagnosed with NMIBC (n = 15) and MIBC (n = 11) were recruited at a tertiary-care hospital in Nanjing from 1 April 2021, and 31 July 2021. Blood, urine and stool samples per participant were collected, in which the serum metabolome, urine metabolome, gut microbiome, and serum extracellular vesicles (EV) proteome were quantified. The differences of the global profiles and individual omics measure between NMIBC vs. MIBC were assessed by permutational multivariate analysis and the Mann-Whitney test, respectively. Logistic regression analysis was used to assess the association of each identified analyte with NMIBC vs. MIBC, and the Spearman correlation was used to investigate the correlations between identified analytes, where both were adjusted for age, sex and smoking status.RESULTS: Among 3168 multi-omics measures that passed the quality control, 159 were identified to be differentiated in NMIBC vs. MIBC. Of these, 46 analytes were associated with bladder cancer progression. In addition, the global profiles showed significantly different urine metabolome (p = 0.029), gut microbiome (p = 0.036), and serum EV (extracellular vesicles) proteome (p = 0.039) but not serum metabolome (p = 0.059). We also observed 17 (35%) analytes that had been developed as drug targets. Multiple interactions were obtained between the identified analytes, whereas for the majority (61%), the number of interactions was at 11-20. Moreover, unconjugated bilirubin (p = 0.009) and white blood cell count (p = 0.006) were also shown to be different in NMIBC and MIBC, and associated with 11 identified omics analytes.CONCLUSIONS: The pilot study has shown promising to monitor the progression of bladder cancer by integrating multi-omics data and deserves further investigations.

Chronic cluster headache (CH) substantially affects patients' quality of life, and treatment remains challenging. The current article reviewed controlled studies for new treatment options targeting calcitonin gene-related peptide (CGRP) or its receptors in CH and discussed the current gaps and future directions for the treatment of chronic CH.Two anti-CGRP monoclonal antibodies (i.e., galcanezumab and fremanezumab) completed randomized-control trials for efficacy for the preventive treatment of episodic and chronic CH. Galcanezumab was effective for preventing episodic CH but not chronic CH. Fremanezumab was ineffective in preventing episodic and chronic CH. Studies for other anti-CGRP monoclonal antibodies and CGRP antagonists are still pending for results. There are no randomized controlled trials for CGRP-targeted therapies that showed efficacy for chronic CH prevention. The different responses to galcanezumab between episodic and chronic CH may be due to the study design, i.e., the allowance of concomitant preventive therapies in the chronic CH study but not in the episodic CH study. Another reason for the discrepancies is the different roles and sensitivity of CGRP in chronic CH.

Urolithiasis is a common disease of the urinary system. Its recurrence rate is high and may increase medical expenses. Urine stones are composed of urine crystals and other impurities. We discovered the existence of autofluorescence in some of the urine crystals, especially in urolithiasis patients. The fluorescent molecule existed in urine crystals was verified and identified. We have applied micro-Raman and fluorescence microscopy to classify the urine crystals, used confocal laser scanning microscopy (CLSM) to examine the 3D images and spectra of autofluorescence in crystals, used Fourier transform infrared spectroscopy (FTIR) and mass spectrometry (MS) to identify the type of fluorophore in the autofluorescent urine crystals in urine. Riboflavin was identified as one of the major fluorophores in these autofluorescent urine crystals. The prevalence rates of the autofluorescent crystals in urolithiasis patients and subjects without the history of urolithiasis were to gather statistics. We observed that 80% of urolithiasis patients had autofluorescent crystals. Contrastingly, such crystals existed in only 7% of subjects without the history of urolithiasis. The presence of autofluorescent urine crystals may be linked to a sign of urolithiasis.

BACKGROUND AND PURPOSE Carotid blowout syndrome (CBS) is a devastating complication of head and neck cancer (HNC). In this study, we describe radiological features that can predict imminent (

The recommended US infant immunization schedule includes doses of diphtheria, tetanus, acellular pertussis (DTaP), inactivated poliovirus (IPV), Haemophilus influenzae type b (Hib) and hepatitis B virus (HepB) during the first 6 months of life. Little information is available about the timing of associated, complementary monovalent vaccine administration in infants receiving DTaP-based pentavalent combination vaccines.This was a retrospective cohort study of infants born between July 1, 2010, and June 30, 2018, in the US MarketScan commercial claims and encounters database. Descriptive statistics were used to assess vaccine administration patterns. Multivariate logistic regression was performed to explore factors associated with coadministration of DTaP-IPV/Hib and HepB.Among infants who received DTaP-HepB-IPV (n = 129,885), 93.7% had claims for at least 2 Hib doses; most (91.5%-98.3%) of these doses were administered on the same day as DTaP-HepB-IPV doses. Among infants who received DTaP-IPV/Hib (n=214,172), 95.3% had claims for ≥2 doses of HepB. Although coverage was high, 59.2% received the second HepB dose on the same day as the first DTaP-IPV/Hib dose, and 44.6% received the third dose of HepB on the same day as the third DTaP-IPV/Hib dose. Differences in coadministration of the second and third HepB doses with DTaP-IPV/Hib were associated with the region of residence, provider type, health plan type and coadministration of pneumococcal conjugate vaccine and rotavirus vaccine.Almost all infants received the appropriate, complementary monovalent vaccine series. However, this study found variability in the timing of HepB doses in relation to DTaP-IPV/Hib doses with many infants not completing the HepB series until 9 months of age.

