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Background: Citrullinemia type I (CTLN1) is a rare autosomal recessive inborn error of the urea cycle caused by mutations in the gene encoding the arginosuccinate synthetase (ASS1) enzyme. Classic CTLN1 often manifests with acute hyperammonemia and neurological symptoms. Molecular genetic testing is critical for patient diagnosis.Methods: Three unrelated families with clinically suspected CTLN1 were included in this study. Potential pathogenic variants were identified using whole exome sequencing (WES) and validated using Sanger sequencing. Western blotting, quantitative PCR, immunofluorescent staining, and ELISA were used to assess functional changes in candidate ASS1 variants.Results: Five variants were identified, two of which were novel, and one has been reported, but its pathogenicity was not validated. The novel variant c.649-651del (p.P217del) and the 5′UTR variant (c.-4C>T) resulted in a decrease in ASS1 expression at both the protein and transcription levels. The other novel variant, c.1048C>T (p.Q350*), showed a marked decrease in expression at the protein level, with the formation of truncated proteins but an increased transcription. Both c.649_651del (p.P217del) and c.1048C>T (p.Q350*) showed a highly significant reduction in enzyme activity, while c.-4C>T had no effect.Conclusion: We identified two novel variants and a hypomorphic non-coding variant in ASS1 and validated the pathogenicity using functional studies. Our findings contribute to expanding the spectrum of ASS1 variants and understanding the genotype-phenotype relationships of CTLN1.

Chromosomal mosaicism remains a perpetual diagnostic and clinical dilemma. In the present study, we detected two prenatal trisomy 9 mosaic syndrome cases by using multiple genetic testing methods. The non-invasive prenatal testing (NIPT) results suggested trisomy 9 in two fetuses. Karyotype analysis of amniocytes showed a high level (42%–50%) of mosaicism, and chromosomal microarray analysis (CMA) of uncultured amniocytes showed no copy number variation (CNV) except for large fragment loss of heterozygosity. Ultrasound findings were unmarkable except for small for gestational age. In Case 1, further umbilical blood puncture confirmed 22.4% and 34% trisomy 9 mosaicism by CMA and fluorescent in situ hybridization (FISH) respectively. After comprehensive consideration of the genetic and ultrasound results, the two gravidas decided to receive elective termination and molecular investigations of multiple tissue samples from the aborted fetus and the placenta. The results confirmed the presence of true fetoplacental mosaicism with levels of trisomy 9 mosaicism from 76% to normal in various tissues. These two cases highlight the necessity of genetic counseling for gravidas whose NIPT results highly suggest the risk of chromosome 9 to ascertain the occurrence of mosaicism. In addition, the comprehensive use of multiple genetic techniques and biological samples is recommended for prenatal diagnosis to avoid false-negative results. It should also be noted that ultrasound results of organs with true trisomy 9 mosaicism can be free of structural abnormalities during pregnancy.

