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4′,5,7-Trihydroxy-8-methoxyflavone is an anticancer monomer component isolated from the traditional Chinese medicine Sorbaria sorbifolia. 4′,5-Dihydroxy-7-piperazinemethoxy-8-methoxy flavonoids (DMF) with good solubility and anti-tumor effects was obtained by chemical modification in the early stage. This study explored the mechanism by which DMF regulates the mitochondrial apoptosis of human hepatoma cells through Bcl-2-associated transcription factor 1 (Bclaf1). DMF inhibited the proliferation of human hepatoma cells in a concentration- and time-dependent manner and induced cell mitochondrial apoptosis. The molecular docking and cell assay results demonstrated that DMF inhibits Bclaf1 expression by binding to its active site. Lentivirus transfection was used to construct cells with stable knockout and overexpression of Bclaf1, and a Hep3B xenograft model was constructed in nude mice. The mechanism by which DMF induced the mitochondrial apoptosis of human hepatoma cells through Bclaf1 was further verified in vitro and in vivo. These findings indicated that DMF induced human hepatoma cell mitochondrial apoptosis through Bclaf1.

BackgroundA substantial amount of research has explored the intricate relationship between exercise and sleep quality, consistently confirming that exercise can effectively enhance sleep quality. Nevertheless, previous studies have yet to conclusively determine which specific exercise program is most efficacious in improving sleep quality. To address this gap, the present study systematically evaluated the differential effects of various types of exercise, as well as exercise dosages (including duration, intervention period, frequency, and intensity), on sleep outcomes using a network meta-analysis approach. This endeavor aims to provide evidence-based support for the development of scientifically effective exercise programs tailored to improve sleep quality.MethodsThrough the Web of Science, PubMed, Cochrane Library, Embase, and Scopus databases, we conducted a search for randomized controlled trials investigating the effects of exercise interventions on sleep, with a search cutoff date of April 30, 2024. We rigorously selected the literature according to the PICOS principle, and two independent researchers extracted the data. We would like to change this passage to: Bias risk assessment was conducted using the RevMan 5.4 software, and traditional meta-analysis and network meta-analysis were performed using Stata 17.0 software to generate forest plots, network evidence plots, and funnel plots. Furthermore, we adopted the surface under the cumulative ranking curve (SUCRA) to evaluate and rank the intervention effects of different exercise types and dosages on sleep quality. To verify the robustness of our study results, we performed a sensitivity analysis using the leave-one-out method.ResultsThe study strictly adhered to the PRISMA guidelines and included 58 RCT papers with a total of 5,008 participants. The network meta-analysis revealed significant variations in the impact of exercise frequency on sleep outcomes when compared to the control group. Interventions of 1–2 times per week [SMD = −0.85, 95% CI (−1.43, −0.26)], 3 times per week [SMD = −0.45, 95% CI (−0.80, −0.11)], and 4 times per week [SMD = −1.09, 95% CI (−1.92, −0.26)] demonstrated the most notable effects. Interventions lasting ≤30 min and 60–65 min were significantly more effective than the control group, with ≤30 min proving significantly more effective than 40–55 min [SMD = 0.75, 95% CI (0.01, 1.49)]. Interventions lasting 9–10 weeks [SMD = −1.40, 95% CI (−2.37, −0.44)], 12–16 weeks [SMD = −0.55, 95% CI (−0.90, −0.20)], and ≥ 24 weeks [SMD = −0.71, 95% CI (−1.31, −0.10)] were all significantly more effective than the control group. Additionally, the 9–10 weeks intervention period was found to be significantly more effective than the 6–8 weeks period [SMD = −1.21, 95% CI (−2.37, −0.04)]. Furthermore, interventions of moderate intensity [SMD = −1.06, 95% CI (−1.52, −0.61)] and high intensity [SMD = −1.48, 95% CI (−2.55, −0.40)] exercise interventions yielded significantly greater benefits compared to the control group. Specifically, high intensity interventions [SMD = −1.97, 95% CI (−3.37, −0.56)] and moderate intensity [SMD = −1.55, 95% CI (−2.57, −0.54)] exercise interventions were found to be significantly more effective than moderate-high intensity interventions. In terms of exercise types, aerobic exercise [SMD = −0.56, 95% CI (−0.86, −0.27)], traditional Chinese exercises [SMD = −0.57, 95% CI (−0.97, −0.18)], and combined exercise [SMD = −0.99, 95% CI (−1.66, −0.32)] interventions all produced significant improvements compared to the control group. The study determined that the most effective combination of exercise prescription elements for enhancing sleep quality includes a frequency of 4 times per week (SUCRA = 84.7), a duration of ≤30 min (SUCRA = 92.2), a period of 9–10 weeks (SUCRA = 89.9), and high-intensity (SUCRA = 92.9) combined exercise (SUCRA = 82.7).ConclusionThe current evidence indicates that combined exercise with a frequency of 4 times per week, a duration of ≤30 min, a period of 9–10 weeks, and high intensity is most effective for improving sleep quality. Nevertheless, due to the limited number of studies included, further research is needed to enhance the reliability of the findings.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier: CRD42024555428.

PurposeThis study aimed to evaluate the optical coherence tomography angiography (OCTA) changes in subzones of peripapillary atrophy (PPA) among type 2 diabetic patients (T2DM) with or without diabetic retinopathy (DR) using well-designed deep learning models.MethodsA multi-task joint deep-learning model was trained and validated on 2,820 images to automate the determination and quantification of the microstructure and corresponding microcirculation of beta zone and gamma zone PPA. This model was then applied in the cross-sectional study encompassing 44 eyes affected by non-proliferative diabetic retinopathy (NPDR) and 46 eyes without DR (NDR). OCTA was utilized to image the peripapillary area in four layers: superficial capillary plexus (SCP), deep capillary plexus (DCP), choroidal capillary (CC) and middle-to-large choroidal vessel (MLCV).ResultsThe patients in both groups were matched for age, sex, BMI, and axial length. The width and area of the gamma zone were significantly smaller in NPDR group compared to the NDR group. Multiple linear regression analysis revealed a negative association between the diagnosis of DR and the width and area of the gamma zone. The gamma zone exhibited higher SCP, DCP and MLCV density than the beta zone, while the beta zone showed higher CC density than the gamma zone. In comparison to the NDR group, the MLCV density of gamma zone was significantly lower in NPDR group, and this density was positively correlated with the width and area of the gamma zone.DiscussionDR-induced peripapillary vascular changes primarily occur in gamma zone PPA. After eliminating the influence of axial length, our study demonstrated a negative correlation between DR and the gamma zone PPA. Longitudinal studies are required to further elucidate the role of the gamma zone in the development and progression of DR.

Visceral white adipose tissues (WAT) regulate systemic lipid metabolism and inflammation. Dysfunctional WAT drive chronic inflammation and facilitate atherosclerosis. Adipose tissue-associated macrophages (ATM) are the predominant immune cells in WAT, but their heterogeneity and phenotypes are poorly defined during atherogenesis. The scavenger receptor CD36 mediates ATM crosstalk with other adipose tissue cells, driving chronic inflammation. Here, we combined the single-cell RNA sequencing technique with cell metabolic and functional assays on major WAT ATM subpopulations using a diet-induced atherosclerosis mouse model (Apoe-null). We also examined the role of CD36 using Apoe/Cd36 double-null mice. Based on transcriptomics data and differential gene expression analysis, we identified a previously undefined group of ATM displaying low viability and high lipid metabolism and labeled them as “unhealthy macrophages”. Their phenotypes suggest a subpopulation of ATM under lipid stress. We also identified lipid-associated macrophages (LAM), which were previously described in obesity. Interestingly, LAM increased 8.4-fold in Apoe/Cd36 double-null mice on an atherogenic diet, but not in Apoe-null mice. The increase in LAM was accompanied by more ATM lipid uptake, reduced adipocyte hypertrophy, and less inflammation. In conclusion, CD36 mediates a delicate balance between lipid metabolism and inflammation in visceral adipose tissues. Under atherogenic conditions, CD36 deficiency reduces inflammation and increases lipid metabolism in WAT by promoting LAM accumulation.

BackgroundThe objective of this study was to conduct a systematic review and meta-analysis of the clinical application effects of transnasal high flow nasal cannula compared to other conventional modalities for oxygen therapy devices in patients undergoing bronchoscopy.MethodsA comprehensive literature search was conducted in multiple English databases, including PubMed, Web of Science, and Cochrane Library, to collect relevant studies on the application of high flow nasal cannula in patients undergoing bronchoscopy, and conducted a meta-analysis utilizing RevMan 5.4 software, following the predetermined inclusion and exclusion criteria.ResultsA total of 12 studies meeting the inclusion criteria were included, involving 1,631 patients (HFNC group: n = 811, other oxygen therapy group: n = 820). The meta-analysis results demonstrated that HFNC significantly reduced the incidence of hypoxemia and improved the minimum oxygen saturation compared to conventional oxygen therapy (RR = 0.27, 95% CI: 0.18–0.41, p

In recent years, porcine diarrhea-associated viruses have caused significant economic losses globally. These viruses present similar clinical symptoms, such as watery diarrhea, dehydration, and vomiting. Co-infections with porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV) are common. For the rapid and on-site preliminary diagnosis on the pig farms, this study aimed to develop a colloidal gold immunochromatography assay (GICA) strip for the detection of PEDV and TGEV simultaneously. The GICA kit showed that there was no cross-reactivity with the other five common porcine viruses. With visual observation, the lower limits were approximately 104 TCID50/mL and 104 TCID50/mL for PEDV and TGEV, respectively. The GICA strip could be stored at 4°C or 25°C for 12 months without affecting its efficacy. To validate the GICA strip, 121 clinical samples were tested. The positive rates of PEDV and TGEV were 42.9 and 9.9%, respectively, and the co-infection rate of the two viruses was 5.8% based on the duplex GICA strip. Thus, the established GICA strip is a rapid, specific, and stable tool for on-site preliminary diagnosis of PEDV- and TGEV-associated diarrhea.