Targeted temperature management (TTM) has been reported to improve outcomes in in-hospital cardiac arrest (IHCA) patients but little has been investigated into the relationship between prognoses and the blood urea nitrogen to creatinine ratio (BCR).A retrospective analysis of data from IHCA survivors treated with TTM between 2011 and 2018 was conducted based on the Research Patient Database Registry of the Partners HealthCare system in Boston. Serum laboratory data were measured during IHCA and within 24 hours after TTM completion. Intra-arrest and post-TTM BCRs were calculated, respectively. The primary outcome was neurologic status at discharge. The secondary outcome was in-hospital mortality.The study included 84 patients; 63 (75%) were discharged with a poor neurologic status and 40 (47.6%) died. Regarding poor neurological outcome at discharge, multivariate analysis revealed that post-TTM BCR was a significant predictor (adjusted OR, 1.081; 95% CI, 1.002-1.165; p = 0.043) and intra-arrest BCR was a marginal predictor (adjusted OR, 1.067; 95% CI, 1.000-1.138; p = 0.050). Post-TTM BCR had an acceptably predictive ability to discriminate neurological status at discharge, with an area under the receiver-operating characteristic curve of 0.644 (95% CI, 0.516-0.773) and a post-TTM BCR cutoff value of 16.7 had a sensitivity of 61.9% and a specificity of 70.0%.Post-TTM BCR was a significant predictor of the neurologic outcome at discharge among IHCA patients receiving TTM. IHCA patients with elevated intra-arrest BCR also had a borderline poor neurological prognosis at discharge.

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.

Anlotinib is an oral small-molecule multitarget tyrosine kinase inhibitor that hampers neovascularization thus providing antitumor effect. The ALTER 0303 trial was a multicenter, double-blind, phase 3 randomized clinical study to evaluate the efficacy of anlotinib in patients with advanced non-small cell lung cancer (NSCLC). The ALTER 0303 results showed that patients in the anlotinib group had a median progression-free survival of 5.4 months, a significant improvement compared with 1.4 months in the placebo group; however, median overall survival was only extended by 3.3 months (9.6 vs 6.3 months). The problem of anlotinib resistance cannot be ignored, and an in-depth exploration of biomarkers of anlotinib treatment response is urgently needed to further improve the efficacy of anlotinib in the treatment of NSCLC. This study aimed to identify plasma exosome markers that could be used to monitor the efficacy of anlotinib.We enrolled 5 patients with advanced NSCLC, and 15 blood samples were collected before anlotinib treatment, when the treatment was effective, and when the treatment was ineffective. The plasma exosomal RNA profiles were analyzed by whole-transcriptome sequencing at three different stages. The expression of dysregulated exosomal RNAs in 43 additional patients was also verified by real-time quantitative PCR.In the plasma exosomal RNA profiles of the 5 patients with advanced NSCLC during treatment with anlotinib, 7 miRNAs, 3 lncRNAs, and 83 mRNAs were significantly dysregulated. The regulation trend was opposite when the treatment was effective and ineffective, showing dynamic changes. After validation, we finally found that plasma exosomal lnc-SNAPC5-3:4 was significantly upregulated when anlotinib treatment was effective, and it was significantly downregulated when the treatment failed (p 0.05). Thus, it can be used as a potential biomarker for monitoring the efficacy of anlotinib.Our results demonstrate the potential of plasma exosomal lnc-SNAPC5-3:4 as a biomarker for monitoring anlotinib efficacy.

Antimicrobial resistance is one of the top 10 global public-health threats. Especially high rates of resistance have been reported for isolates from ICU patients, requiring expanded treatment options in this setting. We evaluated the activity of ceftolozane/tazobactam and comparators against Gram-negative isolates collected from patients with lower respiratory tract infections (LRTIs) in ICUs in seven Asian countries.In 2017-2019, up to 100 consecutive, aerobic Gram-negative LRTI isolates were collected per year at each of 37 hospitals. MICs were determined using the Clinical and Laboratory Standards Institute reference broth microdilution method.Overall, ceftolozane/tazobactam was active against 72% of 1408 Enterobacterales and 86% of 761 Pseudomonas aeruginosa isolates. Susceptibility to the non-carbapenem β-lactam comparators, including piperacillin/tazobactam, was 52-67% among Enterobacterales isolates, and the activity of all β-lactam comparators, including meropenem, was 57-70% among P. aeruginosa. Ceftolozane/tazobactam maintained activity against 61% of meropenem-nonsusceptible and 64% of piperacillin/tazobactam-nonsusceptible P. aeruginosa. At the country-level, ceftolozane/tazobactam activity ranged from90% against Enterobacterales from Hong Kong and South Korea to64% in Thailand and Vietnam, and from90% against P. aeruginosa from South Korea, Malaysia, Philippines and Taiwan to75% in Thailand and Vietnam. Correspondingly, the proportions of carbapenemase-positive isolates among Enterobacterales and P. aeruginosa isolates were highest in Thailand and Vietnam.Ceftolozane/tazobactam provides a potential treatment option for ICU patients in Asia, which is especially important considering the reduced activity of commonly used β-lactams against the studied ICU isolates. Knowledge of local resistance patterns should inform empirical therapy decision-making.