BackgroundThis study aimed to observe the correlation between renal cortical blood perfusion (CBP) parameters and BP response in patients with severe renal artery stenosis (RAS) who underwent stenting.MethodsThis was a single-center retrospective cohort study. A total of 164 patients with unilateral severe RAS after successful percutaneous transluminal renal artery stenting in Beijing Hospital from October 2017 to December 2020 were included. According to the results of BP evaluated at 12 months, all patients were divided into the BP response group (n = 98) and BP nonresponse group (n = 66). The baseline clinical and imaging characteristics and follow-up data about 24 h ABPM and CBP were recorded and analyzed. Pearson correlation analysis was used to evaluate the relationship between CBP parameters and 24 h average SBP. Univariate and multivariate logistic regression analysis was used to evaluate the risk factors for BP response.ResultsAmong 164 patients with severe RAS, there were 100 males (61.0%), aged 37–75 years, with an average of 56.8 ± 18.4 years, and average artery stenosis of 84.0 ± 12.5%. The BP nonresponse patients had a longer duration of hypertension, more current smoking subjects and diabetic patients, lower eGFR, increased number of hypertensive agents, and rate of insulin compared with the BP response group (P < 0.05). After PTRAS, patients in the BP response group were associated with significantly lower BP and improved CPB, characterized by increased levels of maximum intensity (IMAX), area under ascending curve (AUC1), area under the descending curve (AUC2), shortened rising time (RT), mean transit time (mTT), and prolonged time to peak intensity (TTP; P < 0.05). However, the BP nonresponse group was only associated with significantly reduced RT (P < 0.05) compared with baseline data. During an average follow-up of 11.5 ± 1.7 months, the BP response group was associated with significantly lower levels of SBP, DBP, 24 h average SBP, and 24 h average DBP compared with the nonresponse group (P < 0.05). Pearson correlation analysis showed that the the pre-operative CBP parameters, including IMAX (r = 0.317), RT (r = 0.249), AUC1 (r = 0.614), AUC2 (r = 0.558), and postoperative CBP parameters, including RT (r = 0.283), AUC1 (r = 0.659), and AUC2 (r = 0.674) were significantly positively correlated with the 24 h average SBP, while the postoperative TTP (r = −0.413) and mTT (r = −0.472) were negatively correlated with 24 h average SBP (P < 0.05). Multivariate Logistic regression analysis found that diabetes (OR = 1.294), NT-proBNP (OR = 1.395), number of antihypertensive agents (OR = 2.135), pre-operation IMAX (OR = 1.534), post-operation AUC2 (OR = 2.417), and baseline dDBP (OR = 2.038) were related factors for BP response (all P < 0.05).ConclusionPatients in the BP nonresponse group often have diabetes, a longer duration of hypertension, significantly reduced glomerular filtration rate, and heavier renal artery stenosis. CBP parameters are closely related to 24 h average SBP, and pre-operation IMAX and post-operation AUC2 are markers for a positive BP response.

BackgroundThe usefulness of lung ultrasound (LUS) in guiding heart failure (HF) treatment is still controversial.PurposeWe aimed to evaluate the usefulness of LUS-guided treatment vs. usual care in reducing the major adverse cardiac event (MACE) rate in patients with HF.Materials and methodsWe performed a systematic review and meta-analysis of randomized controlled trials (RCTs) identified through systematic searches of MEDLINE, EMBASE, the Cochrane Database, Google Scholar, and SinoMed. The primary outcome was MACEs (a composite of all-cause mortality, HF-related rehospitalization, and symptomatic HF). The required information size was calculated by trial sequential analysis (TSA).ResultsIn total, ten RCTs involving 1,203 patients were included. Overall, after a mean follow-up period of 4.7 months, LUS-guided treatment was associated with a significantly lower risk of MACEs than usual care [relative risk (RR), 0.59; 95% confidence interval (CI), 0.48–0.71]. Moreover, the rate of HF-related rehospitalization (RR, 0.63; 95% CI, 0.40–0.99) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentration (standardized mean difference, –2.28; 95% CI, –4.34 to –0.22) were markedly lower in the LUS-guided treatment group. The meta-regression analysis showed a significant correlation between MACEs and the change in B-line count (p < 0.05). The subgroup analysis revealed that the risk of MACEs was markedly lower in patients aged up to 70 years (RR, 0.54; 95% CI, 0.44–0.67), with a lower rate of atrial fibrillation (< 27.2%) (RR, 0.53; 95% CI, 0.43–0.67), and with a lower NT-proBNP concentration (< 3,433 pg/ml) (RR, 0.51; 95% CI, 0.40–0.64). TSA indicated a lower risk of MACEs with LUS-guided treatment than with usual care among patients with HF (p < 0.05).ConclusionLung ultrasound seems to be a safe and effective method to guide HF treatment.Systematic review registration[https://inplasy.com/], identifier [INPLASY202220124].

In recent decades, unmanned aerial vehicles (UAVs) have gained considerable popularity in the agricultural sector, in which UAV-based actuation is used to spray pesticides and release biological control agents. A key challenge in such UAV-based actuation is to account for wind speed and UAV flight parameters to maximize precision-delivery of pesticides and biological control agents. This paper describes a data-driven framework to predict density distribution patterns of vermiculite dispensed from a hovering UAV as a function of UAV’s movement state, wind condition, and dispenser setting. The model, derived by our proposed learning algorithm, is able to accurately predict the vermiculite distribution pattern evaluated in terms of both training and test data. Our framework and algorithm can be easily translated to other precision pest management problems with different UAVs and dispensers and for difference pesticides and crops. Moreover, our model, due to its simple analytical form, can be incorporated into the design of a controller that can optimize autonomous UAV delivery of desired amount of predatory mites to multiple target locations.

