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PurposeTransforming growth factor β (TGFβ) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFβ has not been ideal. Targeting TGFβ with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFβ-targeting peptide P144 coupled with [68Ga] in a PANC-1 tumor model.ProceduresTGFβ-targeting inhibitory peptide P144 with stable activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model.Results[68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga-P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect.Conclusion[68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies.

BackgroundPrevious experimental studies have shown that mice overexpressing amyloid precursor protein, in which β-amyloid (Aβ) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Aβ on insulin action and insulin secretion in vitro and the association of plasma Aβ with prediabetes in human.MethodsWe examined the effects of Aβ40 and Aβ42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses.ResultsIn the in vitro studies, Aβ40 and Aβ42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Aβ40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Aβ42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Aβ40 and Aβ42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively.ConclusionElevated plasma Aβ40 and Aβ42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic β-cells.

BackgroundWith the development trend of healthy aging and intelligent integration, escort products have become a new means of healthy aging. Healthy old-age care pays attention to the convenience and informatization of life. To meet the needs, designers often design multiple accompanying product solutions, and it is very important to use reasonable evaluation methods to decide on the optimal solution.PurposesA new comprehensive evaluation method is proposed to reduce the subjectivity and one-sidedness of the selection process of intelligent escort product design solutions, and to make the decision more objective and reasonable. Such decisions can enhance the experience and naturalness of the elderly using intelligent products.MethodsFirst, a large number of user interviews were analyzed using the grounded theory, gradually refine through theoretical coding, and abstracted with the design scheme evaluation index. Second, the idea of game-theoretic weighting is used to optimize a linear combination of subjective and objective weights to determine the final weights of each evaluation indicator. Finally, the evaluation and selection are completed based on the solution ranking determined by the approximate ideal solution ranking method (TOPSIS). It is applied for the selection of the elderly escort robot design, and the usability test is conducted using the PSSUQ to verify the selection results.ResultsA new comprehensive evaluation method can better complete the preferential selection of product design solutions for healthy aging escorts, and reduce the subjectivity and one-sidedness of the evaluation.ConclusionThis method compensates for the reliance on personal experience in the selection of options, and improve the subjectivity of the evaluation index determination process and the deviation of index weighting. Improving the objectivity and scientificity of decision-making reduces the blindness of design and production. It also provides a theoretical reference for the research scholars of healthy aging companion products.

Pregnancy-related intrahepatic cholestasis (ICP) is a serious complication with adverse perinatal outcomes of preterm labor, fetal distress, or stillbirth. As a result, it is important to investigate and identify the potential critical pathogenic mechanisms of ICP. First, we collected the placental tissues from the ICP with placental weight and fetal birth weight loss for the whole transcriptome sequencing. Then we analyzed the differentially expressed (DE) circRNAs (DEcircRNAs) by SRPBM, DElncRNAs by FRKM, DEmiRNAs by TPM, and DEmRNAs by TPM and RSEM. Based on differential expression of term pregnancy placental tissues from pregnancies impacted by ICP (n=7) as compared to gestational aged matched control tissues (n=5), the circ/lncRNA-miRNA-mRNA competitive endogenous RNA (ceRNA) regulatory networks were constructed. The ceRNA regulatory networks covered 3,714 events, including 21 DEmiRNAs, 36 DEcircRNAs, 146 DElncRNAs, and 169 DEmRNAs. According to the functional analysis, ICP complications were linked to the immune system, signal transduction, endocrine system, cell growth and death, and transport and catabolism. Further evidence suggested that the expression of immune-related genes KLRD1, BRAF, and NFATC4 might have a potential ceRNA mechanism by individual lncRNA sponging miR372-3p, miR-371a-3p, miR-7851-3p, and miR-449a to control downstream the level of TNF-α, IFN-γ, and IL-10, thereby regulating the pathophysiology of ICP. Furthermore, our results were validated by the qRT-PCR, western blotting and ELISA assays. In conclusion, this study is the first to evaluate placental ceRNA networks in pregnancies affected by ICP, showing alterations in immune regulatory networks which may impact fetal and placental growth. Overall our these data suggest that the ceRNA regulatory network may refine biomarker predictions for developing novel therapeutic approaches in ICP.

Tumor metastasis is still an insurmountable obstacle in tumor treatment. Lung cancer represents one of the most common malignancies with high morbidity worldwide. hnRNPA1 has been reported to be involved in the regulation of tumor metastasis, while its specific role in tumor metastasis seems to be controversial and its molecular mechanism in lung cancer metastasis remains to be further elucidated. In this study, we confirmed that knockdown of the hnRNPA1 led to enhanced migration, invasion and EMT transition in lung cancer cells. Bioinformatics analysis of the GSE34992 dataset revealed that hnRNPA1 may regulate the alternative splicing (AS) of LAS1L exon 9. Further AGE assays and RIP assays revealed that hnRNPA1 can directly bind to the LAS1L pre-mRNA to inhibit the splicing of LAS1L exon 9. The RNA pull-down assays showed that hnRNPA1 can specifically bind to the two sites (UAGGGU(WT1) and UGGGGU(WT3)) of LAS1L Intron 9. Further Transwell assays indicated that the expression ratio of LAS1L-L/LAS1L-S regulated by hnRNPA1 can further promote the migration, invasion and EMT transition in lung cancer cells. Moreover, hnRNPA1 expression showed significant heterogeneity in lung cancer tissues, which may contain new research directions and potential therapeutic targets. Our results indicate that hnRNPA1 can affect the metastasis of lung cancer cells by modulating the AS of LAS1L exon 9, highlighting the potential significance of hnRNPA1 in lung cancer metastasis.

BackgroundLimited studies have explored the difference of fatty acid profile between women with and without gestational diabetes mellitus (GDM), and the results were inconsistent. Individual fatty acids tend to be interrelated because of the shared food sources and metabolic pathways. Thus, whether fatty acid patters during pregnancy were related to GDM odds needs further exploration.ObjectiveTo identify plasma fatty acid patters during pregnancy and their associations with odds of GDM.MethodsA hospital-based case-control study including 217 GDM cases and 217 matched controls was carried out in urban Wuhan, China from August 2012 to April 2015. All the participants were enrolled at the time of GDM screening and provided fasting blood samples with informed consent. We measured plasma concentrations of fatty acids by gas chromatography–mass spectrometry, and derived potential fatty acid patterns (FAPs) through principal components analysis. Conditional logistic regression and restricted cubic spline model were used to evaluate the associations between individual fatty acids or FAPs and odds of GDM.ResultsTwenty individual fatty acids with relative concentrations ≥0.05% were included in the analyses. Compared with control group, GDM group had significantly higher concentrations of total fatty acids, 24:1n-9, and relatively lower levels of 14:0, 15:0, 17:0, 18:0, 24:0, 16:1n-7, 20:1n-9,18:3n-6, 20:2n-6, 18:3n-3, 20:3n-3, 22:5n-3. Two novel patterns of fatty acids were identified to be associated with lower odds of GDM: (1) relatively higher odd-chain fatty acids, 14:0, 18:0, 18:3n-3, 20:2n-6, 20:3n-6 and lower 24:1n-9 and 18:2n-6 [adjusted odds ratio (OR) (95% confidence interval) (CI) for quartiles 4 vs. 1: 0.42 (0.23–0.76), P-trend = 0.002], (2) relatively higher n-3 polyunsaturated fatty acids, 24:0, 18:3n-6 and lower 16:0 and 20:4n-6 [adjusted OR (95% CI) for quartiles 4 vs. 1: 0.48 (0.26–0.90), P-trend = 0.018].ConclusionOur findings suggested that two novel FAPs were inversely associated with GDM odds. The combination of circulating fatty acids could be a more significant marker of GDM development than individual fatty acids or their subgroups.