The outbreak of COVID-19 challenged the global health system and specifically impacted the emergency departments (EDs). Studying the quality indicators of ED care under COVID-19 has been a necessary task, and ED revisits have been used as an indicator to monitor ED performance.The study investigated whether discrepancies existed among ED revisiting cases before and after COVID-19 and whether the COVID-19 epidemic was a predictor of poor outcomes of ED revisits.Retrospective study.We used electronic health records data from a tertiary medical center. Data of patients with 72-h ED revisit after the COVID-19 epidemic were collected from February 2020 to June 2020 and compared with those of patients before COVID-19, from February 2019 to June 2019.The investigated outcomes included hospital admission, ICU admission, out-of-hospital cardiac arrest, and subsequent inhospital mortality. Univariate and multivariate logistic regression models were used to identify independent predictors of 72-h ED revisit outcomes.In total, 1786 patients were enrolled in our study - 765 in the COVID group and 1021 in the non-COVID group. Compared with the non-COVID group, patients in the COVID group were younger (53.9 vs. 56.1 years old; P = 0.002) and more often female (66.1% vs. 47.3%; P0.001) and had less escalation of triage level (11.6% vs. 15.0%; P = 0.041). The hospital admission and inhospital mortality rates in the COVID and non-COVID groups were 33.9% vs. 32.0% and 2.7% vs. 1.5%, respectively. In the logistic regression model, the COVID-19 period was significantly associated with inhospital mortality (adjusted odds ratio, 2.289; 95% confidence interval, 1.059-4.948; P = 0.035).Patients with 72-h ED revisits showed distinct demographic and clinical patterns before and after the COVID-19 epidemic; the COVID-19 period was an independent predictor of increased inhospital mortality.

IntroductionChronic conditions, such as diabetes, obesity, heart disease and depression, are highly prevalent and frequently co-occur with food insecurity in communities served by community health centres in the USA. Community health centres are increasingly implementing ‘Food as Medicine’ programmes to address the dual challenge of chronic conditions and food insecurity, yet they have been infrequently evaluated.Methods and analysisThe goal of this quasi-experimental study was to evaluate the effectiveness of Recipe4Health, a ‘Food as Medicine’ programme. Recipe4Health includes two components: (1) a ‘Food Farmacy’ that includes 16 weekly deliveries of produce and (2) a ‘Behavioural Pharmacy’ which is a group medical visit. We will use mixed models to compare pre/post changes among participants who receive the Food Farmacy alone (n=250) and those who receive the Food Farmacy and Behavioural Pharmacy (n=140). The primary outcome, fruit and vegetable consumption, and secondary outcomes (eg, food security status, physical activity, depressive symptoms) will be collected via survey. We will also use electronic health record (EHR) data on laboratory values, prescriptions and healthcare usage. Propensity score matching will be used to compare Recipe4Health participants to a control group of patients in clinics where Recipe4Health has not been implemented for EHR-derived outcomes. Data from surveys, EHR, group visit attendance and produce delivery is linked with a common identifier (medical record number) and then deidentified for analysis with use of an assigned unique study ID. This study will provide important preliminary evidence on the effectiveness of primary care-based strategies to address food insecurity and chronic conditions.Ethics and disseminationThis study was approved by the Stanford University Institutional Review Board (reference protocol ID 57239). Appropriate study result dissemination will be determined in partnership with the Community Advisory Board.

Background: Increasing evidence shows early vascular dysregulation in the pathophysiology of Alzheimer’s disease (AD) in elderly population. Objective: We wondered about the relationship between vascular health and cognitive performance in middle-aged adults. The present study aims to evaluate whether and which brain vascular hemodynamic parameters are associated with cognitive functions in a middle-aged, non-demented population. Methods: We recruited 490 middle-aged community-based participants (30–60 years). Transcranial color-coded sonography was used to measure cerebral vascular hemodynamics, including mean flow velocity, pulsatility index, and breath-holding index (BHI) in the middle cerebral arteries (MCAs). Cognitive functions were assessed using the Montreal Cognitive Assessment (MoCA). A multivariate linear regression model was used to determine the association between the MoCA scores and each intracranial hemodynamic parameter. Results: In 369 participants (median age 52 years [IQR 47–56], 48.8% men) with robust acoustic windows, the factors related to poorer MoCA scores were older age, less education extent, and the habitats of cigarette smoking or alcohol consumption. Multivariate analyses did not show a significant association between any intracranial hemodynamic parameters in both MCAs and MoCA scores in the total study population. Left MCA BHI was found to be significantly and independently correlated with the MoCA scores only in people aged 55–60 years (n = 111, B = 0.70, 95% confidence interval, 0.13–1.26, p = 0.017), however, not in people younger than 55 years. Conclusion: Our results emphasize the role of neurovascular abnormalities in the early pathophysiology of cognitive impairment and suggest cerebral vasoreactivity as the earliest detectable cognition-associated hemodynamic parameter.