Background and ObjectiveRenal artery stenosis (RAS) is associated with an increased risk of renal function deterioration (RFD). Our previous study showed that renal cortical blood perfusion assessed by contrast-enhanced ultrasound (CEUS) was an important related factor for RFD in RAS patients. Based on several conventional related factors confirmed by previous studies, we aimed to establish and verify a CEUS+ scoring system to evaluate the risk of RFD at 1 year of follow-up in RAS patients.MethodsThis study was a single-center retrospective study. A total of 497 elderly RAS patients (247 in the training group and 250 in the verification group) admitted to the Beijing Hospital from January 2016 to December 2019 were included. The baseline characteristics of the patients on admission (including general conditions, previous medical history, blood pressure, blood creatinine, RAS, and cortical blood perfusion in the affected kidney) and renal function [glomerular filtration rate (GFR)] at 1-year of follow-up were collected. We used the univariate and multivariate logistic regressions to establish a CEUS+ scoring system model, the receiver operating characteristic (ROC) curve and area under the curve (AUC) to evaluate prediction accuracy, and the decision curve analysis and nomogram to evaluate the clinical application value of CEUS+ scoring system model.ResultsAmong the 497 patients enrolled, 266 (53.5%) were men, with an average age of (51.7 ± 19.3) years. The baseline clinical-radiomic data of the training group and the verification group were similar (all p > 0.05). Multivariate logistic regression analysis results showed that age [Odds ratio (OR) = 1.937, 95% confidence interval (CI): 1.104–3.397), diabetes (OR = 1.402, 95% CI: 1.015–1.938), blood pressure (OR = 1.575, 95% CI: 1.138–2.182), RAS (OR = 1.771, 95% CI: 1.114–2.816), and area under ascending curve (AUCi) (OR = 2.131, 95% CI: 1.263–3.596) were related factors for the renal function deterioration after 1 year of follow-up (all p < 0.05). The AUC of the ROC curve of the CEUS+ scoring system model of the training group was 0.801, and the Youden index was 0.725 (specificity 0.768, sensitivity 0.813); the AUC of the ROC curve of the validation group was 0.853, Youden index was 0.718 (specificity 0.693, sensitivity 0.835). There was no significant difference in ROC curves between the two groups (D = 1.338, p = 0.325). In addition, the calibration charts of the training and verification groups showed that the calibration curve of the CEUS+ scoring system was close to the standard curve (p = 0.701, p = 0.823, both p > 0.10).ConclusionThe CEUS+ scoring system model is helpful in predicting the risk of worsening renal function in elderly RAS patients.

ObjectivesTo explore the role of Contrast-enhanced ultrasound (CEUS) in the evaluation of patients with suspected renal artery stenosis and analyze the causes of the misdiagnosis and missed diagnosis.MethodsThe data of 40 patients (80 renal arteries) diagnosed with RAS by CEUS in Beijing Hospital from September 2018 to October 2020 were compared with their digital subtraction angiography (DSA) results to analyze the causes underlying missed diagnosis and misdiagnosis of RAS by CEUS.Results1. Compared with the gold standard DSA results, the AUC of the ROC curve of CEUS in detecting normal renal artery and renal artery stenosis was 0.961, the sensitivity was 96.4%, the specificity was 95.8%, and the Kappa value of the consistency analysis was 0.912 (P < 0.01); 2. Compared with the gold standard DSA results, the ROC curve of CEUS in distinguishing renal artery stenosis ≥70% from

BackgroundHepatocellular carcinoma (HCC) is the third cause of cancer-related deaths worldwide. L antigen family member 3 (LAGE3) is a prognostic biomarker and associated with progression in a variety of tumors. However, little has been reported about the role and potential mechanism of LAGE3 in HCC.MethodsThe clinical value and function of LAGE3 in HCC were obtained from multiple online databases. The potential functions and pathways of LAGE3 in HCC were analysed by R package of “clusterProfiler”. LAGE3 knockdown cells were constructed in HepG2, HuH7 and MHCC97H cell lines, respectively. The biological roles of LAGE3 were examined by in vitro and in vivo experiments.ResultsLAGE3 was upregulated in HCC tissues compared with normal tissues, and high expression of LAGE3 was significantly associated with several clinical characteristics and indicated a worse prognosis of HCC. The co-expressed genes of LAGE3 could be enriched in the mTOR signaling pathway in HCC. LAGE3 was upregulated in HCC cell lines. Functionally, knocking down LAGE3 expression not only increased apoptosis and inhibited growth rate, cell death mediated by T cells, colony formation, migration and invasion ability of HCC cell lines in vitro, but also reduced the progression of HCC in the subcutaneous xenotransplanted tumor model.ConclusionOur results suggested that LAGE3 served as an oncogenic factor of HCC and could be a potential biomarker and therapeutic target for HCC.