Identifying biomarkers of Multiple Sclerosis is important for the diagnosis and treatment of Multiple Sclerosis. The existing study has shown that miRNA is one of the most important biomarkers for diseases. However, few existing methods are designed for predicting Multiple Sclerosis-related miRNAs. To fill this gap, we proposed a novel computation framework for predicting Multiple Sclerosis-associated miRNAs. The proposed framework uses a network representation model to learn the feature representation of miRNA and uses a deep learning-based model to predict the miRNAs associated with Multiple Sclerosis. The evaluation result shows that the proposed model can predict the miRNAs associated with Multiple Sclerosis precisely. In addition, the proposed model can outperform several existing methods in a large margin.

PurposeTo summarize the technical points and clinical effects of percutaneous balloon compression (PBC) in the treatment of primary trigeminal neuralgia.MethodsThe clinical data of 13 patients with trigeminal neuralgia who received PBC from April 2020 to July 2021 were retrospectively analyzed. VAS, VRS-4 and PPI were used to evaluate the postoperative pain relief. Different postoperative complications were analyzed.ResultsAll patients had a smooth operation, the inflation volume of the balloon was 0.7 ml, the average compression time was 120 s, and there was no balloon rupture during the operation. On the day after operation, 12 patients (92.3%) had complete pain relief, and 1 patient (7.7%) was not satisfied with pain relief, but the pain disappeared 2 weeks after the operation. After operation, there were 12 patients with facial numbness in the affected side (92.3%), 3 patients with masseter muscle weakness (23.0%), 1 patient with herpes around the mouth (7.6%), and 1 patient with diplopia (7.6%).ConclusionPBC is an effective minimally invasive surgical method for the treatment of primary trigeminal neuralgia. It is suitable for the elderly and infirm people, those who cannot tolerate general anesthesia or are afraid of surgery, and patients who had undergone surgery but relapsed after surgery. However, it is necessary to pay attention to the serious facial numbness and postoperative masticatory weakness. These discomforts are generally relieved after half a year.

The global infection rate of fungal diseases is increasing year by year, and it has gradually become one of the most serious infectious diseases threatening human health. However, the side effects of antifungal drugs and the fungal resistance to these drugs are gradually increasing. Therefore, the development of new broad-spectrum, safe, and economical alternatives to antibacterial drugs are essential. Probiotics are microorganisms that are beneficial for human health. They boost human immunity, resist pathogen colonization, and reduce pathogen infection. Many investigations have shown their inhibitory activity on a wide range of pathogenic fungi. However, their antibacterial mechanism is still a secret. This article reviews the progress of probiotics as a new method for the treatment of fungal diseases.

Academic emotions refer to the emotions related to achievement activities or outcomes. Academic emotions are directly related to learning performance and have been recognized as critical to learners’ learning satisfaction and learning effectiveness in the online learning context. This study aimed to explore the relationship between academic emotions and learning satisfaction and their underlying mechanisms in massive open online courses (MOOCs) learning context using mediation models. This study adhered to the theoretical frameworks of the control-value theory (CVT) and the unified theory of acceptance and use of technology (UTAUT). Participants were 283 pre-service teachers who volunteered from a normal university in Southwestern China. Results revealed that: (a) academic emotions did not predict learning satisfaction; (b) learning interest and technology acceptance fully mediated the influence of academic emotions on learning satisfaction; (c) the four dimensions of technology acceptance did not mediate the relationship between academic emotions and learning satisfaction. This study integrated CVT and UTAUT models, and the results emphasized the importance of academic emotions and learning satisfaction in CVT and provision of additional support for UTAUT. Therefore, these findings have significant implications for improving the quality of MOOCs in the post-pandemic era.

IntroductionCandida auris is an emerging multidrug-resistant fungus that may cause infections with a high mortality rate. The first case of C. auris infection was reported in 2009 and infections have been reported in 44 countries. The fungus now represents a major global public health threat. We analyzed cases from the emergence of C. auris infections up until the end of 2020. It is hoped that the results of this analysis will raise awareness in scientists to promote protection and control research pertaining to this pathogen.MethodsPubMed and Web of Science databases were searched for all papers related to C. auris infections up until December 31, 2020. We sorted and organized these data into the following categories: date of publication, patient age and sex, underlying diseases, risk factors for infection, patient mortality information, drug sensitivity information of C. auris isolates, and genetic classification. The χ2 test was used to screen for factors that may affect patient mortality.ResultsA total of 912 patients were included in the analysis. There’s a higher proportion of men and a high proportion of patients were premature babies and elderly people. The proportions of patients with underlying diseases such as diabetes, kidney disease, trauma, and ear disease were also high. More than half of patients had a history of central venous catheter use and a history of broad-spectrum antibiotic use. The χ2 test revealed that only kidney disease (P < 0.05) was an important risk factor for mortality in C. auris-infected patients.ConclusionsA comprehensive understanding of C. auris was achieved following this retrospective analysis, including the characteristics of C. auris-infected patients. In recent years, increasing numbers of multidrug-resistant C. auris isolates have been identified, and the high mortality rates associated with infection merit greater attention from the medical world.

Objective: Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease.Methods: A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (SERPING1, C2, CFB, CFH, C3, and C5) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed.Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls (P = 1.79 × 10−4; odds ratio (OR) 2.18, 95% CI: 1.44–3.29; P = 4.65 × 10−4; OR 3.66, 95% CI: 1.70–7.85, respectively). The additive effect of CFH-rs800292 and SERPING1-rs3824988 was identified with an OR of 12.50 (95% CI: 2.16–72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18–3.53), but the P-value could not withstand the Bonferroni correction (Pcorr > 0.05).Conclusion: This study revealed a genetic association of a CFH variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted.

We previously demonstrated that ureteral obstruction is associated with a urinary concentrating defect and reduced expression of renal aquaporins (AQPs), in which the renin–angiotensin system (RAS) may play an important role. The aims of the present study were to examine whether the renin inhibitor aliskiren could prevent the reduction in AQP expression and improve the urinary concentrating capacity in mice with bilateral ureteral obstruction (BUO) and BUO release. BUO was performed for 24 h, and BUO release was performed for 1 (B-R1D) or 3 days (B-R3D) with or without aliskiren treatment. Aliskiren prevented polyuria and decreased urine osmolality induced by B-R3D. In mice with BUO and BUO release, aliskiren attenuated the reduction in AQP2 protein and mRNA expression in the obstructed kidneys. B-R3D increased the protein expression of NLRP3 inflammasome components ASC, caspase-1, and interleukin-1β in the obstructed kidneys, which was markedly prevented by aliskiren. Moreover, the NF-κB inhibitor Bay 11-7082 blocked NLRP3 inflammasome activation and attenuated the decrease in AQP2 protein expression in primary cultured rat inner medullary collecting duct cells treated with angiotensin II. These results indicate that the renin inhibitor aliskiren increases water channel AQP2 expression at least partially by suppressing NLRP3 inflammasome activation in the obstructed kidneys of mice with BUO and BUO release.

Arginine vasopressin (AVP) mediates water reabsorption in the kidney collecting ducts through regulation of aquaporin-2 (AQP2). Also, estrogen has been known to regulate AQP2. Consistently, we previously demonstrated that tamoxifen (TAM), a selective estrogen receptor modulator, attenuates the downregulation of AQP2 in lithium-induced nephrogenic diabetes insipidus (NDI). In this study, we investigated the AVP-independent regulation of AQP2 by TAM and the therapeutic effect of TAM on the dysregulation of AQP2 and impaired urinary concentration in a unilateral ureteral obstruction (UUO) model. Primary cultured inner medullary collecting duct (IMCD) cells from kidneys of male Sprague-Dawley rats were treated with TAM. Rats subjected to 7 days of UUO were treated with TAM by oral gavage. Changes of intracellular trafficking and expression of AQP2 were evaluated by quantitative PCR, Western blotting, and immunohistochemistry. TAM induced AQP2 protein expression and intracellular trafficking in primary cultured IMCD cells, which were independent of the vasopressin V2 receptor (V2R) and cAMP activation, the critical pathways involved in AVP-stimulated regulation of AQP2. TAM attenuated the downregulation of AQP2 in TGF-β treated IMCD cells and IMCD suspensions prepared from UUO rats. TAM administration in vivo attenuated the downregulation of AQP2, associated with an improvement of urinary concentration in UUO rats. In addition, TAM increased CaMKII expression, suggesting that calmodulin signaling pathway is likely to be involved in the TAM-mediated AQP2 regulation. In conclusion, TAM is involved in AQP2 regulation in a vasopressin-independent manner and improves urinary concentration by attenuating the downregulation of AQP2 and maintaining intracellular trafficking in UUO.