Supplemental oxygen is often used to treat newborns with respiratory disorders. Exposure to high concentration of oxygen and long-term oxygen causes inflammation and acute lung injury. The acute inflammatory phase is followed by a fibroproliferative repair phase, leading to lung fibrosis. Many infants with lung fibrosis develop significant respiratory morbidities including reactive airways dysfunction and obstructive lung disease during childhood. Despite the absence of effective treatments and the incomplete understanding regarding mechanisms underlying fibrosis, extensive literature regarding lung fibrosis from in vitro and in vivo hyperoxia-exposed models is available. In this review, we discuss molecular mediators and signaling pathways responsible for increased fibroblast proliferation and collagen production, excessive extracellular matrix accumulation, and eventually, lung fibrosis. We discuss each of these mediators separately to facilitate clear understanding as well as significant interactions occurring among these molecular mediators and signaling pathways.

Although no human papillomavirus (HPV) vaccine is indicated for single-dose administration, some observational evidence suggests that a 1-dose regimen might reduce HPV infection risk to that achieved with 2 doses. This study estimated the potential health and economic outcomes associated with switching from a 2-dose HPV vaccination program for girls and boys aged 13-14 years to an off-label 9-valent (9vHPV), 1-dose regimen, accounting for the uncertainty of the effectiveness and durability of a single dose. A dynamic HPV transmission infection and disease model was adapted to the United Kingdom and included a probabilistic sensitivity analysis using estimated distributions for duration of protection of 1-dose and degree of protection of 1 relative to 2 doses. One-way sensitivity analyses of key inputs were performed. Outcomes included additional cancer and disease cases and the difference in net monetary benefit (NMB). The 1-dose program was predicted to result in 81,738 additional HPV-related cancer cases in males and females over 100 years compared to the 2-dose program, ranging from 36,673 to 134,347 additional cases (2.5% and 97.5% quantiles, respectively), and had a 7.8% probability of being cost-effective at the £20,000/quality-adjusted life years willingness-to-pay (WTP) threshold. In one-way sensitivity analyses, the number of additional cancer cases was sensitive to the median of the duration of protection distribution and coverage rates. The differences in NMBs were sensitive to the median of the duration of protection distribution, dose price and discount rate, but not coverage variations. Across sensitivity analyses, the probability of 1 dose being cost-effective vs 2 doses was 50% at the standard WTP threshold. Adoption of a 1-dose 9vHPV vaccination program resulted in more vaccine-preventable HPV-related cancer and disease cases in males and females, introduced substantial uncertainty in health and economic outcomes, and had a low probability of being cost-effective compared to the 2-dose program.

Post-transplant cyclophosphamide (PT-Cy) and calcineurin inhibitors used in peripheral blood haplo-identical stem cell transplantation (haploSCT) increase the risk of acute/chronic graft-versus-host disease (GVHD). Whether ATG/PT-Cy is feasible for Asian patients undergoing haploSCT is unclear, and an optimal strategy for GVHD prophylaxis is needed.We retrospectively analyzed 61 hematologic malignancy patients who underwent peripheral blood haploSCT using ATG/PT-Cy from January 2013 to December 2018. We also compared the effects of ATG/PT-Cy (ATG group; n = 61) with historical data from patients who underwent haploSCT using sirolimus/PT-Cy (non-ATG group; n = 22).Cumulative incidences of grades II-IV acute GVHD and moderate to severe chronic GVHD did not differ significantly. The ATG group had higher incidence of Epstein-Barr virus (EBV) reactivation, but neither group had post-transplant lymphoproliferative disorders. The ATG group also had a higher OS rate (2-year OS in ATG group vs. non-ATG group: 43.4% vs. 27.3%, respectively; P = 0.071).ATG/PT-Cy is an acceptable strategy for GVHD prophylaxis in Asian patients undergoing haploSCT.

To evaluate the efficacy and safety of intravenous iron supplementation in patients with renal anaemia.We searched the PubMed, Embase, Cochrane Library, and Web of Science from their inception until 17 September 2021, for randomized controlled trials (RCTs) to evaluate the efficacy and safety of intravenous iron at different frequencies. The observed efficacy indicators included transfer saturation (TSAT), serum ferritin (SF) and haemoglobin (HGB). Outcomes of interest included allergies, infections, all-cause mortality and cardiovascular events.Of the 751 eligible studies, 7 RCTs met the inclusion criteria. The RCTs showed that there were no significant differences between the low-frequency high-dose group (1-2 doses,200 mg/dose) and the high-frequency low-dose group (4-5 doses, ≤200 mg/dose) in the increase in TSAT (WMD = 1.90; 95% CI = -2.04 to 5.84; IFrequencies of intravenous iron supplementation with similar doses share similar safety and efficacy in patients with renal anaemia. However, a single dose or two doses of intravenous iron are more cost-effective and patient friendly. These findings may provide evidence for the clinical application of intravenous iron supplementation for patients with renal anaemia.