Background and PurposeAbout 70% of patients with radical surgery Cholangiocarcinoma (CCA) have recurrence and metastasis. There are few studies on the relationship between CCA adjuvant chemotherapy (mono or combined therapy), recurrence pattern (local, regional, distant recurrence) and prognosis [(Disease free survival, DFS), (Overall survival, OS)] after radical surgery. This study focuses on the correlation between CCA adjuvant chemotherapy, recurrence pattern and prognosis.MethodsThe study involved retrospective analysis of data: preoperative hematology, clinical pathology, adjuvant chemotherapy regimens, recurrence pattern, DFS and OS, of 207 patients with CCA. Chi-square test was used to analyze the correlation between related factors and postoperative recurrence. Survival curves were plotted by Kaplan-Meier method, P-values were calculated by Log-rank for univariate analysis, multivariate COX regression method for multivariate analysis.ResultsUsing chi-square test, there were correlations between high carbohydrate antigen 19-9 level(CA19-9≥35), vascular invasion, single-agent adjuvant chemotherapy and postoperative recurrences (p=0.04, p=0.04, p=0.02), COX multivariate regression analysis showed that adjuvant chemotherapy (single vs. doublet drug regimen) was an independent prognostic factor for DFS (11.0 vs. 24.6 months, HR=2.88, P=0.01), whereas recurrence pattern (local vs. distant; regional vs. distant) was an independent prognostic factor for OS (31.2 months vs. 20.4 months, HR=0.58, p=0.01; 32.0 months vs. 20.4 months, HR=0.51, p=0.01).ConclusionAdjuvant chemotherapy regimen was an independent prognostic factor of DFS, whereas recurrence patterns were independent prognostic factors for OS. adjuvant chemotherapy with doublet drug regimen was correlated with longer DFS, and different recurrence modes affect OS.

Chiral quantum optics and Topological photonics are both emerging field of research, which have attracted great attention in recent years. Chiral quantum optics provides a new approach to achieve full quantum control of light-matter interaction in a novel manner, which has potential possibility for the implementation of complex quantum information networks. Meanwhile, topological photonics provides a novel route for designing and realizing optical device with unprecedented functionality, such as robust light propagation, the immunity to various structural imperfection, back-scattering suppression as well as unidirectional transmission. The application of topological photonics in chiral quantum optics will promote the whole performance of integrated quantum device with topological protection. In this review, we summarize the progress of chiral quantum optics and topological photonics firstly. Then, we mainly focus on the research of topological chiral edge states based on photonic quantum spin-Hall effect and photonic quantum valley-Hall effect. Furthermore, we introduce the recent work of chiral topological quantum interface formed by embedding quantum dot into the interface between two topologically distinct photonic crystal structures. At last, we give short outlook on the future development direction and prospect for application of topological chiral quantum interface.

Transparent cellulose nanowhisker (CNW)/graphene nanoplatelet (GN) composite films were produced via sonication mixing and solution casting methods. Such composite films exhibited improved thermal, electrical and mechanical properties. The material morphologies and microstructures were examined using scanning electronic microscopy (SEM), X-ray diffraction (XRD) analysis and Raman spectroscopy. Strong interaction was detected when CNWs were randomly attached onto graphene sheets, as evidenced by SEM images obtained in this study. In particular, the addition of GNs into CNWs had significant effect on the thermal behavior of composite films. The melting temperature (Tm) and initial thermal decomposition temperature (Tid) of CNW films were both increased by 23.2, 29.3, 26.3°C, and 70.2, 88.4, 87.8°C with the inclusions of 0.1, 0.25, and 0.5 wt% GNs, respectively. The electrical conductivity of composite films was enhanced in a monotonically increasing manner with the maximum level of 4.0 × 10−5 S/m detected at the GN content of 0.5 wt%. Their tensile strength was also improved by maximum 33.7% when increasing the GN content up to 0.25 wt% as opposed to that of CNW films. Such CNW/GN composite films can be potentially used in green anti-static and electronic packaging applications.