Purpose: Transforming growth factor β (TGFβ) is upregulated in many types of tumors and plays important roles in tumor microenvironment construction, immune escape, invasion, and metastasis. The therapeutic effect of antibodies and nuclide-conjugated drugs targeting TGFβ has not been ideal. Targeting TGFβ with small-molecule or peptide carriers labeled with diagnostic/therapeutic nuclides is a new development direction. This study aimed to explore and confirm the imaging diagnostic efficiency of TGFβ-targeting peptide P144 coupled with [6868le activity was prepared through peptide synthesis and screening, and P144 was coupled with biological chelator DOTA and labeled with radionuclide [68Ga] to achieve a stable TGFβ-targeting tracer [68Ga]Ga-P144. This tracer was first used for positron emission tomography (PET) molecular imaging study of pancreatic cancer in a mouse PANC-1 tumor model. Results: [68Ga]Ga-P144 had a high targeted uptake and relatively long uptake retention time in tumors and lower uptakes in non-target organs and backgrounds. Target pre-blocking experiment with the cold drug P144-DOTA demonstrated that the radioactive uptake with [68Ga]Ga-P144 PET in vivo, especially in tumor tissue, had a high TGFβ-targeting specificity. [68Ga]Ga- P144 PET had ideal imaging efficiency in PANC-1 tumor-bearing mice, with high specificity in vivo and good tumor-targeting effect. Conclusion: [68Ga]Ga-P144 has relatively high specificity and tumor-targeted uptake and may be developed as a promising diagnostic tool for TGFβ-positive malignancies. [ABSTRACT FROM AUTHOR]

Background: Previous experimental studies have shown that mice overexpressing amyloid precursor protein, in which b-amyloid (Ab) is overproduced, exhibit peripheral insulin resistance, pancreatic impairment, and hyperglycemia. We aimed to explore the effects of Ab on insulin action and insulin secretion in vitro and the association of plasma Ab with prediabetes in human. Methods: We examined the effects of Ab40 and Ab42 on insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and insulin secretion in INS-1 cells. Furthermore, we conducted a case-control study (N = 1142) and a nested case-control study (N = 300) within the prospective Tongji-Ezhou cohort. Odds ratios (ORs) and 95% confidence intervals (CIs) for prediabetes were estimated by using conditional logistic regression analyses. Results: In the in vitro studies, Ab40 and Ab42 dose-dependently attenuated insulin-inhibited glucose production in HepG2 cells, insulin-promoted glucose uptake in C2C12 myotubes, and basal and glucose-stimulated insulin secretion in INS-1 cells. In the case-control study, plasma Ab40 (adjusted OR: 2.00; 95% CI: 1.34, 3.01) and Ab42 (adjusted OR: 1.94; 95% CI: 1.33, 2.83) were positively associated with prediabetes risk when comparing the extreme quartiles. In the nested case-control study, compared to the lowest quartile, the highest quartile of plasma Ab40 and Ab42 were associated with 3.51-fold (95% CI: 1.61, 7.62) and 2.75-fold (95% CI: 1.21, 6.22) greater odds of prediabetes, respectively. Conclusion: Elevated plasma Ab40 and Ab42 levels were associated with increased risk of prediabetes in human subjects, which may be through impairing insulin sensitivity in hepatocytes and myotubes and insulin secretion in pancreatic b-cells. [ABSTRACT FROM AUTHOR]

BackgroundSome patients with psoriasis experience relapses shortly after discontinuation of biologics. However, there is a lack of risk prediction tools to identify those at high risk of relapse.ObjectiveTo develop and validate a risk prediction model for psoriasis relapse after biologics discontinuation.MethodsPublications from PubMed, EMBASE, Medline, and the Cochrane Library were systematically searched and meta-analyses were conducted to identify risk factors for psoriasis relapse after biologics discontinuation. Statistically significant risk factors were identified and used to create a risk assessment model weighted by the impact of each factor. The model was externally validated using a cohort of 416 Chinese psoriasis patients.ResultsEight studies (N = 2066) were included in the meta-analysis. Body mass index (BMI), smoking, disease duration, comorbid psoriatic arthritis (PsA), remission speed and extent during treatment, history of biologic therapy, and therapy duration were identified as correlates of relapse in the meta-analysis and were incorporated into the prediction model. The median age of the 416 patients in the validation cohort was 41.5 (IQR 32, 53) years, with 63% male, and a baseline PASI score of 15.4 (IQR 10.5, 21). It was verified that the area under the curve (AUC) of the prediction model was 0.796 (95% CI, 0.753–0.839), with an optimal cut-off value of 11.25 points, sensitivity of 65.1%, and specificity of 82.2%.ConclusionMultivariate models using available clinical parameters can predict relapse risk in psoriasis patients after biologics discontinuation. Early individual identification of patients at risk of relapse, and screening of candidate cohorts for long-term treatment or dose reduction may benefit both patients and physicians.

ObjectiveThis study aims to evaluate the nutritional status of Chinese gynecologic cancer survivors with post-surgical lower limb lymphedema (LLL) by analyzing serum albumin levels and the prognostic nutritional index (PNI).MethodsA retrospective cross-sectional study was conducted at two Chinese medical centers. The cohort comprised 155 gynecologic cancer survivors who developed symptomatic unilateral LLL post-surgery, during the period from September 2021 to June 2024. Nutritional status was assessed by measuring serum albumin and PNI. Statistical analysis was performed using univariate and multivariate logistic regression models to identify factors associated with low serum albumin and PNI.ResultsThe mean age of the cohort was 55.47 ± 10.56 years, and the median total survival time was 72.0 months (36.5, 111.5 months). The prevalence of low serum albumin (< 40 g/L) was 40.0%, and low PNI (< 45) was 80.6%. Significant associations were found between low hemoglobin levels and both low serum albumin (OR = 1.05, 95% CI: 1.02–1.08, p < 0.001) and low PNI (OR = 1.09, 95% CI: 1.04–1.13, p < 0.001). Advanced International Society of Lymphology stage 3 was also associated with low albumin (OR = 0.18, 95% CI: 0.03–0.99, p < 0.05).ConclusionThe study highlights a significant prevalence of high risk of malnutrition among Chinese gynecologic cancer survivors with LLL, underscoring the need for regular nutritional assessments and interventions.

IntroductionThe co-existence of S. mutans and C. albicans is frequently detected in root caries and early child caries and is reported to be associated with recurrent caries. The aim of this study was to investigate the effects of potassium iodide (KI) in combination with toluidine blue O-mediated antimicrobial photodynamic therapy (aPDT) on S. mutans and C. albicans mixed-species biofilm, as well as the antibiofilm mechanisms involved.MethodsMixed-species biofilm was constructed of S. mutans and C. albicans on dentin blocks. The antibiofilm efficacy, cytotoxicity and antibiofilm mechanism of KI in combination with aPDT were determined and evaluated.ResultsKI+TBO-aPDT treatment caused reduction in microorganism counts, metabolic activity, and biofilm biomass of mixed-species biofilm without inducing cytotoxicity to hDPCs (human dental pulp cells). Observations such increased ROS (reactive oxygen species) levels, impaired cell membrane function, cell apoptosis and reduced expression in several genes seem to be artifacts of reduced growth and general killing by KI+TBO-aPDT treatment.DiscussionThese data suggested that KI in combination with aPDT as an innovative approach to combat S. mutans and C. albicans biofilm, and thus as an optional treatment for caries.