To determine the realized tumor to normal ratios (TNRs) in patients undergoing radiation segmentectomies (RS); determine the relationship between TNRs and particle load in transarterial radioembolization (TARE).In total, 148 patients who underwent 184 TARE procedures for hepatocellular carcinoma were evaluated. Post treatment SPECT CT bremsstrahlung imaging was analyzed utilizing Simplicit90y™ to determine realized TNR. A model which normalized activity across all RS treatments to a level that would achieve 400 Gy by unicompartmental dosing was created to determine the affect realized TNR would have on tumor absorbed dose.The mean TNR in the setting of RS was 2.88 ± 1.60 and was higher for glass as compared to resin microspheres (3.07 ± 1.68 vs 2.24 ± 1.21, p = 0.01). The TNR was significantly greater in the RS as compared to the lobar deliveries (2.88 ± 1.60 vs 2.16 ± 1.12, p 0.01). When normalizing the activity of RS treatments to the level required to achieve 400 Gy by unicompartmental calculations, there was found to be significant differences in the predicted tumor absorbed dose when separated by the median tumor dose (601.2 ± 133.3 vs 1146.9 ± 297.5, p 0.01) or median realized TNR (1119.2 ± 341 Gy vs 635.7 ± 160.2 Gy, p 0.01). Particle load was found to be associated with TNR on univariate (p 0.01) and multivariate (p 0.01) analysis.Significant TNRs are seen in RS and perhaps argue for the use of multi-compartmental dosimetry techniques in this setting and particle load may affect TNR.• Tumor to normal ratios were significantly higher in radiation segmentectomies than lobar deliveries. • Tumor to normal ratios were significantly higher when utilizing glass, as compared to resin microspheres. • When creating a model that prescribed the activity required to reach 400 Gy by MIRD, realized tumor dose varied significantly in radiation segmentectomies.

Despite the continual improvements in dialysis treatments, mortality in end-stage kidney disease (ESKD) remains high. Many mortality prediction models are available, but most of them are not precise enough to be used in the clinical practice. We aimed to develop and validate two prediction models for 3-month and 1-year patient mortality after dialysis initiation in our population.Using population-based data of insurance claims in Taiwan, we included more than 210,000 patients who initiated dialysis between January 1, 2006, and June 30, 2015. We developed two prognostic models, which included 9 and 11 variables, respectively (including age, sex, myocardial infarction, peripheral vascular disease, cerebrovascular disease, dementia, chronic pulmonary disease, peptic ulcer disease, malignancy, moderate to severe liver disease, and first dialysis in intensive care unit).The models showed adequate discrimination (C-statistics were 0.80 and 0.82 for 3-month and 1-year mortality, respectively) and good calibration. In both our models, the first dialysis in the intensive care unit and moderate-to-severe liver disease were the strongest risk factors for mortality.The prediction models developed in our population had good predictive ability for short-term mortality in patients initiating dialysis in Taiwan and could help in decision-making regarding dialysis initiation, at least in our setting, supporting a patient-centered approach to care.

To compare the efficacy of different treatments for posterior semicircular canal benign paroxysmal positional vertigo (PC-BPPV) by using direct and indirect evidence from existing randomized data.Randomized case-control studies that compared the efficacy of various nonsurgical treatments in PC-BPPV patients at 1 week and 1 month of follow-up were comprehensively screened. Bayesian network meta-analysis was performed to evaluate direct and indirect treatment comparisons. We further conducted subgroup pairwise meta-analysis to explore the inconsistency between comparisons of the Epley versus a sham maneuver and the Epley versus the Semont maneuver.A total of 41 parallel, randomized controlled studies were included. The Epley with vestibular rehabilitation (EVR), Epley, Semont and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test at 1 week of follow-up (odds ratios [ORs]: 11.41-23.8, 95% credible interval [CrI]: excluding null), among which EVR showed the best efficacy (the surface area under the cumulative ranking curves [SUCRA] = 77.5%). However, at 1 month of follow-up, only the Semont (rank first, SUCRA = 76.1%) and Epley maneuvers (rank second, SUCRA = 65.3%) were effective in eliminating nystagmus during a Dix-Hallpike test. In the pairwise subgroup meta-analysis, for patients younger than 55 years of age, the efficacy of the Epley maneuver was comparable to that of the Semont maneuver [rate ratio (RR): 0.99, 95% confidence interval (CI): 0.93-1.05]; for patients with a longer duration before treatment, the effect of the Epley maneuver was equivalent to that of a sham maneuver (RR: 1.07, 95% CI: 0.90-1.29).Among the 12 types of PC-BPPV treatments, the Epley, Semont, EVR, and Hybrid maneuvers were effective in eliminating nystagmus during a Dix-Hallpike test for PC-BPPV at 1 week of follow-up, whereas only the Epley and Semont maneuvers were effective at 1 month of follow-up. The duration before treatments and the age of patients might contribute to the efficacy of treatments.