BackgroundFood waste remains a major problem for the world and food security. Despite the fact that consumers are significant producers of food waste, little research attention has been paid to college students. The present study aimed to assess food waste and the influence factors among college students. Additionally, the goal was to improve college students’ food waste attitudes and behaviors through labor education.MethodsThrough an online questionnaire survey, 407 college students from three universities were asked about food waste; 27 students of them were randomly selected as the research object, and labor practice was carried out in groups in the student cafeteria. Mann–Whitney U test was performed to show food waste behavior of college students and logistical regression analysis was used to analyze the factors affecting food waste behavior.ResultsThe results indicated that the food waste is more serious among college students in East China, senior or female students, BMI plays a positive role in food waste among college students, while monthly consumption and peers waste play a negative role in food waste. After participating in the labor education, the students’ views and practices toward their peer’s food waste have improved.ConclusionThe implementation of labor education in college canteens is conducive to the establishment of a correct outlook on labor as well as saving consciousness among college students, and to the formation of a social consciousness of saving.

Background: The impact of female reproductive factors, including age at menarche (AAM), age at first birth (AFB), age at first sexual intercourse (AFS), age at natural menopause (ANM), and pregnancy abortion (PA), on the risk of developing frailty remains uncertain. Our objective is to examine the potential causal relationship between female reproductive traits and frailty through the utilization of two-sample univariable Mendelian Randomization (UVMR) and multivariable Mendelian Randomization (MVMR) analyses.Methods: Leveraging large-scale Genome-Wide Association Study (GWAS) data from individuals of European ancestry, we performed two-sample UVMR and MVMR analyses to examine the causal relationship between female reproductive traits and frailty. The primary analysis employed inverse-variance-weighted (IVW) estimation, and sensitivity analyses were conducted to assess the robustness of the findings.Results: The UVMR analysis revealed a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty [IVW: OR = 0.74, 95%CI(0.70–0.79), p = 0.000; OR = 0.93, 95%CI(0.92–0.95), p = 0.000; OR = 0.96, 95%CI(0.95–0.98), p = 0.000]. However, there was no significant effect of ANM and PA on frailty (p > 0.05). The sensitivity analysis results were robust, supporting the findings. Furthermore, this association remained significant even after adjusting for body mass index (BMI) and educational attainment (EA) in the MVMR analysis [IVW: OR = 0.94, 95%Cl (0.91–0.97), p = 0.000; OR = 0.77, 95%Cl (0.70–0.86), p = 0.000; OR = 0.95, 95%Cl (0.94–0.97), p = 0.000]. BMI and EA serve as mediators in this process.Conclusion: Our research has established a significant causal relationship between female reproductive traits (AFS, AFB, AAM) and frailty, with BMI and EA acting as mediating factors in this process. However, further research is warranted to validate our findings and elucidate the underlying biological mechanisms.

ObjectiveTo explore the effectiveness of machine learning classifiers based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the expression levels of CD3+, CD4+, and CD8+ tumor-infiltrating lymphocytes (TILs) in patients with advanced gastric cancer (AGC).MethodsThis study investigated 103 patients with confirmed AGC through DCE-MRI and immunohistochemical staining. Immunohistochemical staining was used to evaluate CD3+, CD4+, and CD8+ T-cell expression. Utilizing Omni Kinetics software, radiomics features (Ktrans, Kep, and Ve) were extracted and underwent selection via variance threshold, SelectKBest, and LASSO methods. Logistic regression (LR), support vector machine (SVM), random forest (RF), and eXtreme Gradient Boosting (XGBoost) are the four classifiers used to build four machine learning (ML) models, and their performance was evaluated using 10-fold cross-validation. The model’s performance was evaluated and compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value, and negative predictive value.ResultsIn terms of CD3+, CD4+, and CD8+ T lymphocyte prediction models, the random forest model outperformed the other classifier models in terms of CD4+ and CD8+ T cell prediction, with AUCs of 0.913 and 0.970 on the training set and 0.904 and 0.908 on the validation set, respectively. In terms of CD3+ T cell prediction, the logistic regression model fared the best, with AUCs on the training and validation sets of 0.872 and 0.817, respectively.ConclusionMachine learning classifiers based on DCE-MRI have the potential to accurately predict CD3+, CD4+, and CD8+ tumor-infiltrating lymphocyte expression levels in patients with AGC.

BackgroundCerebral small vessel disease (CSVD) attaches people’s attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients.MethodsWe collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD.ResultsVessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (β: −0.087, 95%CI: −0.166, −0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately].ConclusionSRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

ObjectivesTo investigate the characteristic cytokine profile of the aqueous humor in eyes with congenital cataract and pre-existing posterior capsule dysfunction (PCD).MethodsIn this cross-sectional study, the enrolled eyes with congenital cataract and PCD were included in the PCD group, while those with an intact posterior capsule were included in the control group. Demographic data and biometric parameters were recorded. The levels of 17 inflammatory factors in the aqueous humor collected from the enrolled eyes were detected using Luminex xMAP technology, and intergroup differences in the collected data were analyzed.ResultsThe PCD group comprised 41 eyes from 31 patients with congenital cataract and PCD, whereas the control group comprised 42 eyes from 27 patients with congenital cataract and an intact posterior capsule. Lens thickness was significantly thinner in the PCD group than in the control group. However, the levels of monocyte chemoattractant protein-1 (MCP-1), transforming growth factor-β2 (TGF-β2), and vascular endothelial growth factor (VEGF) were significantly higher in the PCD group than in the control group. Multivariate logistic regression confirmed that lens thickness and TGF-β2 level were independent risk factors for PCD.ConclusionA thinner lens thickness in eyes with congenital cataract and PCD could serve as a biometric feature of these eyes. The higher levels of MCP-1, TGF-β2, and VEGF in eyes with PCD indicated a change in their intraocular inflammatory microenvironment, which possibly led to cataract progression. Lens thickness and TGF-β2 level are independent risk factors for PCD.

Background and aimChinese herbal injection (CHI) is a widely used preparation for advanced non-small cell lung cancer (NSCLC) treatment to alleviate the adverse drug reactions and enhance the clinical efficacy of chemotherapy. However, its efficacy and safety in combination with platinum-based chemotherapy (PBC) remain poorly understood owing to the lack of high-level evidence in the face of a wide variety of CHIs. Therefore, in this study, we aimed to explore the efficacy and safety of CHIs in combination with PBC regimens in the treatment of mid- and advanced NSCLC.MethodsSystematic evaluation and meta-analysis were conducted as per the Preferred Reporting Project for Systematic Evaluation and Meta-Analysis Protocols (PRISMA-P). Seven databases were comprehensively searched for relevant randomized controlled trials (RCTs) through August 1, 2022. The quality of each study was evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. Statistical analysis was performed using Revman 5.3, with dichotomies expressed as risk ratio (RR) and 95% confidence interval (CI). Objective response rate (ORR) and disease control rate (DCR) were selected as the primary outcomes, with quality of life (QoL) and toxic side effects as secondary outcomes.ResultsA total of 140 RCTs were included in this study. The results of the meta-analysis suggested that, compared with PBC alone, PBC combined with CHIs significantly improved the ORR (RR=1.35, 95% CI: 1.30–1.41, P

DEK protein is highly expressed in asthma. However, the mechanism of DEK on mitophagy in asthma has not been fully understood. This study aims to investigate the role and mechanism of DEK in asthmatic airway inflammation and in regulating PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. PINK1-Parkin mitophagy, NLRP3 inflammasome, and apoptosis were examined after gene silencing or treatment with specific inhibitors (MitoTEMPO, MCC950, and Ac-DEVD-CHO) in house dust mite (HDM) or recombinant DEK (rmDEK)-induced WT and DEK-/- asthmatic mice and BEAS-2B cells. The regulatory role of DEK on ATAD3A was detected using ChIP-sequence and co-immunoprecipitation. rmDEK promoted eosinophil recruitment, and co-localization of TOM20 and LC3B, MFN1 and mitochondria, LC3B and VDAC, and ROS generation, reduced protein level of MnSOD in HDM induced-asthmatic mice. Moreover, rmDEK also increased DRP1 expression, PINK1-Parkin-mediated mitophagy, NLRP3 inflammasome activation, and apoptosis. These effects were partially reversed in DEK-/- mice. In BEAS-2B cells, siDEK diminished the Parkin, LC3B, and DRP1 translocation to mitochondria, mtROS, TOM20, and mtDNA. ChIP-sequence analysis showed that DEK was enriched on the ATAD3A promoter and could positively regulate ATAD3A expression. Additionally, ATAD3A was highly expressed in HDM-induced asthma models and interacted with DRP1, and siATAD3A could down-regulate DRP1 and mtDNA-mediated mitochondrial oxidative damage. Conclusively, DEK deficiency alleviates airway inflammation in asthma by down-regulating PINK1-Parkin mitophagy, NLRP3 inflammasome activation, and apoptosis. The mechanism may be through the DEK/ATAD3A/DRP1 signaling axis. Our findings may provide new potential therapeutic targets for asthma treatment.