RNA silencing is a conserved mechanism in plants that targets viruses. Viral small RNAs (vsiRNAs) can be generated from viral double-stranded RNA replicative intermediates within the infected host, or from host RNA-dependent RNA polymerases activity on viral templates. The abundance and profile of vsiRNAs in viral infections have been reported previously. However, the involvement of vsiRNAs during infection of the Geminiviridae family member cotton leaf curl virus (CLCuD), which causes significant economic losses in cotton growing regions, remains largely uncharacterized. Cotton leaf curl Multan virus (CLCuMuV) associated with a betasatellite called Cotton leaf curl Multan betasatellite (CLCuMuB) is a major constraint to cotton production in South Asia and is now established in Southern China. In this study, we obtained the profiles of vsiRNAs from CLCuMV and CLCuMB in infected upland cotton (Gossypium hirsutum) plants by deep sequencing. Our data showed that vsiRNA that were derived almost equally from sense and antisense CLCuD DNA strands accumulated preferentially as 21- and 22-nucleotide (nt) small RNA population and had a cytosine bias at the 5’-terminus. Polarity distribution revealed that vsiRNAs were almost continuously present along the CLCuD genome and hotspots of sense and antisense strands were mainly distributed in the Rep proteins region of CLCuMuV and in the C1 protein of CLCuMuB. In addition, hundreds of host transcripts targeted by vsiRNAs were predicted, many of which encode transcription factors associated with biotic and abiotic stresses. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis of selected potential vsiRNA targets showed that some targets were significantly down-regulated in CLCuD-infected cotton plants. We also verified the potential function of vsiRNA targets that may be involved in CLCuD infection by virus-induced gene silencing (VIGS) and 5’-rapid amplification of cDNA end (5’-RACE). Here, we provide the first report on vsiRNAs responses to CLCuD infection in cotton.

Background: The prognostic value and immune significance of T-cell proliferation regulators (TCRs) in hepatocellular carcinoma (HCC) have not been previously reported. This study aimed to develop a new prognostic model based on TCRs in patients with HCC. Method: This study used The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and International Cancer Genome Consortium-Liver Cancer-Riken, Japan (ICGC-LIRI-JP) datasets along with TCRs. Differentially expressed TCRs (DE-TCRs) were identified by intersecting TCRs and differentially expressed genes between HCC and non-cancerous samples. Prognostic genes were determined using Cox regression analysis and were used to construct a risk model for HCC. Kaplan-Meier survival analysis was performed to assess the difference in survival between high-risk and low-risk groups. Receiver operating characteristic curve was used to assess the validity of risk model, as well as for testing in the ICGC-LIRI-JP dataset. Additionally, independent prognostic factors were identified using multivariate Cox regression analysis and proportional hazards assumption, and they were used to construct a nomogram model. TCGA-LIHC dataset was subjected to tumor microenvironment analysis, drug sensitivity analysis, gene set variation analysis, and immune correlation analysis. The prognostic genes were analyzed using consensus clustering analysis, mutation analysis, copy number variation analysis, gene set enrichment analysis, and molecular prediction analysis. Results: Among the 18 DE-TCRs, six genes (DCLRE1B, RAN, HOMER1, ADA, CDK1, and IL1RN) could predict the prognosis of HCC. A risk model that can accurately predict HCC prognosis was established based on these genes. An efficient nomogram model was also developed using clinical traits and risk scores. Immune-related analyses revealed that 39 immune checkpoints exhibited differential expression between the high-risk and low-risk groups. The rate of immunotherapy response was low in patients belonging to the high-risk group. Patients with HCC were further divided into cluster 1 and cluster 2 based on prognostic genes. Mutation analysis revealed that HOMER1 and CDK1 harbored missense mutations. DCLRE1B exhibited an increased copy number, whereas RAN exhibited a decreased copy number. The prognostic genes were significantly enriched in tryptophan metabolism pathways. Conclusions: This bioinformatics analysis identified six TCR genes associated with HCC prognosis that can serve as diagnostic markers and therapeutic targets for HCC. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA). Methods: Data of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality. Results: A total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076-1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760-1.303]) and all-cause mortality (HR, 1.402 [0.887-2.215]). Conclusion: Tofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality. [ABSTRACT FROM AUTHOR]