GALNT14-rs9679162 "TT" genotype is associated with favorable clinical outcomes in hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE). We investigated whether patients with GALNT14-rs9679162 "non-TT" unfavorable genotype benefited from chemoembolization plus sorafenib combination therapy.Intermediate stage HCC patients were recruited for GALNT14-rs9679162 genotyping before TACE. Patients with "TT" genotype received only TACE, labeled as TT (TACE) group. Patients with "non-TT" genotype ("GG" or "GT") were randomized to receive either TACE alone, labeled as Non-TT (TACE) group, or TACE plus sorafenib, labeled as Non-TT (TACE + Sora) group. The latter group received sorafenib 400 mg daily plus TACE.From October 2015 to April 2019, 103 HCC patients scheduled to receive chemoembolization were screened. Of them, 84 met inclusion criteria and were assigned to TT (TACE) (n = 25), Non-TT (TACE) (n = 30) and Non-TT (TACE + Sora) (n = 29) groups according to their GALNT14 genotypes. Repeated TACE sessions were performed on-demand and patients were followed until November 2020. It was found that TT (TACE) and Non-TT (TACE + Sora) patients had shorter time-to-complete response compared with that in Non-TT (TACE) patients (p 0.001 and 0.009, respectively). These two groups also had longer time-to-TACE progression (p 0.001 and 0.006, respectively) and longer progression-free survival (p = 0.001 and 0.021, respectively). However, TT (TACE) patients harbored longer overall survival compared with those in non-TT (TACE + Sora) and non-TT (TACE) patients (p = 0.028, 0.001, respectively).Combination of sorafenib and TACE for "non-TT" patients partially overcame the genetic disadvantage on treatment outcomes in terms of time-to-complete response, time-to-TACE progression and progression-free survival.ClinicalTrials.gov NCT02504983.

Background Obesity is rapidly globally increasing. Meanwhile, there is an increase in negative perception of the body image and, consequently, an increase in weight control management. Body perception plays an important mediating role between overweight or obesity and weight control behaviours. This study aims to examine whether body perception is associated with dietary weight management behaviours among Chinese children and adolescents. Methods Child body perception and health behaviours from Chinese Health and Nutrition Survey (2015) were assessed, and 729 boys and 640 girls who aged 6 to 17 years were included in this study. Variables assessed as covariates were sociodemographic, physical activity and body perception involving self-perceptive weight status and body image dissatisfaction (BID). Multivariate logistic regression was used to explore the association between dietary weight management behaviours and body perception. Results 60.77% students rightly matched their body mass index (BMI) with self-perceived weight. The prevalence of BID was 59.39%. After adjustment for sociodemographic information, physical activities and BMI, those whose self-perceived weight status as overweight/obesity were associated with an increased risk of dietary weight management behaviours comparing to those who have normal weight in boys (OR = 5.07; 95% CI = 1.86, 13.87; P P P Conclusions The results revealed that body perception had a significant association with dietary weight management behaviours and exited the discrepancy according to sex. It is necessary to promote healthy awareness of body perception and to establish self-motivation for improving basic health knowledge in school health education activities.

Kiwifruit puree was treated with high and normal temperatures and pressures as independent variables to determinate the structural changes of chlorophyll derivatives. Two groups of colored elution samples were identified as single component compounds by High Performance Liquid Chromatography (HPLC). In addition, the structures of the two compounds were identified and analyzed by High Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR). The results of HRMS and NMR demonstrate that components 1 and 2 were hydroxymethylbilane (HMB) and red chlorophyll catabolite (RCC), respectively, and indicate that HMB and RCC were the main pigments in the chlorophyll compounds after high temperature and pressure treatment. Furthermore, the cleavage pathway of the RCC in kiwifruit puree has been discussed, which provides a theoretical basis for the color protection of kiwifruit products in the course of processing.

Background The coexistence of sarcopenia and dementia in aging populations is not uncommon, and they may share common risk factors and pathophysiological pathways. This study aimed to evaluate the relationship between brain atrophy and low lean mass in the elderly with impaired cognitive function. Methods This cross-sectional study included 168 elderly patients who visited the multi-disciplinary dementia outpatient clinic at Kaohsiung Chang Gung Memorial Hospital for memory issues, between 2017 and 2019. The body composition was assessed by dual energy X-ray absorptiometry (DEXA) and CT based skeletal muscle index including L3 skeletal muscle index (L3SMI) and masseter muscle mass index (MSMI). The brain atrophy assessment was measured by CT based visual rating scale. Possible predictors of low lean mass in the elderly with cognitive impairement were identified by binary logistic regression. ROC curves were generated from binary logistic regression. Results Among the 81 participants, 43 (53%) remained at a normal appendicular skeletal muscle index (ASMI), whereas 38 (47%) showed low ASMI. Compared with the normal ASMI group, subjects with low ASMI exhibited significantly lower BMI, L3SMI, and MSMI (all p p Conclusions Global cortical atrophy and body mass index combined with either L3 skeletal muscle index or masseter skeletal muscle index can predict low lean mass in the elderly with cognitive impairment.

BACKGROUND Prisoners are at risk of hepatitis C virus (HCV) infection, especially among the people who inject drugs (PWID). We implemented an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic direct-acting antivirals (DAA) regimen, 12 wk of sofosbuvir/velpatasvir, in a PWID-dominant prison in Taiwan. AIM To implement an outreach strategy in combination with universal mass screening and immediate onsite treatment with a simplified pan-genotypic DAA regimen in a PWID-dominant prison in Taiwan. METHODS HCV-viremic patients were recruited for onsite treatment program for HCV micro-elimination with a pangenotypic DAA regimen, 12 wk of sofosbuvir/ velpatasvir, from two cohorts in Penghu Prison, either identified by mass screen or in outpatient clinics, in September 2019. Another group of HCV-viremic patients identified sporadically in outpatient clinics before mass screening were enrolled as a control group. The primary endpoint was sustained virological response (SVR12, defined as undetectable HCV ribonucleic acid (RNA) 12 wk after end-of-treatment). RESULTS A total of 212 HCV-viremic subjects were recruited for HCV micro-elimination campaign; 91 patients treated with sofosbuvir/Ledipasvir or glecaprevir/ pibrentasvir before mass screening were enrolled as a control. The HCV micro-elimination group had significantly lower proportion of diabetes, hypertension, hyperlipidemia, advanced fibrosis and chronic kidney diseases, but higher levels of HCV RNA. The SVR12 rate was comparable between the HCV micro-elimination and control groups, 95.8% (203/212) vs 94.5% (86/91), respectively, in intent-to-treat analysis, and 100% (203/203) vs 98.9% (86/87), respectively, in per-protocol analysis. There was no virological failure, treatment discontinuation, and serious adverse event among sofosbuvir/velpatasvir-treated patients in the HCV micro-elimination group. CONCLUSION Outreach mass screening followed by immediate onsite treatment with a simplified pangenotypic DAA regimen, sofosbuvir/velpatasvir, provides successful strategies toward HCV micro-elimination among prisoners.