BackgroundBoth frailty and elevated serum neurofilament light chain (sNfL) levels are linked to cognitive impairment. However, evidence of their relationship is lacking, and whether it was mediated by renal function was unknown. This study aimed to investigate the association between frailty and sNfL levels in a representative U.S. population, and to explore the potential mediating role of estimated glomerular filtration rate (eGFR) in this relationship.MethodsData from 1,782 participants aged 20–75 years in the 2013–2014 National Health and Nutrition Examination Survey (NHANES) were analyzed. Frailty was assessed using a 49-item frailty index, and participants were categorized as non-frail, pre-frail, or frail. sNfL levels were measured using acoustic emission technology. Multivariable linear regression models and restricted cubic spline analyses were employed to examine the associations between frailty, eGFR, and sNfL levels. Mediation analysis was conducted to evaluate the role of eGFR in the frailty-sNfL relationship.ResultsThe prevalence of pre-frailty and frailty was 45.39 and 11.60%, respectively. A significant positive association was observed between frailty score and sNfL levels (adjusted β: 39.97, SE: 11.07, p = 0.003), with a linear relationship confirmed by restricted cubic spline analysis. Frail individuals had significantly higher sNfL levels compared to non-frail participants (adjusted β: 11.86, SE: 5.42, p = 0.04). eGFR was negatively associated with sNfL levels (adjusted β: -0.23, SE: 0.05, p

BackgroundSleep disorders have emerged as a major public health concern. Observational research indicates that antioxidants might mitigate the risk of sleep disturbances, yet the causal relationship remains uncertain.Materials and methodsThis study utilized data from the National Health and Nutrition Examination Survey (NHANES) spanning 2007 to 2018, focusing on adults who reported sleep disorders. The analysis included 25,178 American adults. We examined the association between the Composite Dietary Antioxidant Index (CDAI) and the prevalence of sleep disorders. Additionally, a two-sample Mendelian randomization analysis was conducted to explore the potential causal link between CDAI and the risk of sleep disorders.ResultsAnalysis of data from the 2007–2018 NHANES survey revealed a significant negative association between CDAI and sleep disorders (OR = 0.854, 95% CI 0.821–0.888, P < 0.001). A multivariable logistic regression model showed that each unit increase in CDAI corresponded to a 14.6% reduction in sleep disorder risk, exhibiting a nonlinear trend where the risk decreased until reaching the inflection point of −0.134. Additionally, MR analysis demonstrated that genetically determined selenium reduces the risk of OSA (OR = 0.992, 95% CI 0.860–0.989, P = 0.023). Furthermore, vitamin E (γ-tocopherol) and vitamin C were protective against sleep-wake disorders (OR = 0.016, 95% CI 0.001–0.674, P = 0.03) and (OR = 0.049, 95% CI 0.007–0.346, P = 0.002), respectively.ConclusionDietary antioxidants may help prevent sleep disorders. However, further studies are required to clarify the pathways through which antioxidants exert this protective effect.

Purpose: The aim of this study was to established a dynamic nomogram for assessing the risk of bone metastasis in patients with thyroid cancer (TC) and assist physicians to make accurate clinical decisions. Methods: The clinical data of patients with TC admitted to the First Affiliated hospital of Nanchang University from January 2006 to November 2016 were included in this study. Demographic and clinicopathological parameters of all patients at primary diagnosis were analyzed. Univariate and multivariate logistic regression analysis was applied to build a predictive model incorporating parameters. The discrimination, calibration, and clinical usefulness of the nomogram were evaluated using the Cindex, ROC curve, calibration plot, and decision curve analysis. Internal validation was evaluated using the bootstrapping method. Results: A total of 565 patients were enrolled in this study, of whom 25 (4.21%) developed bone metastases. Based on logistic regression analysis, age (OR=1.040, P=0.019), hemoglobin (HB) (OR=0.947, P<0.001) and alkaline phosphatase (ALP) (OR=1.006, P=0.002) levels were used to construct the nomogram. The model exhibited good discrimination, with a C-index of 0.825 and good calibration. A C-index value of 0.815 was achieved on interval validation analysis. Decision curve analysis showed that the nomogram was clinically useful when intervention was decided at a bone metastases possibility threshold of 1%. Conclusions: This dynamic nomogram, with relatively good accuracy, incorporating age, HB, and ALP, could be conveniently used to facilitate the prediction of bone metastasis risk in patients with TC. [ABSTRACT FROM AUTHOR]

BackgroundAlthough numerous studies had revealed associations between autoimmune diseases (AIDs) and thyroid cancer (TC), the potential causal associations between the two remain poorly defined.MethodsUsing five approaches, two-sample Mendelian randomization (MR) analyses were carried out to determine the causal effects of 12 major AIDs on risk of TC. The sensitivity analyses were conducted to verify the reliability of the analysis. The reverse MR analysis was performed to evaluate the possibility of reverse causation.ResultsThe results showed a significant causal association of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) on the risk of TC. Genetically predicted PBC elevated the risk of TC (OR = 1.46, 95% CI = 1.06-2.02, p = 0.021). The risk of TC was also increased by genetically predicted SLE (OR = 6.52, 95% CI = 1.38-30.84, p = 0.018) with heterogeneity. After outlier-corrected analyses, the results still suggested that genetically predicted SLE increased the risk of TC (p = 0.019). No evidence of a causal relationship between the remaining 10 AIDs and TC was observed. No reverse causal effects of TC on AIDs were found in reverse MR analysis.ConclusionThese findings support a significant causal association of SLE/PBC on the increased risk of TC, indicating that patients with SLE/PBC should be under a close monitoring of TC.

BackgroundModern radiotherapy exemplified by intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT), has transformed esophageal cancer treatment. Facing challenges in treating thoracic esophageal cancer near vital organs, this study introduces a regression model-based decision support tool for the optimal selection of radiotherapy techniques.MethodsWe enrolled 106 patients diagnosed with locally advanced thoracic esophageal cancer in this study and designed individualized IMRT and VMAT radiotherapy plans for each patient. Detailed dosimetric analysis was performed to evaluate the differences in dose distribution between the two radiotherapy techniques across various thoracic regions. Single-factor and multifactorial logistic regression analyses were employed to establish predictive models (P1 and P2) and factors such as TLV/PTV ratio. These models were used to predict the compliance and potential advantages of IMRT and VMAT plans. External validation was performed in a validation group of 30 patients.ResultsUsing predictive models, we developed a data-driven decision support tool. For upper thoracic cases, VMAT plans were recommended; for middle/lower thoracic cases, the tool guided VMAT/IMRT choices based on TLV/PTV ratio. Models P1 and P2 assessed IMRT and VMAT compliance. In validation, the tool showed high specificity (90.91%) and sensitivity (78.95%), differentiating IMRT and VMAT plans. Balanced performance in compliance assessment demonstrated tool reliability.ConclusionIn summary, our regression model-based decision support tool provides practical guidance for selecting optimal radiotherapy techniques for thoracic esophageal cancer patients. Despite a limited sample size, the tool demonstrates potential clinical benefits, alleviating manual planning burdens and ensuring precise, individualized treatment decisions for patients.