Introduction: Monoecy is usually interpreted as an important evolutionary route of the plant sexual system from hermaphroditism to dioecy. This floral mechanism can effectively reduce self-interference during the reproductive process, and the services provided by pollinators may play an essential role in monoecious species; however, relevant research is still lacking. Thus, we aimed to determine whether monoecious plants could effectively avoid selfinterference and promote the evolution of monoecy under the service of pollinators. Methods: Here, we successfully performed manipulation experiments to test self-compatibility, pollinator behavior, and self-interference between male and female functions in Akebia trifoliata, a typical monoecious species. Results: We demonstrated that experimental self-pollination did not yield any fruit, and supplemental pollination significantly increased fruit set and fruit weight compared to natural pollination, suggesting that this species is completely selfincompatible and experiences strong pollen limitation. Simultaneous self- and cross-pollination and self-pollination prior to cross-pollination significantly reduced reproductive fitness, but self-pollination after cross-pollination did not, indicating self-interference in this plant. Moreover, both male flower probing preference and switching modes within inflorescences by pollinators successfully reinforced self-interference and were also responsible for decreasing reproductive fitness in A. trifoliata. Discussion: In summary, pollinator-mediated self-interference significantly reduced selfing, providing potential dynamics for the maintenance and evolution of monoecy. [ABSTRACT FROM AUTHOR]

Objective: Bipolar disorder (BD) and major depressive disorder (MDD) are two common psychiatric disorders. Due to the overlapping clinical symptoms and the lack of objective diagnostic biomarkers, bipolar disorder (BD) is easily misdiagnosed as major depressive disorder (MDD), which in turn affects treatment decisions and prognosis. This study aimed to investigate biomarkers that could be used to differentiate BD from MDD. Methods: Nuclear magnetic resonance (NMR) spectroscopy was performed to assess serum metabolic profiles in depressed patients with BD (n = 59), patients with MDD (n = 14), and healthy controls (n = 10). Data was analyzed using partial least squares discriminant analysis, orthogonal partial least squares discriminant analysis and t-tests. Different metabolites (VIP > 1 and p < 0.05) were identified and further analyzed using Metabo Analyst 5.0 to identify relevant metabolic pathways. Results: The metabolic phenotypes of the BD and MDD groups were significantly different from those of the healthy controls, and there were different metabolite differences between them. In the BD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, β-glucose, pantothenic acid, mannose, glycerol, and lipids were significantly higher than those in the healthy control group, and the levels of lactate and acetoacetate were significantly lower than those in the healthy control group. In the MDD group, the levels of 3-hydroxybutyric acid, n-acetyl glycoprotein, pyruvate, choline, acetoacetic acid, and lipids were significantly higher than those of healthy controls, and the levels of acetic acid and glycerol were significantly lower than those of healthy controls. Conclusion: Glycerolipid metabolism is significantly involved in BD and MDD. Pyruvate metabolism is significantly involved in MDD. Pyruvate, choline, and acetate may be potential biomarkers for MDD to distinguish from BD, and pantothenic acid may be a potential biomarker for BD to distinguish from MDD. [ABSTRACT FROM AUTHOR]