IntroductionDiabetic nephropathy (DN), distinguished by detrimental changes in the renal glomeruli, is regarded as the leading cause of death from end-stage renal disease among diabetics. Cellular senescence plays a paramount role, profoundly affecting the onset and progression of chronic kidney disease (CKD) and acute kidney injuries. This study was designed to delve deeply into the pathological mechanisms between glomerulus-associated DN and cellular senescence.MethodsGlomerulus-associated DN datasets and cellular senescence-related genes were acquired from the Gene Expression Omnibus (GEO) and CellAge database respectively. By integrating bioinformatics and machine learning methodologies including the LASSO regression analysis and Random Forest, we screened out four signature genes. The receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic performance of the selected genes. Rigorous experimental validations were subsequently conducted in the mouse model to corroborate the identification of three signature genes, namely LOX, FOXD1 and GJA1. Molecular docking with chlorogenic acids (CGA) was further established not only to validate LOX, FOXD1 and GJA1 as diagnostic markers but also reveal their potential therapeutic effects.Results and discussionIn conclusion, our findings pinpointed three diagnostic markers of glomerulus-associated DN on the basis of cellular senescence. These markers could not only predict an increased risk of DN progression but also present promising therapeutic targets, potentially ushering in innovative treatments for DN in the elderly population.

Background: Chronic non-bacterial prostatitis (CNP), one of the most common chronic diseases in urology, leads to pain in the prostate and dysuria, critically affecting the physical or mental health of patients. However, there are no standard treatment approaches for the treatment of CNP in the clinic. Although the clinical application of Bushen Daozhuo granule (BSDZG) offers hope to CNP patients in China, the mechanisms of BSDZG in treating CNP are still not entirely clear. Hence, we aimed to investigate the novel therapeutic mechanisms of BSDZG on CNP.Methods: In this study, we first assayed the prostate index of rats and then determined the anti-inflammatory and anti-apoptotic effects of BSDZG on CNP in vivo and in vitro by employing ELISA kits and TUNEL staining. Next, we investigated whether the anti-inflammatory and anti-apoptotic mechanisms of BSDZG on prostate protein-induced rats and lipopolysaccharide (LPS) induced RWPE-1 cells were related to the AKT, p38 MAPK, and NF-κB pathways with the help of Western blot. Finally, the influence of BSDZG on the interaction between the p38 MAPK and NF-κB pathway in LPS-induced RWPE-1 cells was explored by adopting dehydrocorydaline (DHC, p38 MAPK activator) with the help of ELISA kits and Western blot.Results:In vivo, BSDZG effectively reduced the prostate index. In vivo and in vitro, BSDZG dramatically declined the level of two pro-inflammatory cytokines, TNF-α and IL-1β, as well as the apoptosis rate. Moreover, in vivo and in vitro, BSDZG memorably upregulated the expression level of p-AKT, and substantially downregulated the expression level of p-p38 MAPK and NF-κB2. The activation of p38 MAPK significantly reversed the moderation effects of BSDZG on the level of TNF-α and IL-1β, as well as the expression level of p-p38 MAPK and NF-κB2 in vitro.Conclusion: To sum up, the in vivo and in vitro therapeutic mechanisms of BSDZG on CNP were reflected as the anti-inflammation and anti-apoptosis that was formed by inhibiting the level of pro-inflammatory cytokines, TNF-α and IL-1β, to regulate the AKT, p38 MAPK, and NF-κB pathways, and the anti-inflammatory effect of BSDZG was realized by suppressing the p38 MAPK pathway to inhibit the downstream NF-κB pathway.

BackgroundTransnasal humidified rapid-insufflation ventilator exchange (THRIVE) has the characteristics of operating easily and maintaining oxygenation and eliminating CO2, which makes it possible to be used in endoscopic thoracic sympathectomy (ETS). The application of THRIVE in ETS remains undefined. The purpose of this randomized controlled study is to assess the efficacy between THRIVE and laryngeal mask airway (LMA) for ETS.MethodsIn total, 34 patients from May 2022 to May 2023 in Huazhong University of Science and Technology Union Shenzhen Hospital undergoing ETS were randomly divided into a THRIVE group (n = 17) and an LMA group (n = 17). A serial arterial blood gas analysis was conducted during the perioperative period. The primary outcome was the arterial partial pressure of carbon dioxide (PaCO2) during the perioperative period. The secondary outcome was arterial partial pressure of oxygen (PaO2) during the perioperative period.ResultsThe mean (SD) highest PaCO2 in the THRIVE group and LMA group were 99.0 (9.0) mmHg and 51.7 (5.2) mmHg, respectively (p

ObjectiveTo evaluate the efficacy and safety of Shenqi Fuzheng Injection (SFI) combined with platinum-based chemotherapy (PBC) for the treatment of advanced non-small cell lung cancer (NSCLC).MethodsSeven electronic databases, including CNKI and Wanfang, were comprehensively searched to screen randomized controlled trials (RCTs) until May 1, 2022. The quality of each trial was evaluated according to the Cochrane Handbook for Systematic Reviews of Interventions, and systematic reviews were conducted according to the PRISMA guidelines. Statistical analysis was performed using Review Manager 5.3, and the results were expressed as relative risk (RR) and 95% confidence interval (95% CI). The primary outcome measures were objective response rate (ORR) and disease control rate (DCR). The secondary outcome measures were quality of life and toxicity. Subgroup analysis was performed according to the number of days of SFI single-cycle treatment and combined PBC regimen.ResultsA total of 44 RCTs involving 3475 patients were included in the study. The meta-analysis results showed that, compared with PBC alone, SFI combined with PBC significantly improved the ORR (RR = 1.27, 95% CI = 1.18–1.37, P < 0.00001), DCR (RR = 1.12, 95% CI = 1.08–1.15, P < 0.00001), and quality of life (RR = 1.41, 95% CI = 1.31–1.52, P < 0.00001). It also reduced chemotherapy-induced hemoglobin reduction (RR = 0.57, 95% CI = 0.48–0.67, P < 0.00001), leukopenia (RR = 0.61, 95% CI = 0.53–0.71, P < 0.00001), thrombocytopenia (RR = 0.62, 95% CI = 0.55–0.70, P < 0.00001), and simple bone marrow suppression (RR = 0.55, 95% CI = 0.41–0.73, P < 0.0001). Nausea and vomiting (RR = 0.63, 95% CI = 0.52–0.77, P < 0.00001), diarrhea (RR = 0.48, 95% CI = 0.37–0.64, P < 0.00001), and simple digestive tract reactions (RR = 0.63, 95% CI = 0.49–0.80, P = 0.0002) also decreased with the treatment of SFI.ConclusionSFI combined with PBC for the treatment of advanced NSCLC improved the ORR, DCR, and quality of life, and reduced the incidence of myelosuppression and gastrointestinal adverse reactions. However, considering the limitations of existing evidence, further verification using high-quality RCTs is required.Systematic review registrationhttps://inplasy.com/inplasy-2022-7-0026, identifier INPLASY202270026.

Introduction: Economic development is not simply the accumulation of elements, but the improvement of efficiency, which is supported by infrastructure construction. In particular, the urban green and smart development (UGSD) in recent years has put forward higher requirements for infrastructure, and domestic trade as well as opening-up are of great significance during the process.Methods: Based on the panel data of 221 prefecture-level cities in China from the year of 2005 to 2019, this paper adopts the undesirable SBM model and GML index to measure the level of UGSD. Then the spatial Durbin model is conducted to explore the direct spatial spillover effects and the spatial decomposition effects of energy, transportation, and information infrastructure on UGSD. Considering the context of dual cycle, the indirect effects of domestic trade and opening-up between infrastructures and UGSD are further analyzed.Results: Results show that UGSD demonstrates strong spatial agglomeration and maintains a stable spatial positive correlation with different spatial matrices. In general, energy and transportation infrastructure show positive spatial spillover effects on UGSD. By contrast, information infrastructure presents positive spatial spillover effect on UGSD on the whole, while shows insignificant and negative spatial spillover effect with geographical distance matrix. Furthermore, the mediation effect indicates that both transportation and information infrastructure mainly promote local and adjacent cities’ UGSD through domestic trade with economic distance matrix. By contrast, energy infrastructure exerts positive spatial spillover effect on UGSD through weakening the negative impact of opening-up.Discussion: The conclusions of the research show that it is necessary to construct infrastructure in a reasonable way, strengthen the positive spillover effect of intercity factors, and promote the two-wheel driving effect of domestic trade and opening-up on the relationship between infrastructure and UGSD.