Hyperuricemia (HUA) and its associated metabolic diseases seriously threaten human health, and commensal microbiota has been identified as one of the environmental triggers of HUA. The role of berberine (BBR) in the treatment of HUA has begun to receive attention in recent years. However, how BBR modulates the microbiota to slow HUA progression is unclear. In this study, we showed that BBR alleviated potassium oxonate (PO)-induced HUA in mice by suppressing the expression of xanthine oxidase (XOD) in the liver and urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) in the kidney. The BBR also improved renal inflammation by inhibiting the expression of TNF-[Formula: see text], IL-1[Formula: see text], and caspase-1. Subsequently, we evaluated whether the observed anti-HUA effects of BBR were associated with changes in gut microbial structure in mice. 16S rRNA sequencing data showed that BBR significantly altered the community compositional structure of the gut microbiota. Specifically, BBR enriched the abundance of Coprococcus, Bacteroides, Akkermansia, and Prevotella. Antibiotic treatment can reverse the anti-HUA effects of BBR that further supports the role of the gut microbiota. In conclusion, our study provides evidence that BBR ameliorates PO-induced HUA by modulating the gut microbiota.

Background The COVID-19 pandemic has disrupted healthcare, including immunization practice and well child visit attendance. Maintaining vaccination coverage is important to prevent disease outbreaks and morbidity. We assessed the impact of the COVID-19 pandemic on pediatric and adolescent vaccination administration and well child visit attendance in the United States. Methods This cross-sectional study used IBM MarketScan Commercial Database (IMC) with Early View (healthcare claims database) and TriNetX Dataworks Global Network (electronic medical records database) from January 2018–March 2021. Individuals ≤ 18 years of age who were enrolled during the analysis month of interest (IMC with Early View) or had ≥ 1 health encounter at a participating institution (TriNetX Dataworks) were included. We calculated the monthly percent difference between well child visit attendance and vaccine administration rates for 10 recommended pediatric/adolescent vaccines in 2020 and 2021 compared with 2018–2019. Data were stratified by the age groups 0–2 years, 4–6 years, and 9–16 years. Results In IMC with Early View, the average monthly enrollment for children 0–18 years of age was 5.2 million. In TriNetX Dataworks, 12.2 million eligible individuals were included. Well child visits and vaccinations reached the lowest point in April 2020 compared with 2018–2019. Well child visit attendance and vaccine administration rates were inversely related to age, with initial reductions highest for adolescents and lowest for ages 0–2 years. Rates rebounded in June and September 2020 and stabilized to pre-pandemic levels in Fall 2020. Rates dropped below baseline in early 2021 for groups 0–2 years and 4–6 years. Conclusions We found substantial disruptions in well child visit attendance and vaccination administration for children and adolescents during the COVID-19 pandemic in 2020 and early 2021. Continued efforts are needed to monitor recovery and catch up to avoid outbreaks and morbidity associated with vaccine-preventable diseases.

Objective To assess the predictive value of swab cultures of cryopreserved skull flaps during cranioplasties for surgical site infections (SSIs). Methods A retrospective review was conducted of consecutive patients who underwent delayed cranioplasties with cryopreserved autografts between 2009 and 2017. The results of cultures obtained from swabs and infected surgical sites were assessed. The accuracy, sensitivity, and specificity of swab cultures for SSIs were evaluated. Results The study included 422 patients categorized into two groups, swab and nonswab, depending on whether swab cultures were implemented during cranioplasties. The overall infection rate was 7.58%. No difference was seen in infection rates between groups. There were 18 false-positive and no true-positive swab culture results. All bacteria between swab cultures and SSI cultures were discordant. Meanwhile, there were 19 false-negative swab cultures. The results showed high specificity but low sensitivity for swab cultures to predict SSI occurrence and the pathogens. Conclusions Owing to low accuracy and sensitivity, swab cultures of cryopreserved autografts should not be routinely performed during delayed cranioplasties.