Senecavirus A (SVA) is an emerging virus that belongs to the genus Senecavirus in the family Picornaviridae. Its genome is a positive-sense and single-stranded RNA, containing two untranslated regions (UTRs). The 68-nt-long 3′ UTR is computationally predicted to possess two higher-order RNA structures: a kissing-loop interaction and an H-type-like pseudoknot, both of which, however, cannot coexist in the 3′ UTR. In this study, we constructed 17 full-length SVA cDNA clones (cD-1 to -17): the cD-1 to -7 contained different point mutations in a kissing-loop-forming motif (KLFM); the cD-8 to -17 harbored one single or multiple point mutations in a pseudoknot-forming motif (PFM). These 17 mutated cDNA clones were independently transfected into BSR-T7/5 cells for rescuing recombinant SVAs (rSVAs), named rSVA-1 to −17, corresponding to cD-1 to −17. The results showed that the rSVA-1, -2, -3, -4, -5, -6, -7, -9, -13, and -15 were successfully rescued from their individual cDNA clones. Moreover, all mutated motifs were genetically stable during 10 viral passages in vitro. This study unveiled viral abilities of tolerating mutations in the computationally predicted KLFM or PFMs. It can be concluded that the putative kissing-loop structure, even if present in the 3′ UTR, is unnecessary for SVA replication. Alternatively, if the pseudoknot formation potentially occurs in the 3′ UTR, its deformation would have a lethal effect on SVA propagation. [ABSTRACT FROM AUTHOR]

Epithelioid hemangioendothelioma is a rare vascular malignancy, and currently, there is no standard treatment regimen for this disease and existing treatment options have limited efficacy. In this case report, we present a patient with lung and lymph node metastases from prostate epithelioid hemangioendothelioma who achieved a significant partial response. This was accomplished through alternating nivolumab therapy with ipilimumab and liposomal doxorubicin, resulting in a progression-free-survival more than 6 months to date. The treatment was well-tolerated throughout. Our report suggests that dual immunotherapy alternating with anti-PD-1antibody plus doxorubicin may be a potential treatment modality for epithelioid hemangioendothelioma. However, larger sample studies are necessary to ascertain the effectiveness of this treatment strategy and it is essential to continue monitoring this patient to sustain progression-free survival and overall survival.

BackgroundIt has been reported that tumor immune microenvironment performs a vital role in tumor progress. However, acting mechanism of immune cell related genes (IRGs) in esophageal squamous cell carcinoma (ESCC) is uncertain.MethodsTCGA-ESCC, GSE23400, GSE26886, GSE75241, and GSE196756 datasets were gained via public databases. First, differentially expressed genes (DEGs) between ESCC and control samples from GSE23400, GSE26886, and GSE75241 were screened out by differential expression analysis, and overlapping DEGs were identified. Single-cell transcriptome data of GSE196756 were applied to explore immune cells that might be involved in regulation of ESCC. Then, weighted gene co-expression network analysis was applied to screen IRGs. Next, differentially expressed IRGs (DE-IRGs) were identified by overlapping IRGs and DEGs, and were incorporated into univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox to acquire prognosis-related genes, and ESCC samples were grouped into high-/low-risk groups on the basis of median risk score. Finally, the role of prognosis model in immunotherapy was analyzed.ResultsTotally 248 DEGs were yielded by overlapping 3,915 DEGs in GSE26886, 459 DEGs in GSE23400, and 1,641 DEGs in GSE75241. Single-cell analysis found that B cells, dendritic cells, monocytes, neutrophils, natural killer cells, and T cells were involved in ESCC development. Besides, MEred, MEblack, MEpink, MEblue and MEbrown modules were considered as key modules because of their highest correlations with immune cell subtypes. A total of 154 DE-IRGs were yielded by taking intersection of DEGs and genes in key modules. Moreover, CTSC, ALOX12, and RMND5B were identified as prognosis-related genes in ESCC. Obviously, Exclusion and TIDE scores were notably lower in high-risk group than in the other one, indicating that high-risk group was more responsive to immunotherapy.ConclusionsThrough bioinformatic analysis, we identified a prognosis model consisting of IRGs (CTSC, ALOX12, and RMND5B) in ESCC, providing new ideas for studies related to treatment and prognosis of ESCC.

BackgroundThe extra-articular lesions of rheumatoid arthritis (RA) are reported to involve multiple organs and systems throughout the body, including the heart, kidneys, liver, and lungs. This study assessed the potential causal relationship between RA and the risk of chronic kidney diseases (CKDs) using the Mendelian randomization (MR) analysis.MethodIndependent genetic instruments related to RA and CKD or CKD subtypes at the genome-wide significant level were chosen from the publicly shared summary-level data of genome-wide association studies (GWAS). Then, we obtained some single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs), which are associated with RA in individuals of European origin, and had genome-wide statistical significance (p5 × 10−8). The inverse-variance weighted (IVW) method was the main analysis method in MR analysis. The other methods, such as weighted median, MR–Egger, simple mode, and weighted mode were used as supplementary sensitivity analyses. Furthermore, the levels of pleiotropy and heterogeneity were assessed using Cochran’s Q test and leave-one-out analysis. Furthermore, the relevant datasets were obtained from the Open GWAS database.ResultsUsing the IVW method, the main method in MR analysis, the results showed that genetically determined RA was associated with higher risks of CKD [odds ratio (OR): 1.22, 95% confidence interval (CI) 1.13–1.31; p

Canine distemper and canine parvoviral enteritis are infections caused by the canine distemper virus (CDV) and canine parvovirus type 2 (CPV-2), respectively. They are two common infectious diseases that cause high morbidity and mortality in affected dogs. Combination vaccines have been broadly used to protect dogs from infections of CDV, CPV-2, and other viruses. VP2 is the most abundant protein of the CPV-2 capsid. It elicits potent immunity in animals and, therefore, is widely used for designing subunit antigen-based vaccines. In this study, we rescued a recombinant CDV (QN vaccine strain) using reverse genetics. The recombinant CDV (rCDV-VP2) was demonstrated to express stably the VP2 in cells for at least 33 serial passages in vitro. Unfortunately, a nonsense mutation was initially identified in the VP2 open reading frame (ORF) at passage-34 (P34) and gradually became predominant in rCDV-VP2 quasispecies with passaging. Neither test strip detection nor indirect immunofluorescence assay demonstrated the expression of the VP2 at P50. The P50 rCDV-VP2 was subjected to next-generation sequencing, which totally identified 17 single-nucleotide variations (SNVs), consisting of 11 transitions and 6 transversions. Out of the 17 SNVs, 1 and 9 were identified as nonsense and missense mutations, respectively. Since the nonsense mutation arose in the VP2 ORF as early as P34, an earlier rCDV-VP2 progeny should be selected for the vaccination of animals in future experiments. [ABSTRACT FROM AUTHOR]

The name porcine reproductive and respiratory syndrome virus (PRRSV) NADC30-like was first coined in 2015. It originated from the NADC30 strain that was introduced into China by importing breeding pigs and has since undergone mutations or recombination, resulting in variant viruses. Following widespread outbreaks in China in recent years, these NADC30-like strains have presented major health challenges in swine production systems. Outcomes induced by PRRSV NADC30-like infection are highly variable, ranging from inapparent to severe, depending on the recombination between NADC30 and field PRRSV strains prevalent in swine farms. Vaccines and strict biosecurity measures have been explored to fight this disease; however, current PRRSV commercially modified-live virus vaccines (MLVs) have the potential to revert to virulence and only provide limited or no cross-protection efficacy against NADC30-like strains. PRRSVs will remain an ongoing challenge to the swine industry until safe and effective vaccines or antiviral reagents are developed. [ABSTRACT FROM AUTHOR]

IntroductionPlacental syndromes, which include pregnancy loss, preterm birth, gestational diabetes mellitus (GDM), and hypertensive disorders in pregnancy (HDP), have a strong association with disorder inflammatory reactions. Nonetheless, the exact causal relationship has not been established. This study aims to investigate the causal relationship between placental syndromes and inflammatory cytokines utilizing Mendelian randomization (MR). Additionally, we examined the interaction between small molecular compounds derived from traditional Chinese medicine and inflammatory cytokines using molecular docking method.MethodsAfter obtaining the data of inflammatory cytokines and placental syndromes, as well as establishing single nucleotide polymorphisms (SNPs), we employed the inverse variance weighted (IVW) method to assess the causal relationship. We also accessed the heterogeneity and the horizontal pleiotropy of these data. The “ClusterProfiler” R package was utilized for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term analyses. The protein-protein interaction (PPI) network was constructed using STRING database. AutoDock Vina software was used for molecular docking, and Discovery Studio 2019 was used for visualization purposes.ResultsWe found that the growth regulated oncogene A (GROA) and interleukin-9 (IL-9) were associated with the development of pregnancy hypertension, whereas interleukin-10 (IL-10) and hepatocyte growth factor (HGF) were linked to the occurrence of preeclampsia. Moreover, there were correlations observed between interleukin-18 (IL-18), IL-10, macrophage colony-stimulating factor (MCSF), and platelet-derived growth factor BB (PDGFbb) in cases of chronic hypertension combined with pregnancy (CHP). Additionally, macrophage migration inhibitory factor (MIF) exhibited a connection with GDM, and TNF related apoptosis inducing ligand (TRAIL) demonstrated a causal relationship with preterm birth. It is plausible to suggest that interleukin-1β (IL-1β) might contribute to the promotion of pregnancy loss. All of the binding free energy values of small molecular compounds with inflammatory cytokines were below −5.0 kcal/mol. Furthermore, all of the RMSD values were less than 2.ConclusionsGROA, IL-1β, IL-9, IL-10, IL-18, MIF, MCSF, HGF, PDGFbb and TRAIL were found to be causally associated with placental syndromes. Molecular docking analysis revealed that small molecular compounds, such as puerarin, magnolol, atractylenolide I, paeoniflorin, tumulosic acid and wogonin, are closely bound to these inflammatory cytokines.