Infantile fibrosarcoma (IFS) is a rare tumor in childhood characterized by a single, localized, painless mass that grows rapidly but has a relatively indolent biological behavior and a favorable prognosis. Eighty-five percent of infantile fibrosarcomas are associated with t (12;15) (p13;25) chromosomal translocation resulting in ETV6-NTRK3 gene fusion, which provides the target for targeted therapy. Here, we report a case of IFS in a newborn with a mass in the left lower extremity confirmed by imaging, histopathological examination, tissue FISH testing, and high-throughput sequencing to detect gene rearrangement. Based on gene fusion targeted drug testing results, the patient was treated with standard doses of larotrectinib, resulting in significant mass shrinkage with no adverse effects, demonstrating the treatment effect of targeted therapy. This case provides a reference for using larotrectinib in newborns with IFS.

This contribution presents an assessment at a regional (island) scale of the beach erosion due to storm events under Climate Change. The approach adopted to assess beach erosion at the island scale consisted of three modules. First, the location, dimensions and other attributes of the Cypriot beaches were recorded on the basis of widely-available satellite imagery. Secondly, sea levels and waves were modeled along the coast under different climatic scenarios and dates in the 21st century. Finally, using these projections beach retreat due to the relative mean sea level rise (RSLR) and extreme sea levels (ESLs) was estimated using ensembles of analytical and numerical cross-shore morphodynamic models, respectively. Extreme sea levels (ESLs) were projected to (a) increase by up to 60% in 2100 from their baseline (2000) levels, and (b) vary along the coast, with the highest ESLs (and corresponding waves) projected for the southern and western coasts. The mostly narrow Cypriot beaches (91% recorded maximum widths of < 50 m) showed increased exposure to erosion. In 2100, about 47% and 72% (based on the median model estimates) of the 241 unprotected Cypriot beaches will be permanently eroded, due to mean sea level rise (SLR), to 50% of their present maximum width, depending on the scenario. In addition to the long-term erosion due to SLR, severe storm erosion is projected by 2050 even under the RCP4.5 scenario; the 100-year extreme sea level event (ESL100) may overwhelm (at least temporarily) 49% of the currently unprotected Cypriot beaches without effective adaptation responses, with the most exposed beaches located along the northern coast. As the beach carrying capacity and hedonic value will be severely compromised, effective adaptation policies and technical measures will be urgently required.

Objective: Traditional Chinese medicine (TCM) has been used as a complementary treatment for cancer patients, but there has been no quantitative comprehensive analysis of TCM’s efficacy. The purpose of this paper is to explore the current status and hotspots of TCM in cancer research from 2002 to 2022 and to provide a reference for future research.Methods: We retrieved articles published between 2002 and 2022 from the Web of Science database and analyzed them using R software, VOSviewer, and CiteSpace software.Results: A total of 7,129 articles were included in this study. The publication rate of TCM cancer research increased steadily from 2002 to 2022, with a rapid increase from 2010 to 2021. China was the country with the most published articles, followed by the United States, Republic of Korea, Germany, and Japan. China was also the country with the most international collaborations, and China Medical University and Shanghai University of Traditional Chinese Medicine were the most representative cooperation centers. The Journal of Ethnopharmacology was the most published and cited journal. Apoptosis, expression, in vitro, activation, and other related keywords were commonly used in these articles. Breast cancer, colorectal cancer, gastric cancer, liver cancer, and lung cancer were the most studied cancer types in TCM research. Pathway-related apoptosis, anti-inflammation, and oxidative stress were the hotspots and trends of TCM’s anti-cancer mechanism. Metabolomics combined with network pharmacology was the main research method.Conclusion: Traditional Chinese medicine as an anti-cancer drug has received increasing attention from researchers worldwide, and it is expected to be a hotspot for developing new anti-cancer drugs in the future. Our study provides a comprehensive analysis of the current status and hotspots of TCM cancer research, which could serve as a valuable reference for future studies.

Objective: The aim of this investigation was to explore the correlation between the levels of tumor-infiltrating CD8+ and CD4+ T cells and the quantitative pharmacokinetic parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with advanced gastric cancer.Methods: We retrospectively analyzed the data of 103 patients with histopathologically confirmed advanced gastric cancer (AGC). Three pharmacokinetic parameters, Kep, Ktrans, and Ve, and their radiomics characteristics were obtained by Omni Kinetics software. Immunohistochemical staining was used to determine CD4+ and CD8+ TILs. Statistical analysis was subsequently performed to assess the correlation between radiomics characteristics and CD4+ and CD8+ TIL density.Results: All patients included in this study were finally divided into either a CD8+ TILs low-density group (n = 51) (CD8+ TILs < 138) or a high-density group (n = 52) (CD8+ TILs ≥ 138), and a CD4+ TILs low-density group (n = 51) (CD4+ TILs < 87) or a high-density group (n = 52) (CD4+ TILs ≥ 87). ClusterShade and Skewness based on Kep and Skewness based on Ktrans both showed moderate negative correlation with CD8+ TIL levels (r = 0.630–0.349, p < 0.001), with ClusterShade based on Kep having the highest negative correlation (r = −0.630, p < 0.001). Inertia-based Kep showed a moderate positive correlation with the CD4+ TIL level (r = 0.549, p < 0.001), and the Correlation based on Kep showed a moderate negative correlation with the CD4+ TIL level, which also had the highest correlation coefficient (r = −0.616, p < 0.001). The diagnostic efficacy of the above features was assessed by ROC curves. For CD8+ TILs, ClusterShade of Kep had the highest mean area under the curve (AUC) (0.863). For CD4+ TILs, the Correlation of Kep had the highest mean AUC (0.856).Conclusion: The radiomics features of DCE-MRI are associated with the expression of tumor-infiltrating CD8+ and CD4+ T cells in AGC, which have the potential to noninvasively evaluate the expression of CD8+ and CD4+ TILs in AGC patients.

PurposeTo describe neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser treatment of visual axis opacification and secondary membranes in pediatric patients with cataracts under intranasal dexmedetomidine sedation.MethodsTwenty eyes of 17 patients with secondary membrane formation after cataract extraction were enrolled in this study. Intranasal dexmedetomidine sedation (3 ug/kg) was administered, and Nd:YAG laser (Ellex Super Q, Adelaide, Australia) procedures were performed with children in the sitting position with their chin supported on a laser delivery slit lamp. Preoperative and postoperative visual acuities were documented, and medical records were reviewed.ResultsThe age of the patients ranged from 5 to 83 months (31.82 ± 27.73). Nineteen (95.0%) eyes had congenital cataracts and one (5.0%) had a traumatic cataract. Nd:YAG laser treatment of VAO with ten (50.0%) eyes, pupillary membranes with three (15.0%) eyes, pupillary cortical proliferation with six (30.0%) eyes, and anterior capsule contraction with one (5.0%) eye. Five (25.0%) eyes demonstrated visual acuity improvement, whereas six (30.0%) eyes remained unchanged after laser treatment. The recurrence rate was 30.0% and four eyes underwent a second Nd:YAG membranectomy. No side effects or tolerances due to sedative drugs were observed.ConclusionNd:YAG laser membranectomy under intranasal dexmedetomidine sedation was safely performed in children as young as 5 months old in a sitting position. This approach facilitates patient convenience, doctor proficiency, and cost reductions. Patients with recurrence can be treated by repeating the procedure.

IntroductionCommon prosperity is a major research project in China, and the scientific measurement and evaluation of common prosperity is very important.MethodsIn this study, firstly, we construct a comprehensive evaluation index system for the common prosperity level (CPL). We then develop an evaluation model of CPL based on prospect theory, probabilistic linguistic ordered weighted distance measure, and the TOPSIS method, wherein we use a probabilistic linguistic term set (PLTS) to describe the uncertainty and complexity of the assessment process. Above all, we use prospect theory to reflect the preferences of experts to meet the unique needs for the evaluation of common prosperity. Moreover, we apply the proposed evaluation index system and model to evaluate the CPL of Zhejiang Province, China's first common prosperity demonstration zone, as an example to conduct relevant research. The advantages and effectiveness of the proposed method are verified by the sensitivity and comparative analysis.ResultsThe findings prove that the application of the new PLTS evaluation framework in CPL assessment is robust.DiscussionWe propose specific suggestions for improving the development of common prosperity.