Objective This retrospective study analyzed the outcomes of patients undergoing complete or incomplete unilateral cleft lip repair using the Chang Gung technique. The goal was to compare the symmetry and change of the technique through the measurement of anthropometric points on digital photographs. Methods From 2010 to 2016, a total of 274 complete and incomplete cleft lip patients without other craniofacial deformities were included in the study. All included patients had a minimum 1-year follow-up with frontal view photographs taken. The vermilion area, lip width, vermilion height, lateral lip length, lip height, and Cupid's bow width of both cleft and noncleft sides were measured for all patients. The Cleft Lip Component Symmetry Index was used to determine the symmetry of the cleft and noncleft sides in both incomplete and complete cleft groups. Results A total of 152 complete and 122 incomplete cleft lip patients were included in the study. The mean Cleft Lip Component Symmetry Index values showed that the vermilion area, lip height, and Cupid's bow width were symmetric on both cleft and noncleft sides. Lip width and lateral lip length were noted to be shorter, whereas the vermilion height was thicker on the cleft side than on the noncleft side. Significant differences between the complete and incomplete cleft group measurements were found for lateral lip length and lip height, and complete cleft measurements were shorter than those for incomplete clefts. There were no significant differences in vermilion area, lip width, vermilion height, and Cupid's bow width. Conclusions The outcome analysis showed that vermilion height reduction and modifications could be made for both complete and incomplete groups. The complete cleft lip has been found to have a significantly shorter lateral lip length and lip height, reflecting a more severe anatomical soft tissue deficiency in this group. A long-term outcome anthropometric point study may further verify the results of this surgical technique.

ObjectiveStromal barriers, such as the abundant desmoplastic stroma that is characteristic of pancreatic ductal adenocarcinoma (PDAC), can block the delivery and decrease the tumour-penetrating ability of therapeutics such as tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), which can selectively induce cancer cell apoptosis. This study aimed to develop a TRAIL-based nanotherapy that not only eliminated the extracellular matrix barrier to increase TRAIL delivery into tumours but also blocked antiapoptotic mechanisms to overcome TRAIL resistance in PDAC.DesignNitric oxide (NO) plays a role in preventing tissue desmoplasia and could thus be delivered to disrupt the stromal barrier and improve TRAIL delivery in PDAC. We applied an in vitro–in vivo combinatorial phage display technique to identify novel peptide ligands to target the desmoplastic stroma in both murine and human orthotopic PDAC. We then constructed a stroma-targeted nanogel modified with phage display-identified tumour stroma-targeting peptides to co-deliver NO and TRAIL to PDAC and examined the anticancer effect in three-dimensional spheroid cultures in vitro and in orthotopic PDAC models in vivo.ResultsThe delivery of NO to the PDAC tumour stroma resulted in reprogramming of activated pancreatic stellate cells, alleviation of tumour desmoplasia and downregulation of antiapoptotic BCL-2 protein expression, thereby facilitating tumour penetration by TRAIL and substantially enhancing the antitumour efficacy of TRAIL therapy.ConclusionThe co-delivery of TRAIL and NO by a stroma-targeted nanogel that remodels the fibrotic tumour microenvironment and suppresses tumour growth has the potential to be translated into a safe and promising treatment for PDAC.

The skin serves as a physical barrier and an immunological interface that protects the body from the external environment

Yunnan is the first place where human immunodeficiency virus type 1 (HIV-1) became prevalent in China, and it is also the place with the most complicated HIV-1 genetic diversity in China. On October 23, 2019, a patient newly diagnosed with acquired immunodeficiency syndrome from a hospital in Baoshan, Yunnan, was recruited for genetic analysis. Near full-length genome of HIV-1 was amplified from the plasma sample. Phylogenetic analysis revealed that this sequence (BS6F24) has a close relationship with CRF86_BC and a unique recombinant form (URF) (KY406739), which was formed by recombination of subtypes B and C. Bootscan analysis confirmed that the first part (HXB2:1022-5832) and last part (HXB2:5833-9120) genomes of BS6F24 had the same recombinant structures as KY406739 and CRF86_BC, respectively. A second-generation recombinant form that originated from CRF86_BC and a URF were reported for the first time. This indicates the need for continuous monitoring of the genetic diversity of HIV-1 in Yunnan, China.

Whether the electrocardiography (ECG) serial changes predict outcomes in cardiac arrest survivors undergoing therapeutic hypothermia remains unclear.This retrospective observational study enrolled 366 adult nontraumatic cardiac arrest survivors who underwent therapeutic hypothermia in a tertiary transfer center during 2006-2018. The ECG at return of spontaneous circulation (ROSC), during hypothermia and after rewarming were analyzed. 295 cardiac arrest survivors were included. Compared with the survivors, the non-survivors had longer QRS durations at the ROSC (118.33 ± 32.47 ms vs 106.88 ± 29.78 ms, p 0.001) and after rewarming (99.26 ± 25.07 ms vs 93.03 ± 19.09 ms, p = 0.008). The enrolled patients were classified into 4 groups based on QRS duration at the ROSC and after rewarming, namely (1) narrow-narrow (narrow QRS at ROSC and narrow QRS after rewarming, n = 156), (2) narrow-wide (n = 29), (3) wide-narrow (n = 87), and (4) wide-wide (n = 23) group. The wide-wide group had the worst survival rates [odds ratio (OR) = 0.141, p = 0.001], followed by the narrow-wide group (OR 0.223, p = 0.003) and the wide-narrow group (OR 0.389, p = 0.003).In cardiac arrest survivors given therapeutic hypothermia, QRS durations at the ROSC, after rewarming and their changes may predict survival to hospital discharge.