Introduction:LMNA splicing mutations occur in 9.1% of cases with cardiac involvement cases, but the phenotype and severity of disease they cause have not yet been systematically studied. The aim of this study was to understand the clinical and pathogenic characteristics of the LMNA splice-site mutation phenotype in patients with LMNA-related dilated cardiomyopathy (DCM) and sudden cardiac death (SCD).Methods and Results: First, we reported a novel family with LMNA-related DCM and SCD, and the clinical characteristics of all current patients with LMNA splicing mutations were further summarized through the ClinVar database. Seventeen families with a total of 134 individuals, containing a total of 15 LMNA splicing mutation sites, were enrolled. A total of 42 subjects (31.3%) had SCD. Compared without with the non-DCM group (n = 56), the patients within the DCM group (n = 78) presented a lower incidence of atrioventricular block (AVB) (p = 0.015) and a higher incidence rates of non-sustained ventricular tachycardia (p = 0.004),) and implantable cardioverter defibrillator (ICD) implantation (p = 0.005). Kaplan‒Meier survival analysis showed that the patients with pacemaker (PM) implantation had a significantly reduced the occurrence of SCD compared to patientswith those without PM implantation (log-rank p < 0.001), while there was no significant difference in ICD implantation between the two groups (log-rank p = 0.73). Second, we identified the family that we reported with a mutation in an LMNA c.513+1 G>A mutation in the reported family, and pathogenic prediction analysis showed that the mutation site was extremely harmful. Next, we conducted gene expression levels and cardiac pathological biopsy studies on the proband of this family. We found that the expression of normal LMNA mRNA from the proband was significantly downregulated in peripheral blood mononuclear cells than incompared with healthy individuals. Finally, we comprehensively summarized the pathological characteristics of LMNA-related DCM, including hypertrophy, atrophy, fibrosis, white blood cell infiltration, intercalated disc remodeling, and downregulation of desmin and connexin 43 (Cx43) expression.Discussion: Above all, Cardiaccardiac involvement in patients with LMNA splice-site mutation presented with a high rate of SCD. Implanting a pacemaker significantly reduced the SCD rate in non-DCM patients with AVB. The pathogenic characterization was not only haveinvolved suppressed the expression of the healthy LMNA allele, but was also associated with abnormal expression and distribution of desmin and Cx43.

In the Changning block of the southern Sichuan Basin, the shale gas wells in the Upper Ordovician Wufeng Formation to Lower Silurian Longmaxi Formation (Wufeng–Longmaxi) demonstrate significant difference in flowback rate of fracturing fluid, given the same fracturing scale and production time. Based on the P90 curve of flowback rate with time, wells with high flowback rates in this area are categorized, and they are generally defined with the 100-day flowback rate of >40%, the 200-day flowback rate of >50%, and the first-year flowback rate >60%. Through comprehensive research on the geological characteristics of the Changning block, the geological factors that cause high gas well backflow rates have been identified. The results are obtained in four aspects. First, gas wells with high flowback rates generally show higher flow rates for smaller distances to the fault, and the NE faults formed during the late Yanshanian to early Himalayan and with fault throw >200 m have the greatest impact on the flowback rate. Second, plane heterogeneity of water saturation contributes to the high flowback rate of some wells. Third, the proportion of the Middle Ordovician Baota Formation in the horizontal section of wells is positively related to the flowback rate, and the drilling and fracturing of the Baota limestone with high water content can lead to high flowback rates of gas wells to some extent. Fourth, unidirectional linear natural fractures between wells can easily cause inter-well frac-hit, leading to high flowback rates of gas wells. In conclusion, the research results are helpful in predicting areas where high backflow rate gas wells may occur and developing corresponding drainage and production methods in advance.

Due to lacking a proofreading mechanism in their RNA-dependent RNA polymerases (RdRp), RNA viruses generally possess high mutation frequencies, making them evolve rapidly to form viral quasispecies during serial passages in cells, especially treated with mutagens, like ribavirin. Canine distemper virus (CDV) belongs to the genus Morbillivirus. Its L protein functions as an RdRp during viral replication. In this study, a recombinant enhanced green fluorescence protein-tagged CDV (rCDV-eGFP) was rescued from its cDNA clone, followed by viral identification and characterization at passage-7 (P7). This recombinant was independently subjected to extra 40 serial passages (P8 to 47) in ribavirin- and non-treated cells. Two viral progenies, undergoing passages in ribavirin- and non-treated VDS cells, were named rCDV-eGFP-R and -N, respectively. Both progenies were simultaneously subjected to next-generation sequencing (NGS) at P47 for comparing their quasispecies diversities with each other. The rCDV-eGFP-R and -N showed 62 and 23 single-nucleotide mutations (SNMs) in individual antigenomes, respectively, suggesting that the ribavirin conferred a mutagenic effect on the rCDV-eGFP-R. The spectrum of 62 SNMs contained 26 missense and 36 silent mutations, and that of 23 SNMs was composed of 17 missense and 6 silent mutations. Neither the rCDV-eGFP-R nor -N exhibited nonsense mutation in individual antigenomes. We speculate that the rCDV-eGFP-R may contain at least one P47 sub-progeny characterized by high-fidelity replication in cells. If such a sub-progeny can be purified from the mutant swarm, its L protein would elucidate a molecular mechanism of CDV high-fidelity replication. [ABSTRACT FROM AUTHOR]

Objective: Posner-Schlossman syndrome (PSS), also known as glaucomatocyclitic crisis, is an ocular condition characterized by recurrent attacks of anterior uveitis and raised intraocular pressure. Previous studies by our team and others have identified the genetic association of complement pathway genes with uveitis and glaucoma. This study aimed to investigate the complement genes in PSS patients with the view of elucidating the genetic background of the disease. Methods: A total of 331 subjects (56 PSS patients and 275 controls) were recruited for this study. We selected 27 variants in six complement pathway genes (SERPING1, C2, CFB, CFH, C3 , and C5) and detected them using TaqMan single nucleotide polymorphism (SNP) Genotyping Assays. Univariate SNP association analysis, haplotype-based association analysis, gene-gene interaction analysis among complement genes, and genotype-phenotype correlation analysis were performed. Results: Among the 27 variants of six complement pathway genes, the functional variant I62V (rs800292) at the CFH gene was found to be significantly associated with PSS; there was a significant increase in the frequency of A allele and AA homozygosity in PSS patients than in controls (P = 1.79 × 10−4; odds ratio (OR) 2.18, 95% CI: 1.44–3.29; P = 4.65 × 10−4; OR 3.66, 95% CI: 1.70–7.85, respectively). The additive effect of CFH -rs800292 and SERPING1 -rs3824988 was identified with an OR of 12.50 (95% CI: 2.16–72.28). Genotype-phenotype analysis indicated that the rs800292 AA genotype was associated with a higher intraocular pressure and higher frequency of recurrence. Unlike a high proportion of human leukocyte antigen (HLA)-B27 positivity in anterior uveitis, only 3 in 56 (5.36%) PSS patients were HLA-B27 positive. In addition, one haplotype block (GC) in the SERPING1 gene showed a nominal association with PSS with an increased risk of 2.04 (P = 0.01; 95% CI: 1.18–3.53), but the P -value could not withstand the Bonferroni correction (P corr > 0.05). Conclusion: This study revealed a genetic association of a CFH variant with PSS as well as its clinical parameters, implying that the alternative complement pathway might play an important role in the pathogenesis of PSS. Further studies to enrich the understanding of the genetic background of PSS and the role of the complement system in ocular inflammation are warranted. [ABSTRACT FROM AUTHOR]