Objectives: This study compared different extraction methods of Yizhiqingxin formula (YQF) and its neuroprotective effects based on pharmacodynamic indices such as learning and memory ability, brain tissue histopathology and morphology, and inflammatory factor expression in a mouse model of Alzheimer's disease (AD). Methods: The pharmaceutical components of YQF were extracted using three extraction processes, and the components were analyzed by high performance liquid chromatography. Donepezil hydrochloride was used as a positive control drug. Fifty 7-8-month-old 3 x Tg AD mice were randomly divided into three YQF groups (YQF-1, YQF-2, and YQF-3), a donepezil group, and a model group. Ten age-matched C57/BL6 mice were used as normal controls. YQF and Donepezil were administered by gavage at a clinically equivalent dose of 2.6 and 1.3 mg·kg-1·d-1, respectively, with a gavage volume of 0.1 ml/10 g. Control and model groups received equal volumes of distilled water by gavage. After 2 months, the efficacy was evaluated using behavioral experiments, histopathology, immunohistochemistry, and serum assays. Results: The main components in YQF are ginsenoside Re, ginsenoside Rg1, ginsenoside Rb1, epiberberine, coptisine chloride, palmatine, berberine, and ferulic acid. YQF-3 (alcohol extraction) has the highest content of active compounds, followed by YQF-2 (water extraction and alcohol precipitation method). Compared to the model group, the three YQF groups showed alleviated histopathological changes and improved spatial learning and memory, with the effect in YQF-2 being the most significant. YQF showed protection of hippocampal neurons, most significantly in the YQF-1 group. YQF significantly reduced Ab pathology and tau hyperphosphorylation, decreased expressions of serum pro-inflammatory factors interleukin-2 and interleukin-6 as well as serum chemokines MCP-1 and MIG. Conclusion: YQF prepared by three different processes showed differences in pharmacodynamics in an AD mouse model. YQF-2 was significantly better than the other extraction processes in improving memory. [ABSTRACT FROM AUTHOR]

BackgroundEndoscopic thoracoscopic sympathectomy (ETS) is the preferred method for treating primary palmar hyperhidrosis (PPH) that bears the risk of compensatory hyperhidrosis (CH) following surgery. The current study aims to evaluate the effectiveness and safety of an innovative surgical procedure of ETS.MethodsA survey of the clinical data of 109 patients with PPH who underwent ETS in our department from May 2018 to August 2021 was retrospectively conducted. The patients were organized into two groups. Group A underwent R4 sympathicotomy combined with R3 ramicotomy. Group B underwent R3 sympathicotomy. Patients were followed up to evaluate the safety, effectiveness and the incidence of postoperative CH of the modified surgical approach.ResultsA total of 102 patients completed follow-up, and seven of the total enrolled patients were lost to follow-up, with a loss rate of 6% (7/109). Among these, Group A constitutes 54 cases, group B constitutes 48 cases, and the mean follow-up was 14 months (interquartile range 12–23 months). There was no statistically difference in surgical safety, postoperative efficacy, and postoperative quality of life (QoL) score between group A and group B (p > 0.05). The score of the psychological assessment was higher (p = 0.004) in group A (14.15 ± 2.06) compared to group B (13.30 ± 1.86). The incidence of CH in group A was lower than in group B (p = 0.019).ConclusionR4 sympathicotomy combined with R3 ramicotomy is safe and effective for PPH treatment, along with a reduced incidence of postoperative CH rate and improved postoperative psychological satisfaction.

Viral infections trigger the innate immune system, serving as the first line of defense, and are characterized by the production of type I interferon (IFN). Type I IFN is expressed in a broad spectrum of cells and tissues in the host and includes various subtypes (IFN-α, IFN-β, IFN-δ, IFN-E, IFN-κ, IFN-τ, IFN-ω, IFN-ν, and IFN-ζ). Since the discovery of type I IFN, our knowledge of the biology of type I IFN has accumulated immensely, and we now have a substantial amount of information on the molecular mechanisms of the response and induction of type I IFN, as well as the strategies utilized by viruses to evade the type I IFN response. Foot-and-mouth disease virus (FMDV) can selectively alter cellular pathways to promote viral replication and evade antiviral immune activation of type I IFN. RNA molecules generated by FMDV are sensed by the cellular receptor for pathogenassociated molecular patterns (PAMPs). FMDV preferentially activates different sensor molecules and various signal transduction pathways. Based on knowledge of the virus or RNA pathogen specificity as well as the function-structure relationship of RNA sensing, it is necessary to summarize numerous signaling adaptors that are reported to participate in the regulation of IFN gene activation. [ABSTRACT FROM AUTHOR]