PurposeTo explore the effect of corneal spherical aberration on the visual acuity and visual quality of eyes implanted with the TECNIS Symfony intraocular lens (IOL).MethodsA total of 43 patients with age-related cataract (60 eyes) undergoing phacoemulsification and TECNIS Symfony IOL implantation were enrolled in this study. The uncorrected distance (UDVA), intermediate (UIVA), near visual acuity (UNVA), corrected distance visual acuity (CDVA), contrast sensitivity, and ocular spherical aberration were recorded 3 months after surgery. Preoperative and postoperative corneal spherical aberration were also measured using the iTrace device. Objective scattering index (OSI), modulation transfer function cut-off frequency (MTF cut-off), and Strehl ratio (SR) were measured by the Optical Quality Analyzing System. Catquest-9SF questionnaire were applied too. Spearman’s correlation analysis was used to evaluate the relationship between spherical aberration and visual quality parameters.ResultsPatients were satisfied with their postoperatively visual quality. And the postoperative logMAR UDVA, UIVA, UNVA, and CDVA was 0.05 ± 0.07, 0.04 ± 0.06, 0.15 ± 0.07, and 0.03 ± 0.05, respectively. The mean preoperative corneal spherical aberration was 0.24 ± 0.10 μm, which is the only factor influencing postoperatively UNVA, and it was negatively correlated with UNVA and glare contrast sensitivity under 18 cpd (cycle/degree, cpd) spatial frequency (r = −0.403, −0.300, −0.360; all P < 0.05). Additionally, the greater the residual spherical aberration of the cornea, the better the near vision after operation. The mean postoperative ocular spherical aberration was −0.03 ± 0.07 μm, it was not correlated with visual acuity, contrast sensitivity, and visual quality (all P > 0.05).ConclusionPreoperative positive spherical aberration can benefit near vision while decrease contrast sensitivities at high spatial frequencies when implanted with the TECNIS Symfony IOL.

AimTo observe the change of capsulotomy opening diameter (COD) in aphakic eyes after primary congenital cataract removal and investigate its influencing factors.MethodsOcular parameters, including corneal diameter (CD), axial length (AL), anterior and posterior COD (ACOD, PCOD), and age at surgery were recorded at primary congenital cataract removal and secondary intraocular lens implantation. The concentrations of 15 kinds of cytokines in aqueous humor samples collected at the primary surgery were detected. The change (Δ) of COD between two surgeries were described, and its association was analyzed.ResultsFifty eyes from 33 patients with congenital cataract who underwent primary and secondary surgery were enrolled. The changes in ACOD and PCOD were not statistically significant on the whole. ΔACOD was positively correlated with ΔCD and the concentrations of PDGF-AA, VEGF and TGF-β1. The concentration of FGF-2 and the interval between two surgeries showed negative correlations with ΔACOD and ΔPCOD.ConclusionCOD in aphakic eyes kept changing after primary surgery. The positive correlation between ΔACOD and ΔCD manifested the enlargement of ACOD was influenced by lateral eye growth. Meanwhile, ΔACOD was also associated with cytokines, indicating postoperative inflammation promoted the ACOD constriction.

Many drugs have been shown to be metabolized by the human gut microbiome, but probiotic-driven drug-metabolizing capacity is rarely explored. Here, we developed an integrated metabolomics, culturomics, and bionics framework for systematically studying probiotics-driven drug metabolism. We discovered that 75% (27/36 of the assayed drugs) were metabolized by five selected probiotics, and drugs containing nitro or azo groups were more readily metabolized. As proof-of-principle experiments, we showed that Lacticaseibacillus casei Zhang (LCZ) could metabolize racecadotril to its active products, S-acetylthiorphan and thiorphan, in monoculture, in a near-real simulated human digestion system, and in an ex vivo fecal co-culture system. However, a personalized effect was observed in the racecadotril-metabolizing activity of L. casei Zhang, depending on the individual’s host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among L. casei Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics.

Chemical composition of sediments is often used to evaluate paleoclimate condition, provenance, tectonic setting, depositional condition, and paleoproductivity. However, the validity of these proxies has long been questioned. The comprehensive use of organic and inorganic multi-indicators in combination when interpreting issues related to terrestrial shales should be advocated. The paleodepositional environment, origin of organic matter (OM) and factor controlling OM accumulation in the Early Jurassic Badaowan (J1b) and Sangonghe (J1s) as well as Middle Jurassic Xishanyao (J2x) lacustrine shales in the East Fukang Sag are reassessed by using organic geochemical characteristics of the OM. Some previous knowledge is updated, and some knowledge is further supported by more evidence. The typical clay-rich shale developed under a lacustrine sedimental environment, and the thermal maturity of these organic-rich shales has entered the oil window and formed economic hydrocarbon potential for the tight-oil and shale-oil reservoirs. The paleoclimate conditions of the study area were warm and humid from the Early to Middle Jurassic periods but were colder and drier after the Middle Jurassic period. The salinity of the water column ranged from freshwater to brackish conditions. The J2x Formation was deposited under oxic conditions, while J1b and J1s formations developed under suboxic and reducing environmental conditions. The J2x Formation OM mainly derived from higher plants was deposited in a terrestrial environment,while the OM of J1b and J1s formations was a mixed OM derived from higher plants and bacteria with little algae deposited under bay/estuary environments alternated with terrestrial environments. It is effective to reflect the paleoclimate by element index and judge the salinity by the updated element thresholds, but it is not effective to evaluate the paleoredox conditions by common elemental ratios and to evaluate the paleoproductivity by Ba in the study area.

Accumulation and activation of immunocytes in adipose tissues are essential to obesity-induced inflammation and insulin resistance. Chemokines are pivotal for the recruitment of immunocytes in adipose tissue during obesity. Chemokine (C-C motif) ligand 5 (CCL5) plays a vital role in the recruitment of immunocytes to sites of inflammation. CCL5 expression level is increased in obese adipose tissue from humans and mice. However, the role of CCL5 in obesity-induced adipose inflammation remains unclear. Our study found that the CCL5 expression level was increased in the epididymal white adipose tissue (eWAT) of obese mice, particularly in CD8+ T cells. CCL5 knockout (KO) mice exhibited better glucose tolerance than wild-type (WT) mice under lean conditions. In contrast, CCL5 KO mice were more insulin resistant and had severe hepatic steatosis than WT mice under obese conditions. Increased T cells in adipose tissue heaven adipose inflammation in obese CCL5 KO mice. The compensatory increased T cell-associated chemokines may account for increased T cell content in the eWAT of obese CCL5 KO mice. These findings imply that CCL5 deficiency exacerbates adipose inflammation and impairs insulin sensitivity in the metabolic tissues of obese mice.

Intracerebral hemorrhage (ICH) is one common yet devastating stroke subtype, imposing considerable burdens on families and society. Current guidelines are limited to symptomatic treatments after ICH, and the death rate remains significant in the acute stage. Thus, it is crucial to promote research to develop new targets on brain injury after ICH. In response to hematoma formation, amounts of chemokines are released in the brain, triggering the infiltration of resident immune cells in the brain and the chemotaxis of peripheral immune cells via the broken blood–brain barrier. During the past decades, mounting studies have focused on the roles of chemokines and their receptors in ICH injury. This review summarizes the latest advances in the study of chemokine functions in the ICH. First, we provide an overview of ICH epidemiology and underlying injury mechanisms in the pathogenesis of ICH. Second, we introduce the biology of chemokines and their receptors in brief. Third, we outline the roles of chemokines in ICH according to subgroups, including CCL2, CCL3, CCL5, CCL12, CCL17, CXCL8, CXCL12, and CX3CL1. Finally, we summarize current drug usage targeting chemokines in ICH and other cardio-cerebrovascular diseases. This review discusses the expressions of these chemokines and receptors under normal or hemorrhagic conditions and cell-specific sources. Above all, we highlight the related data of these chemokines in the progression and outcomes of the ICH disease in preclinical and clinical studies and point to therapeutic opportunities targeting chemokines productions and interactions in treating ICH, such as accelerating hematoma absorption and alleviating brain edema.

Recently, personality trait recognition, which aims to identify people’s first impression behavior data and analyze people’s psychological characteristics, has been an interesting and active topic in psychology, affective neuroscience and artificial intelligence. To effectively take advantage of spatio-temporal cues in audio-visual modalities, this paper proposes a new method of multimodal personality trait recognition integrating audio-visual modalities based on a hybrid deep learning framework, which is comprised of convolutional neural networks (CNN), bi-directional long short-term memory network (Bi-LSTM), and the Transformer network. In particular, a pre-trained deep audio CNN model is used to learn high-level segment-level audio features. A pre-trained deep face CNN model is leveraged to separately learn high-level frame-level global scene features and local face features from each frame in dynamic video sequences. Then, these extracted deep audio-visual features are fed into a Bi-LSTM and a Transformer network to individually capture long-term temporal dependency, thereby producing the final global audio and visual features for downstream tasks. Finally, a linear regression method is employed to conduct the single audio-based and visual-based personality trait recognition tasks, followed by a decision-level fusion strategy used for producing the final Big-Five personality scores and interview scores. Experimental results on the public ChaLearn First Impression-V2 personality dataset show the effectiveness of our method, outperforming other used methods.