ObjectiveSince 2022, Omicron has been circulating in China as a major variant of the novel coronavirus, but the effects of infection with Omicron variants on pregnant women and newborns are unknown. The purpose of this study was to determine the clinical characteristics of Omicron infection during pregnancy and its effect on pregnancy outcomes.MethodsThis study retrospectively analyzed the data of 93 confirmed cases of novel coronavirus infection and 109 non-infected patients admitted to the isolation ward of Guangdong Maternal and Child Health Hospital from December 1, 2022 to January 31, 2023, and statistically analyzed the clinical features of Omicron variant infection during pregnancy and its impact on pregnancy outcomes. Further effects of underlying diseases on Omicron infection in pregnant women were analyzed.ResultsThe incubation period of COVID-19 infection was 0.99±0.86 days, 94.38% of patients had fever or other respiratory symptoms, the lymphocyte count in the infected group was lower than that in the uninfected group, and the lymphocyte count was further reduced in the patients with pregnancy complications or complications. Compared with the uninfected group, APTT and PT were prolonged, platelet count and fibrinogen were decreased in the infected group, all of which had statistical significance. COVID-19 infection during pregnancy increased the rate of cesarean section compared to uninfected pregnant patients, and COVID-19 infection in gestational diabetes resulted in a 4.19-fold increase in cesarean section rate. There was no statistically significant difference in gestational age between the two groups. The incidence of intrauterine distress, turbidity of amniotic fluid and neonatal respiratory distress were higher in the infection group. No positive cases of neonatal COVID-19 infection have been found.ConclusionThe patients infected with omicron during pregnancy often have febrile respiratory symptoms with lymphocyopenia, but the incidence of severe disease is low. Both Omicron infection and gestational diabetes further increase the incidence of cesarean section, and this study found no evidence of vertical transmission of Omicron.

To understand the occurrence state of fracturing fluid in shale gas matrix-fracture system, an experimental method for evaluating fracturing fluid flow characteristics in matrix-fracture system was established. By using Nuclear Magnetic Resonance method, the flow characteristics of fracturing fluid were investigated from three processes of filtration, well shut-in and flowback. The T2 spectrum of fracturing fluid flow process and fracturing fluid saturation in matrix-fracture core model were clarified. The results demonstrate that the peak area of T2 spectra increases gradually during the filtration process, and the fracturing fluid quickly fills the fractures and matrix pores. During the well shut-in process, the fracturing fluid gradually flows from the fracture space to the matrix pores, and the signal of the matrix pores increases by 50.5%. During the flowback process, fracturing fluid flows out of the matrix and fracture. And when it reaches a stable state, the peak signal in the fracture decreases by 64.5% and the matrix signal reduces by 18.8%. The better the porosity and permeability characteristics of the core, the more likely the fracturing fluid is to stay in the formation and cannot be discharged. This paper would contribute to basic parameters for shale gas fracturing design and production strategy optimization.

BackgroundsFrailty is a significant problem for older persons since it is linked to a number of unfavorable consequences. According to observational researches, air pollution may raise the risk of frailty. We investigated the causal association between frailty and air pollution (including PM2.5, PM2.5–10, PM10, nitrogen dioxide, and nitrogen oxides) using Mendelian randomization approach.MethodsWe conducted MR analysis using extensive publically accessible GWAS (genome-wide association studies) summary data. The inverse variance weighted (IVW) method was employed as the primary analysis method. The weighted median model, MR-Egger, simple model, and weighted model approaches were chosen for quality control. The Cochran’s Q test was utilized to evaluate heterogeneity. Pleiotropy is found using the MR-Egger regression test. The MR-PRESSO method was used to recognize outliers. The leave-one-out strategy was used to conduct the sensitivity analysis.ResultsMR results suggested that PM2.5 was statistically significantly associated with frailty [odds ratio (OR) = 1.33; 95%confidence interval (CI) = 1.12–1.58, p = 0.001] in IVW method. We observed no statistical association between PM2.5–10(OR = 1.00, 95% CI = 0.79–1.28, p = 0.979), PM10(OR = 0.91, 95% CI = 0.75–1.11, p = 0.364), nitrogen dioxide (OR = 0.98, 95% CI = 0.85–1.12, p = 0.730), nitrogen oxides (OR = 1.15, 95% CI = 0.98–1.36, p = 0.086) and frailty. There was no pleiotropy in the results. The sensitivity analysis based on the leave-one-out method showed that the individual single nucleotide polymorphisms (SNPs) did not affect the robustness of the results.ConclusionThe current MR investigation shows a causal association between PM2.5 and frailty. Frailty’s detrimental progression may be slowed down with the help of air pollution prevention and control.

IntroductionHypomorphic mutations of DCLRE1C cause an atypical severe combined immunodeficiency (SCID), and Epstein-Barr virus (EBV)-related colon lymphoma is a rare complication.Case presentationA teenage boy presented with colon EBV-related colon lymphoma, plantar warts, and a history of recurrent pneumonia. His peripheral blood lymphocyte count and serum level of immunoglobulin (Ig) G were normal, but he exhibited a T+B-NK+ immunophenotype. Genetic analysis by whole exome sequencing revealed compound heterozygous mutations of DCLRE1C (NM_001033855.3), including a novel paternal splicing donor mutation (c.109 + 2T>C) in intron 1, and a maternal c.1147C>T (p.R383X) nonsense mutation in exon 13. Based on his clinical features and genetic results, the diagnosis of atypical SCID with colon lymphoma was established. Our review shows that seven patients, including our patient, have been reported to develop lymphoma, all with hypomorphic DCLRE1C mutations. Among these cases, six had EBV-related B-cell lineage lymphoma, and one had Hodgkin lymphoma with EBV reactivation. Unfortunately, all of the patients died.ConclusionRecognizing the radiosensitivity of the disease is critical for the prognosis. Hematopoietic stem cell transplantation before being infected with EBV is an optimal treatment.

Excessive nitrogen emissions are a major contributor to water pollution, posing a threat not only to the environment but also to human health. Therefore, achieving deep denitrification of wastewater is of significant importance. Traditional biological denitrification methods have some drawbacks, including long processing times, substantial land requirements, high energy consumption, and high investment and operational costs. In contrast, the novel bio-denitrification technology reduces the traditional processing time and lowers operational and maintenance costs while improving denitrification efficiency. This technology falls within the category of environmentally friendly, low-energy deep denitrification methods. This paper introduces several innovative bio-denitrification technologies and their combinations, conducts a comparative analysis of their denitrification efficiency across various wastewater types, and concludes by outlining the future prospects for the development of these novel bio-denitrification technologies.