Quercetin exerts anti-inflammatory, anti-oxidant and other protective effects. Previous studies have shown that senescent cells, such as fibroblasts and type II airway epithelial cells, are strongly implicated in the development of pulmonary fibrosis pathology. However, the role of senescent macrophages during silicosis remains unclear. We investigated the effects of quercetin on macrophage senescence and pulmonary fibrosis, and explored underlying mechanisms. Mice were randomized to six model groups. Vitro model was also established by culturing RAW264.7 macrophages with silica (SiO2). We examined the effects of quercetin on fibrosis, senescence-associated β-galactosidase (SA-β-Gal) activity, and senescence-specific genes (p16, p21, and p53). We showed that quercetin reduced pulmonary fibrosis and inhibited extracellular matrix (ECM) formation. Quercetin also attenuated macrophage senescence induced by SiO2 both in vitro and in vivo. In addition, quercetin significantly decreased the expressions of the senescence-associated secretory phenotype (SASP), including proinflammatory factors (interleukin-1α (Il-1α), Il-6, tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1)) and matrix metalloproteinases (MMP2, MMP9, and MMP12). In conclusion, quercetin mediated its anti-fibrotic effects by inhibiting macrophage senescence, possibly via SASP.

The pathological manifestations of fatal cases of human hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) are characterized by inflammatory damage to the central nervous system (CNS). Here, the dynamic distribution of EV71 in the CNS and the subsequent pathological characteristics within different regions of neonatal rhesus macaque brain tissue were studied using a chimeric EV71 expressing green fluorescence protein. The results were compared with brain tissue obtained from the autopsies of deceased EV71-infected HFMD patients. These observations suggested that the virus was prevalent in areas around the blood vessels and nerve nuclei in the brain stem and showed a preference for astrocytes in the CNS. Interestingly, infected astrocytes within the in vivo and in vitro human and macaque systems exhibited increased expression of excitatory neurotransmitters and cytokines that also stimulated the neuronal secretion of the excitatory neurotransmitters noradrenalin and adrenalin, and this process most likely plays a role in the pathophysiological events that occur during EV71 infection. [ABSTRACT FROM AUTHOR]

Hysteroscopic procedures complicated by air embolism (AE) are exceptionally rare occurrences in clinical practice, and there have been no previously reported cases of AE associated with hysteroscopic dilation and curettage. While the overall incidence of this complication is low, the consequences can be devastating. During early pregnancy, the unique physiological changes, such as elevated hormonal levels and increased uterine blood supply, significantly heighten the risk of AE development. Therefore, the prompt recognition of early signs and symptoms, coupled with the implementation of timely and effective interventions, are crucial to improve patient survival rates and minimize the risk of long-term sequelae. This case report presents the characteristic clinical manifestations and imaging findings associated with AE, providing a valuable clinical reference for obstetricians and gynecologists to recognize this rare yet potentially life-threatening complication of hysteroscopic procedures. Early detection and appropriate management are essential to optimize patient outcomes and prevent catastrophic consequences.

ObjectiveMaternal syphilis could cause serious consequences. The aim of this study was to identify risk factors for maternal syphilis in order to predict an individual's risk of developing adverse pregnancy outcomes (APOs).MethodsA retrospective study was conducted on 768 pregnant women with syphilis. A questionnaire was completed and data analyzed. The data was divided into a training set and a testing set. Using logistic regression to establish predictive models in the training set, and its predictive performance was evaluated in the testing set. The probability of APOs occurrence is presented through a nomogram.ResultsCompared with the APOs group, pregnant women in the non-APOs group participated in a longer treatment course. Course, time of the first antenatal care, gestation week at syphilis diagnosis, and gestation age at delivery in weeks were independent predictors of APOs, and they were used to establish the nomogram.ConclusionsOur study investigated the impact of various characteristics of syphilis pregnant women on pregnancy outcomes and established a prediction model of APOs in Suzhou. The incidence of APOs can be reduced by controlling for these risk factors.

Alzheimer’s disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the beta-amyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

Aerobic glycolysis is a recognized feature shared by tumors, leading to the accumulation of lactic acid in their local microenvironments. Like the tumors, the blastocysts, placenta, trophoblasts and decidual immune cells can also produce a large amount of lactic acid through aerobic glycolysis during the early pregnancy. Moreover, the placenta expresses the transporters of the lactic acid. While several studies have described the role of lactic acid in the tumor microenvironment, especially lactic acid's modulation of immune cells, the role of lactic acid produced during pregnancy is still unclear. In this paper, we reviewed the scientific evidence detailing the effects of lactic acid in the tumor microenvironment. Based on the influence of the lactic acid on immune cells and tumors, we proposed that lactic acid released in the unique uterine environment could have similar effects on the trophoblast cells and immune cells during the early pregnancy.