The accurate detection and segmentation of apples during growth stage is essential for yield estimation, timely harvesting, and retrieving growth information. However, factors such as the uncertain illumination, overlaps and occlusions of apples, homochromatic background and the gradual change in the ground color of apples from green to red, bring great challenges to the detection and segmentation of apples. To solve these problems, this study proposed an improved Mask Scoring region-based convolutional neural network (Mask Scoring R-CNN), known as MS-ADS, for accurate apple detection and instance segmentation in a natural environment. First, the ResNeSt, a variant of ResNet, combined with a feature pyramid network was used as backbone network to improve the feature extraction ability. Second, high-level architectures including R-CNN head and mask head were modified to improve the utilization of high-level features. Convolutional layers were added to the original R-CNN head to improve the accuracy of bounding box detection (bbox_mAP), and the Dual Attention Network was added to the original mask head to improve the accuracy of instance segmentation (mask_mAP). The experimental results showed that the proposed MS-ADS model effectively detected and segmented apples under various conditions, such as apples occluded by branches, leaves and other apples, apples with different ground colors and shadows, and apples divided into parts by branches and petioles. The recall, precision, false detection rate, and F1 score were 97.4%, 96.5%, 3.5%, and 96.9%, respectively. A bbox_mAP and mask_mAP of 0.932 and 0.920, respectively, were achieved on the test set, and the average run-time was 0.27 s per image. The experimental results indicated that the MS-ADS method detected and segmented apples in the orchard robustly and accurately with real-time performance. This study lays a foundation for follow-up work, such as yield estimation, harvesting, and automatic and long-term acquisition of apple growth information.

We analyze bacterial composition, diversity, geographical distribution, and their community networks in lake water in three adjacent regions on the Qinghai-Tibet Plateau (QTP). Results show that bacterial alpha-diversity indices are much lower in the Hoh Xil (HX) than that in the Yellow River Headwater (YRH) regions and the Qaidam (QD) region. The dominant phyla in QD and YRH are Proteobacteria which account for 42.45 % and 43.64 % of all detected phyla, while Bacteroidetes is the dominant bacterial taxa in HX (46.07 %). Redundancy analysis results suggest that the most important factors in driving bacterial community composition in the three regions are altitude (QD), total nitrogen (YRH), and pH (HX), respectively. Both environmental factors and spatial factors significantly affect the bacterial community composition in QD and HX, while only environmental factors are the major drivers in YRH. Finally, network analyses reveal that the bacterial network structure in QD is more complex than those in YRH and HX, whereas the bacterial network in HX is the most stable, followed by those in QD and YRH.

Vaginal adhesions and stenosis are infrequent long-term sequelae following pediatric pelvic fractures. Patients may not present with signs and symptoms before menarche, leading to delayed diagnosis and treatment. We report an adolescent girl who presented with a post-abdominal trauma pelvic fracture and urethrovaginal fistula and subsequent severe vaginal adhesion, which resulted in infection and obstructive symptoms after menarche. Hysteroscopy-guided vaginal adhesion release using an epidural catheter and ultrasonography was performed, followed by vaginal dilation, to resolve obstructive symptoms. For girls with pelvic fractures, education on possible long-term sequelae is required, as is regular follow-up. Timely diagnosis and treatment are important, and hysteroscopic release of vaginal adhesion and postoperative regular vaginal dilation may be an effective treatment.

Deficit schizophrenia (DS) patient is a homogenous subtype of schizophrenia that includes primary and enduring negative symptoms. This study aimed to compare the differences in cognitive functioning and plasma levels of C-reactive protein (CRP) and inflammatory cytokines among DS patients, nondeficit schizophrenia (NDS) patients, and healthy controls (HCs). A total of 141 schizophrenia patients and 67 HCs were included in this study. The schizophrenia patients were divided into DS (N= 51) and NDS (N=90) groups based on the Proxy for the Deficit Syndrome Scale (PDS). The Positive and Negative Syndrome Scale (PANSS) and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) were used to evaluate the clinical symptoms and cognitive performances, respectively. The plasma level of CRP, IL-1β, Il-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, TNF-α, and IFN-γ were measured using enzyme-linked immunosorbent assays (ELISAs). Our results showed that DS patients had the worst cognitive performance, especially in the immediate memory, attention, and language dimensions, compared to the NDS and HC groups. Compared to the HCs group, DS patients had higher levels of CRP, IL-1β, IL-6, IL-8, IFN-γ, and total proinflammatory cytokines, and NDS patients had higher levels of IL-1β, IFN-γ, and proinflammatory cytokines. We also found that CRP levels were significantly increased in DS patients compared to NDS patients. Moreover, stepwise logistic regression analysis revealed that CRP is an independent risk factor for DS. Sex stratification analysis showed significant differences in almost all cytokines in female samples but not in male samples. The significant differences in cognitive performance and inflammatory components among groups suggest that deficit syndrome is an independent endophenotype of schizophrenia patients with unique immune-inflammatory features, but may have sex characteristics.

Necroptosis, which is recently recognized as a form of programmed cell death, plays a critical role in cancer biology, including tumorigenesis and cancer immunology. It was recognized not only to defend against tumor progression by suppressing adaptive immune responses but also to promote tumorigenesis and cancer metastasis after recruiting inflammatory responses. Thus the crucial role of necrosis in tumorigenesis has attracted increasing attention. Due to the heterogeneity of the tumor immune microenvironment (TIME) in lung adenocarcinoma (LUAD), the prognosis and the response to immunotherapy vary distinctly across patients, underscoring the need for a stratification algorithm for clinical practice. Although previous studies have formulated the crucial role of lncRNAs in tumorigenicity, the relationship between necroptosis-related lncRNAs, TIME, and the prognosis of patients with LUAD was still elusive. In the current study, a robust and novel prognostic stratification model based on Necroptosis-related LncRNA Risk Scoring (NecroLRS) and clinicopathological parameters was constructed and systemically validated in both internal and external validation cohorts. The expression profile of four key lncRNAs was further validated by qRT-PCR in 4 human LUAD cell lines. And a novel immune landscape alteration was observed between NecroLRS-High and -Low patients. To further elucidate the mechanism of necroptosis in the prognosis of LUAD from a single-cell perspective, a novel stratification algorithm based on K-means clustering was introduced to extract both malignant and NecroLRS-High subsets from epithelial cells. And the necroptosis-related immune infiltration landscape and developmental trajectory were investigated respectively. Critically, NecroLRS was found to be positively correlated with neutrophil enrichment, inflammatory immune response, and malignant phenotypes of LUAD. In addition, novel ligand-receptor pairs between NecroLRS-High cells and other immunocytes were investigated and optimal therapeutic compounds were screened to provide potential targets for future studies. Taken together, our findings reveal emerging mechanisms of necroptosis-induced immune microenvironment alteration on the deteriorative prognosis and may contribute to improved prognosis and individualized precision therapy for patients with LUAD.

Background and purposeStudies showed that patients with hemorrhagic stroke are at a higher risk of developing deep vein thrombosis (DVT) than those with ischemic stroke. We aimed to develop a risk score (intracerebral hemorrhage-associated deep vein thrombosis score, ICH-DVT) for predicting in-hospital DVT after ICH.MethodsThe ICH-DVT was developed based on the Beijing Registration of Intracerebral Hemorrhage, in which eligible patients were randomly divided into derivation (60%) and internal validation cohorts (40%). External validation was performed using the iMCAS study (In-hospital Medical Complication after Acute Stroke). Independent predictors of in-hospital DVT after ICH were obtained using multivariable logistic regression, and β-coefficients were used to generate a scoring system of the ICH-DVT. The area under the receiver operating characteristic curve (AUROC) and the Hosmer–Lemeshow goodness-of-fit test were used to assess model discrimination and calibration, respectively.ResultsThe overall in-hospital DVT after ICH was 6.3%, 6.0%, and 5.7% in the derivation (n = 1,309), internal validation (n = 655), and external validation (n = 314) cohorts, respectively. A 31-point ICH-DVT was developed from the set of independent predictors including age, hematoma volume, subarachnoid extension, pneumonia, gastrointestinal bleeding, and length of hospitalization. The ICH-DVT showed good discrimination (AUROC) in the derivation (0.81; 95%CI = 0.79–0.83), internal validation (0.83, 95%CI = 0.80–0.86), and external validation (0.88; 95%CI = 0.84–0.92) cohorts. The ICH-DVT was well calibrated (Hosmer–Lemeshow test) in the derivation (P = 0.53), internal validation (P = 0.38), and external validation (P = 0.06) cohorts.ConclusionThe ICH-DVT is a valid grading scale for predicting in-hospital DVT after ICH. Further studies on the effect of the ICH-DVT on clinical outcomes after ICH are warranted.