BackgroundHeat-clearing and dampness-eliminating Chinese medicine (HDCM) has been studied in clinical trials for cervical HPV infection for decades. However, there has been little comprehensive assessment of the strength and quality of the evidence. Therefore, this study conducted a systematic review and meta-analysis to assess the effectiveness and safety of HDCM in high-risk cervical HPV-infected patients.MethodsThe research focus questions were constructed in accordance with the criteria of participants, intervention, comparison, and outcomes (PICO), and a protocol was registered in PROSPERO. Comprehensive and systematic searches and inquiries in eight electronic databases were conducted from their inception to 30th June 2022. Further, a systematic review and meta-analysis of all randomized controlled trials (RCTs) were conducted to evaluate the HDCM therapy methods.ResultsA total of 12 studies were eligible for inclusion, including 1,574 patients. Data synthesis showed that the HPV clearance rate of HDCM groups was superior to both interferon and follow-up groups (RR = 1.40,95% CI:1.15, 1.71, P < 0.01) and (RR = 3.15, 95% CI:2.43,4.08, P < 0.01), respectively. HDCM was proven to exhibit greater potential in reducing HPV-DNA virus load (MD = −5.16, 95% CI: −5.91, −4.41, P < 0.01). The reversal rate of cervical intraepithelial neoplasia (CIN) for HDCM groups was approximately 2.8 times (RR = 2.80, 95% CI: 2.19, 3.57, P < 0.01), as high as the follow-up groups. Additionally, the recurrence rate of HR-HPV at the end of follow-up in this meta-analysis was reported to be lower in HDCM groups compared to follow-up groups [6.81% (16/235) and 14.65% (29/198), respectively]. The most commonly used Chinese herbal remedies were as follows: Huangbai (Phellodendron chinense var.Glabriusculum C.K. Schneid.), Kushen (Sophora flavescens Aiton), Daqingye (Isatis indigotica Fortune), Zicao (Arnebia hi-spidissima DC.), Baihuasheshecao (Hedyotis diffusa Spreng.), Banlangen (Isatis tinctoria subsp.tinctoria L.), Huzhang (Reynoutria japonica Houtt.), and Huangqi (Orobanche astragali Mouterde).ConclusionHDCM interventions appeared to generate significant effects on enhancing the rate of HR-HPV clearance, reducing the HPV-DNA virus load, and increasing the CIN regression rate. Some active components were confirmed to be responsible for this efficacy, which deserves further exploration.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022333226.

The non-invasive and rapid assessment of the developmental potential of embryos is of great clinical importance in assisted reproductive technology (ART). In this retrospective study, we analyzed the metabolomics of 107 samples provided by volunteers and utilized Raman spectroscopy to detect the substance composition in the discarded culture medium of 53 embryos resulting in successful pregnancies and 54 embryos that did not result in pregnancy after implantation. The culture medium from D3 cleavage-stage embryos was collected after transplantation and a total of 535 (107 × 5) original Raman spectra were obtained. By combining several machine learning methods, we predicted the developmental potential of embryos, and the principal component analysis–convolutional neural network (PCA-CNN) model achieved an accuracy rate of 71.5%. Furthermore, the chemometric algorithm was used to analyze seven amino acid metabolites in the culture medium, and the data showed significant differences in tyrosine, tryptophan, and serine between the pregnancy and non-pregnancy groups. The results suggest that Raman spectroscopy, as a non-invasive and rapid molecular fingerprint detection technology, shows potential for clinical application in assisted reproduction.

IntroductionThe effects of climate warming on starch multi-structure and flour and starch functionality of late-season indica-japonica hybrid rice (IJHR) in double-rice cropping systems are still unclear to date.MethodsA 2 years field warming experiment was conducted by using free-air temperature increase facilities with an IJHR cultivar (Yongyou1538). The starch multi-structure and flour and starch functionality of IJHR were determined.ResultsExperimental warming (on average 2.1°C over the 2 years) reduced the amylose content and increased the amount of short amylopectin branch-chains (degree of polymerization 6–12), possibly due to decreased granule-bound starch synthase activity and increased starch-branch enzyme activity. Additionally, the protein content, starch granule diameter, relative crystallinity, and swelling power of IJHR were enhanced by experimental warming. The changes in rice components and starch multi-structure under warming conditions resulted in high peak viscosity, breakdown, pasting temperature, gelatinization temperatures and enthalpy and low setback of rice starch and high peak viscosity and pasting temperature and low setback of rice flour.ConclusionOur results indicated that climate warming might improve the pasting viscosities and enhance the thermal stability of late-season IJHR.

Only a few case reports in the medical literature describe radiation-induced iliac vein stenosis and endovascular therapy. We present a case of left external iliac vein stenosis resulting from radiotherapy for cervical cancer in which the iliac vein ruptured during the standard iliac vein stenting procedure. The emergency condition was resolved with the implantation of a covered stent and resuscitation with crystalloid and blood transfusion. The patient recovered without additional complications and was discharged eight days after endovascular therapy. At the six-month follow-up, the left lower limb edema had resolved completely, and the deep vein remained patent. This case might raise concerns regarding the potential risk of treating radiation-induced iliac venous stenosis, which may differ from that of a patient without a history of radiation therapy. Iliac vein rupture, iliac vein stenting, radiation-induced venous stenosis, case report

IntroductionClimate warming has pronounced effects on rice production in China. However, late-seasons rice cultivars are diverse in double rice cropping systems, and the actual responses in grain yield and quality of different late-season rice cultivars to climate warming are still unclear.MethodsA two-year field warming experiment was conducted by using free-air temperature increase facilities with three widely-planted late-season rice cultivars, including Taiyou398 (TY, short growth duration indica hybrid rice), Jiuxiangnian (JXN, long growth duration indica inbred rice), and Yongyou1538 (YY, long growth duration indica-japonica hybrid rice) in a double rice cropping system in subtropical China.ResultsWarming (1.9–2.0°C) had no significant effects on the grain yields of TY and JXN, but significantly decreased that of YY by 4.8% relative to ambient treatment due to a reduction of spikelet number. Compared to ambient treatment, the head rice yields of TY and YY did not change while that of JXN increased by 6.3% under warming conditions. Warming significantly increased the head rice rates of JXN and YY by 6.6% and 7.8%, and the chalky grain rates of TY, JXN, and YY by 79.1%, 21.6%, and 7.6%, respectively. Under warming conditions, the amylose content of JXN and YY decreased significantly by 7.5% and 8.8%, and the setback of three cultivars decreased significantly by an average of 41.5%.ConclusionWarming could improve the milling and eating qualities of long growth duration late-season rice (JXN and YY) and increase or maintain their head rice yield, even though decreased the grain yield of indica-japonica hybrid rice (YY). These results will provide a better understanding for the selection of suitable late-season rice cultivars under future climate warming conditions.

Candida albicans (C. albicans) is the most frequent strain associated with cross-kingdom infections in the oral cavity. Clinical evidence shows the co-existence of Streptococcus mutans (S. mutans) and C. albicans in the carious lesions especially in children with early childhood caries (ECC) and demonstrates the close interaction between them. During the interaction, both S. mutans and C. albicans have evolved a complex network of regulatory mechanisms to boost cariogenic virulence and modulate tolerance upon stress changes in the external environment. The intricate relationship and unpredictable consequences pose great therapeutic challenges in clinics, which indicate the demand for de novo emergence of potential antimicrobial therapy with multi-targets or combinatorial therapies. In this article, we present an overview of the clinical significance, and cooperative network of the cross-kingdom interaction between S. mutans and C. albicans. Furthermore, we also summarize the current strategies for targeting cross-kingdom biofilm.

Bipolar androgen therapy (BAT) is a new endocrinologic treatment for castration-resistant prostate cancer (CRPC) that can restore some patients’ sensitivity to drugs such as abiraterone (Abi) and enzalutamide (Enz). We performed a meta-analysis using STATA16. Sensitivity analyses were performed by examining the effects of individual studies using different effect models and detecting any publication bias using the Harbord test. In a total of 108 unique records, ten studies were included in the final meta-analysis. Participants who underwent BAT achieved a PSA50 response rate of 27% (95%CI [0.22,0.31], I2=17.98%), ORR of 34% (95%CI [0.24,0.43], I2=0), and incidence of AEs (grade≥3) of 14% (95%CI [0.09,0.19], I2=0). Patients who completed BAT proceeded to AR-targeted therapy (Abi or Enz) and achieved a PSA50 response rate of 57% (95% CI [0.36,0.78], I2=0). Patients with prior Enz resistance had a stronger impact on the PSA50 of AR-target therapy rechallenge. The results of this meta-analysis indicate that BAT is a safe and effective treatment for patients who have progressed after Abi or Enz. BAT can trigger the resensitization of patients with CRPC to subsequent endocrine therapy and improve the overall survival of patients and their quality of life.