BackgroundFulminant myocarditis (FM) is an inflammatory process of the myocardium and an important cause of cardiac dysfunction in children; it is characterized by rapid onset, acute progression, and high mortality. The study sought to describe the clinical characteristics and prognostic factors in children with FM.MethodsThe study population consists of 37 consecutive patients admitted from May 2014 to December 2021 with a diagnosis of FM. According to the prognosis of children with FM during hospitalization, they were divided into “survival” group (25 cases) and “death” group (12 cases). A multivariate logistic regression analysis was performed to identify the independent predictors of in-hospital mortality in the patients, and receiver operating characteristic (ROC) curve was used to explore the predictive value of related factors.ResultsThe 37 children with FM had an average age of 8.35 ± 4.36 years old. Twenty-five of the patients survived and 12 died. Twenty-five of the children were discharged from the hospital after a series of active rescue treatments such as nutritional myocardial drugs, high-dose intravenous immunoglobulin (IVIG), glucocorticoids (GCs), temporary pacemaker (TP), extracorporeal membrane oxygenation (ECMO), and continuous renal replacement therapy (CRRT).Twelve of the children were classified into the death group because the resuscitation failed. The levels of procalcitonin (PCT), creatine kinase (CK), and myoglobin (MYO) in the death group were all higher than in the survival group (all P < 0.05), and the left ventricular ejection fraction (LVEF) in the death group was significantly lower than in the survival group (P = 0.002). The binary logistic regression analysis revealed that MYO [OR:1.006; 95%CI:(1–1.012); P = 0.045] and LVEF [OR: 0.876; 95% CI: (0.785–0.978); P = 0.019] were independent predictors of FM. ROC curve analysis showed that the area under ROC curve (AUC) of MYO and LVEF was [AUC:0.957; 95%CI:0.897~1] and [AUC:0.836; 95%CI:0.668~1], and the area under the combined ROC curve for MYO + LVEF was significantly higher than that for MYO or LVEF alone (P < 0.05), indicating that the MYO + LVEF combined diagnosis had a higher predictive value for FM.ConclusionThe levels of MYO and LVEF can be markers for prognosis of FM and can effectively evaluate the disease severity. Their combination can improve forecast accuracy; thus, the detection of the above-mentioned indexes possesses a higher value for clinical applications.

Enhanced recovery after surgery (ERAS) can accelerate patient recovery. However, little research has been done on optimizing the ERAS-related measures and how the measures interact with each other. The Bayesian network (BN) is a graphical model that describes the dependencies between variables and is also a model for uncertainty reasoning. In this study, we aimed to develop a method for optimizing anesthetic decisions in ERAS and then investigate the relationship between anesthetic decisions and outcomes. First, assuming that the indicators used were independent, the effects of combinations of single indicators were analyzed based on BN. Additionally, the impact indicators for outcomes were selected with statistical tests. Then, based on the previously selected indicators, the Bayesian network was constructed using the proposed structure learning method based on Strongly Connected Components (SCC) Local Structure determination by Hill Climbing Twice (LSHCT) and adjusted according to the expert’s knowledge. Finally, the relationship is analyzed. The proposed method is validated by the real clinical data of patients with benign gynecological tumors from 3 hospitals in China. Postoperative length of stay (LOS) and total cost (TC) were chosen as the outcomes. Experimental results show that the ERAS protocol has some pivotal indicators influencing LOS and TC. Identifying the relationship between these indicators can help anesthesiologists optimize the ERAS protocol and make individualized decisions.

Low temperatures in the spring often lead to a decline in the emergence rate and uniformity of maize, which can affect yield in northern regions. This study used 365 recombinant inbred lines (RILs), which arose from crossing Qi319 and Ye478, to identify low-temperature resistance during the germination stage by measuring eight low-temperature-related traits. The quantitative trait locis (QTLs) were mapped using R/qtl software by combining phenotypic data, and the genotyping by sequencing (GBS) method to produce a high-density genetic linkage map. Twenty QTLs were detected during QTL mapping, of which seven QTLs simultaneously detected a consistent 197.10–202.30 Mb segment on chromosome 1. The primary segment was named cQTL1-2, with a phenotypic variation of 5.18–25.96% and a physical distance of 5.2 Mb. This combines the phenotype and genotype with the identification of seven chromosome segment substitution lines (CSSLs), which were derived from Ye478*Qi319 and related to cQTL1-2. The physical distance of cQTL1-2 was reduced to approximately 1.9 Mb. The consistent meta-QTL mQTL1 was located at 619.06 cM on chromosome 1, had a genetic distance of 7.27 cM, and overlapped with cQTL1-2. This was identified by combining the results of previous QTL studies assessing maize tolerance to low temperatures at the germination stage. An assessment of the results of the RIL population, CSSLs, and mQTL1 found the consistent QTL to be LtQTL1-1. It was identified in bin1.06-1.07 at a confidence interval of between 200,400,148 and 201,775,619 bp. In this interval, qRT-PCR found that relative expression of the candidate genes GRMZM2G082630 and GRMZM2G115730 were both up-regulated in low-temperature tolerant lines and down-regulated in sensitive lines (P < 0.01).

BackgroundBreast cancer (BC) is one of the most common malignant tumors in women and poses a serious threat to their health. Compound Kushen injection (CKI) has shown therapeutic effects on a variety of cancers, including BC, and it can significantly improve the lives of patients. However, the underlying mechanism remains unclear and needs to be fully elucidated.MethodsThe active constituents of CKI were identified through a literature review, and the anti-BC targets of CKI were determined using multiple databases and a ChIP data analysis. Subsequently, the target was analyzed on the DAVID database through GO and KEGG to identify the key pathway that CKI affects to exhibit anti-BC activity. In addition, MCF-7 and MDA-MB-231 cells were treated with CKI for 24 and 48 hours at five concentrations, and the effects of CKI on cell proliferation and apoptosis were measured using MTT and annexin V/propidium iodide staining assays, respectively. The genes and protein identified to be involved in this pathway were verified using real-time quantitative PCR (qPCR) and western blot(WB) in BC cells.ResultsTwelve CKI anti-BC targets were obtained by a comprehensive analysis of the targets collected in the databases and results from the ChIP analysis. Bioinformatics analysis was performed for 12 targets. KEGG analysis showed that the 12 targets were mainly related to the VEGF, ErbB, and TNF signaling pathways. We focused our study on the VEGF signaling pathway as the p-value for the VEGF signaling pathway was the lowest among the three pathways. In vitro experiments showed that CKI significantly inhibited the proliferation of BC cells and induced apoptosis. Furthermore, qPCR and WB experiments showed that the expression of VEGF signaling pathway genes PIK3CA and NOS3 were significantly increased meanwhile SRC was significantly decreased after CKI intervention.ConclusionCKI significantly inhibited the proliferation of BC cells and induced apoptosis. The main mechanism for the anti-BC effect of CKI may be that it regulates the VEGF signaling pathway by increasing the expression of PIK3CA, SRC, and NOS3. Macrozamin and lamprolobine may be the main active components of CKI against BC.

In the past decade, two-dimensional (2D) materials and spintronic materials have been rapidly developing in recent years. 2D spin-gapless semiconductors (SGSs) are a novel class of ferromagnetic 2D spintronic materials with possible high Curie temperature, 100% spin-polarization, possible one-dimensional or zero-dimensional topological signatures, and other exciting spin transport properties. In this mini-review, we summarize a series of ideal 2D SGSs in the last 3 years, including 2D oxalate-based metal-organic frameworks, 2D single-layer Fe2I2, 2D Cr2X3 (X = S, Se, and Te) monolayer with the honeycomb kagome (HK) lattice, 2D CrGa2Se4 monolayer, 2D HK Mn–cyanogen lattice, 2D MnNF monolayer, and 2D Fe4N2 pentagon crystal. The mini-review also discusses the unique magnetic, electronic, topological, and spin-transport properties and the possible application of these 2D SGSs. The mini-review can be regarded as an improved understanding of the current state of 2D SGSs in recent 3 years.

Crohn’s disease (CD), as one of the principal form of inflammatory bowel disease (IBD), is characterized by the chronic and recurring inflammatory conditions in the intestine resulting from the over-activation of intestinal immunity. Hyposplenism is strongly associated with CD, while the effect of human spleen on the differentiation and development of immune cell subsets in CD patients remains unclear. Isolated congenital asplenia (ICA) is an extremely rare condition characterized by the absence of a spleen at birth without any other developmental defects. Here, we describe the first case of a patient with both ICA and CD, and follow the progression of CD from remission to active stage. Using cytometry by time of flight (CyTOF) analysis, we draw the first single-cell mapping of peripheral blood mononuclear cells (PBMC) from this unique patient, tracing back to the innate or adaptive immune cell subsets and cell surface markers affected by the spleen. Based on our analysis, it is speculated that the spleen contributes to maintaining immune homeostasis, alleviating intestinal inflammation and improving prognosis by influencing the differentiation and development of peripheral immune cell subsets and the expression of cell surface markers in patients with CD.

Traditional video recommendation provides the viewers with customized media content according to their historical records (e.g., ratings, reviews). However, such systems tend to generate terrible results if the data is insufficient, which leads to a cold-start problem. An affective video recommender system (AVRS) is a multidiscipline and multimodal human-robot interaction (HRI) system, and it incorporates physical, physiological, neuroscience, and computer science subjects and multimedia resources, including text, audio, and video. As a promising research domain, AVRS employs advanced affective analysis technologies in video resources; therefore, it can solve the cold-start problem. In AVRS, the viewers’ emotional responses can be obtained from various techniques, including physical signals (e.g., facial expression, gestures, and speech) and internal signals (e.g., physiological signals). The changes in these signals can be detected when the viewers face specific situations. The physiological signals are a response to central and autonomic nervous systems and are mostly involuntarily activated, which cannot be easily controlled. Therefore, it is suitable for reliable emotion analysis. The physical signals can be recorded by a webcam or recorder. In contrast, the physiological signals can be collected by various equipment, e.g., psychophysiological heart rate (HR) signals calculated by echocardiogram (ECG), electro-dermal activity (EDA), and brain activity (GA) from electroencephalography (EEG) signals, skin conductance response (SCR) by a galvanic skin response (GSR), and photoplethysmography (PPG) estimating users’ pulse. This survey aims to provide a comprehensive overview of the AVRS domain. To analyze the recent efforts in the field of affective video recommendation, we collected 92 relevant published articles from Google Scholar and summarized the articles and their key findings. In this survey, we feature these articles concerning AVRS from different perspectives, including various traditional recommendation algorithms and advanced deep learning-based algorithms, the commonly used affective video recommendation databases, audience response categories, and evaluation methods. Finally, we conclude the challenge of AVRS and provide the potential future research directions.

ObjectiveLow-density lipoprotein receptor-related protein-1 (LRP-1) and survivin are associated with radiotherapy resistance in patients with locally advanced rectal cancer (LARC). This study aimed to evaluate the value of a radiomics model based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the preoperative assessment of LRP-1 and survivin expressions in these patients.MethodsOne hundred patients with pathologically confirmed LARC who underwent DCE-MRI before surgery between February 2017 and September 2021 were included in this retrospective study. DCE-MRI perfusion histogram parameters were calculated for the entire lesion using post-processing software (Omni Kinetics, G.E. Healthcare, China), with three quantitative parameter maps. LRP-1 and survivin expressions were assessed by immunohistochemical methods and patients were classified into low- and high-expression groups.ResultsFour radiomics features were selected to construct the LRP-1 discrimination model. The LRP-1 predictive model achieved excellent diagnostic performance, with areas under the receiver operating curve (AUCs) of 0.853 and 0.747 in the training and validation cohorts, respectively. The other four radiomics characteristics were screened to construct the survivin predictive model, with AUCs of 0.780 and 0.800 in the training and validation cohorts, respectively. Decision curve analysis confirmed the clinical usefulness of the radiomics models.ConclusionDCE-MRI radiomics models are particularly useful for evaluating LRP-1 and survivin expressions in patients with LARC. Our model has significant potential for the preoperative identification of patients with radiotherapy resistance and can serve as an essential reference for treatment planning.

PurposeTo compare the ocular surface and meibum microbial communities of humans with Demodex Blepharitis (DB) and healthy controls.MethodsConjunctival sac and meibum samples from 25 DB patients and 11 healthy controls were analyzed using metagenomic next-generation sequencing (mNGS).ResultsThe alpha-diversity of the conjunctival sac microbiome of the DB group (observed, Chao1, ACE) was lower than that of the control group, whereas all meibum diversity indicators were similar. In conjunctival samples, the relative abundance (RA) of the phylum Proteobacteria was significantly higher (p=0.023), and the RA of both phyla Actinobacteria and Firmicutes was significantly lower (p=0.002, 0.025, respectively) in the DB group than that in the control group. In meibum samples, the RA of the phyla Proteobacteria and Actinobacteria were similar, whereas that of the phylum Firmicutes was significantly lower in the DB group (p=0.019) than that in the control group. Linear discriminant analysis with effect size measurement of the conjunctival and meibum microbiomes showed that Sphingobium sp. YG1 and Acinetobacter guillouiae were enriched in the DB group. Sphingobium sp. YG1, Acinetobacter guillouiae and Pseudomonas putida in the DB group were related to more severe ocular surface clinical parameters. Discriminative genera’s principal coordinate analysis separated all control and DB microbiomes into two distinct clusters.ConclusionsProteobacteria’s increased prevalence may indicate ocular microbial community instability. The species Sphingobium sp. YG1 and Acinetobacter guillouiae are potentially pathogenic bacterial biomarkers in DB. Demodex infection mainly affects the ocular surface microbiome rather than penetrating deeper into the meibomian gland.

Increasing attention to skin regeneration has rapidly broadened research on the topic. However, no bibliometric analysis of the field’s research trends has yet been conducted. In response to this research gap, this study analyzed the publication patterns and progress of skin regeneration research worldwide using a bibliometric analysis of 1,471 papers comprising 1,227 (83.4%) original articles and 244 (16.6%) reviews sourced from a Web of Science search. Publication distribution was analyzed by country/region, institution, journal, and author. The frequency of keywords was assessed to prepare a bibliometric map of the development trends in skin regeneration research. China and the United States were the most productive countries in the field: China had the greatest number of publications at 433 (29.4%) and the United States had the highest H-index ranking (59 with 15,373 citations or 31.9%). Author keywords were classified into four clusters: stem cell, biomaterial, tissue engineering, and wound dressing. “Stem cells,” “chitosan,” “tissue engineering,” and “wound dressings” were the most frequent keywords in each cluster; therefore, they reflected the field’s current focus areas. “Immunomodulation,” “aloe vera,” “extracellular vesicles,” “injectable hydrogel,” and “three-dimensional (3D) bioprinting” were relatively new keywords, indicating that biomaterials for skin regeneration and 3D bioprinting are promising research hotspots in the field. Moreover, clinical studies on new dressings and techniques to accelerate skin regeneration deserve more attention. By uncovering current and future research hotspots, this analysis offers insights that may be useful for both new and experienced scholars striving to expand research and innovation in the field of skin regeneration.

Purpose: To evaluate ocular surface manifestations and morphological changes in meibomian glands (MGs) based on artificial intelligence (AI) analysis in patients with Demodex blepharitis.Methods: In this retrospective study, 115 subjects were enrolled, including 64 subjects with Demodex blepharitis and 51 subjects without Demodex blepharitis as control group. Morphological indexes were evaluated for height, width, tortuosity, MG density, total variation, and the three types of corrected total variation as Uneven indexes.Results: There were no statistically significant differences in all MGs’ average tortuosity and width between the two groups. The average height of all MGs and MG density were significantly lower in the Demodex blepharitis group than control group. The total variation and two types of Uneven indexes were significantly higher in the Demodex blepharitis group than in the control group. Especially the Uneven Index of total variation/MG density had an AUC of 0.822. And the sensitivity and specificity were 59.4% and 92.2%, respectively, at a cut-off value of 3971.667. In addition, Demodex blepharitis was associated with significantly lower meibum quality and expressibility, severe atrophy of MGs, a higher ocular surface disease index (OSDI), and more instability of the tear film.Conclusion:Demodex mites are strongly associated with morphological changes in the MGs and may cause uneven gland atrophy. Therefore, the novel characteristic parameter, the Uneven index, may serve as a digital biomarker to evaluate uneven atrophy of MGs and prompt Demodex blepharitis.

Pseudogenes have been considered as non-functional genes. However, peptides and long non-coding RNAs produced by pseudogenes are expressed in different tumors. Moreover, the dysregulation of pseudogenes is associated with cancer, and their expressions are higher in tumors compared to normal tissues. Recent studies show that pseudogenes can influence the liquid phase condensates formation. Liquid phase separation involves regulating different epigenetic stages, including transcription, chromatin organization, 3D DNA structure, splicing, and post-transcription modifications like m6A. Several membrane-less organelles, formed through the liquid phase separate, are also involved in the epigenetic regulation, and their defects are associated with cancer development. However, the association between pseudogenes and liquid phase separation remains unrevealed. The current study sought to investigate the relationship between pseudogenes and liquid phase separation in cancer development, as well as their therapeutic implications.

The WUSCHEL-related homeobox (WOX) proteins are widely distributed in plants and play important regulatory roles in growth and development processes such as embryonic development and organ development. Here, series of bioinformatics methods were utilized to unravel the structural basis and genetic hierarchy of WOX genes, followed by regulation of the WOX genes in four Euphorbiaceae species. A genome-wide survey identified 59 WOX genes in Hevea brasiliensis (H. brasiliensis: 20 genes), Jatropha curcas (J. curcas: 10 genes), Manihot esculenta (M. esculenta: 18 genes), and Ricinus communis (R. communis: 11 genes). The phylogenetic analysis revealed that these WOX members could be clustered into three close proximal clades, such as namely ancient, intermediate and modern/WUS clades. In addition, gene structures and conserved motif analyses further validated that the WOX genes were conserved within each phylogenetic clade. These results suggested the relationships among WOX members in the four Euphorbiaceae species. We found that WOX genes in H. brasiliensis and M. esculenta exhibit close genetic relationship with J. curcas and R. communis. Additionally, the presence of various cis-acting regulatory elements in the promoter of J. curcas WOX genes (JcWOXs) reflected distinct functions. These speculations were further validated with the differential expression profiles of various JcWOXs in seeds, reflecting the importance of two JcWOX genes (JcWOX6 and JcWOX13) during plant growth and development. Our quantitative real-time PCR (qRT-PCR) analysis demonstrated that the JcWOX11 gene plays an indispensable role in regulating plant callus. Taken together, the present study reports the comprehensive characteristics and relationships of WOX genes in four Euphorbiaceae species, providing new insights into their characterization.