Dynamical network-based evaluation for neuromuscular dysfunction in stroke-induced hemiplegia during standing.

BACKGROUND: A given movement requires precise coordination of multiple muscles under the control of center nervous system. However, detailed knowledge about the changing characteristics of neuromuscular control for multi-muscle coordination in post-stroke hemiplegic patients during standing is still lacking. This study aimed to investigate the hemiplegia-linked neuromuscular dysfunction during standing from the perspective of multi-muscle dynamical coordination by utilizing a novel network approach - weighted recurrence network (WRN). METHODS: Ten male hemiplegic patients with first-ever stroke and 10 age-matched healthy male adults were instructed to stand on a platform quietly for 30 s with eyes opened and eyes closed, respectively. The WRN was constructed based on the surface electromyography signals of 16 muscles from trunk, hips, thighs and calves. Relevant topological parameters, including clustering coefficient (C) and average shortest path length (L), were extracted to evaluate the dynamical coordination of multiple muscles. A measure of node centrality in network theory, degree of centrality (DC), was innovatively introduced to assess the contribution of single muscle in the multi-muscle dynamical coordination. The standing-related assessment metric, center of pressure (COP), was provided by the platform directly. RESULTS: Results showed that the post-stroke hemiplegic patients stood with remarkably higher similarity of muscle activation and more coupled intermuscular dynamics, characterized by higher C and lower L than the healthy subjects (p < 0.05). The DC values and rankings of back, hip and calf muscles on the affected side were significantly decreased, whereas those on the unaffected side were significantly increased in hemiplegia group compared with the healthy group (p < 0.05). Without visual feedback, subjects exhibited enhanced muscle coordination and increased muscle involvement (p < 0.05). A decrease in C and an increase in L of WRN were observed with decreased COP areas (p < 0.05). CONCLUSIONS: These findings revealed that stroke-induced hemiplegia could significantly influence the neuromuscular control, which was manifested as more coupled intermuscular dynamics, abnormal deactivation of muscles on affected side and compensation of muscles on unaffected side from the perspective of multi-muscle coordination. Enhanced multi-muscle dynamical coordination was strongly associated with impaired postural control. This study provides a novel analytical tool for evaluation of neuromuscular dysfunction and specification of responsible muscles for impaired postural control in stroke-induced hemiplegic patients, and could be potentially applied in clinical practice.

[Determination of three methylimidazole compounds in cosmetics by high performance liquid chromatography-tandem mass spectrometry].

Methylimidazole compounds are byproducts formed during the caramel-coloring process and are used in various cosmetics. In addition metronidazole is an antibacterial and anti-inflammatory drug commonly used in modern medicine and is used in cosmetics to treat acne in the short-term. The illegal addition of metronidazole during cosmetics production can result in residual 2-methylimidazole (2-MEI), which, along with 4-methylimidazole (4-MEI), is a class 2B carcinogen. Therefore, establishing efficient, accurate, and sensitive analytical techniques for analyzing methylimidazole compounds in cosmetics is an urgent objective. In this study, a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for simultaneously determining 1-methylimidazole (1-MEI), 2-MEI, and 4-MEI in cosmetics was developed. Cosmetics samples were extracted via ultrasonication in acetonitrile and purified using a mixed cation-exchange (MCX) solid-phase extraction (SPE) column, with subsequent drying under a stream of nitrogen and redissolution in acetonitrile. The resulting solution was then filtered through a 0.22 µm organic filter membrane for further testing. The analytes were separated using an XBridge® shield RP18 chromatographic column (150 mm×4.6 mm, 3.5 µm) and isocratically eluted with 20 mmol/L ammonium formate solution (containing 0.1% formic acid)-acetonitrile (98∶2, v/v). The target compounds were ionized by electrospray ionization (ESI) source, analyzed in multi-reaction monitoring (MRM) mode, and quantified using the external standard method, with the peak area of the quantitative ion and the mass concentration of the compound taken as the longitudinal and transverse coordinates, respectively. Matrix-matching working curves were also constructed. 1-MEI exhibited good linear relationships in the range of 5-200 µg/L, with correlation coefficients (r2)≥0.9994, while 2-MEI and 4-MEI showed good linearities in the range of 2-100 µg/L with r2≥0.9984. The three methylimidazole compounds exhibited limits of detection (LODs) and quantification (LOQs) of 10-30 µg/kg and 25-100 µg/kg, respectively. Under three spiked levels (LOQ, 2LOQ, 10LOQ), the recoveries of three methylimidazole compounds were 80.9%-107.9%, with relative standard deviations (RSDs, n=6) of 1.2%-12.8%. The practicability of the method was examined using 48 cosmetic samples; 4-MEI was detected in nine samples at contents of 26-1000 µg/kg, while two samples contained 240 and 267 µg/kg of 2-MEI, respectively. 1-MEI was not detected in any of the 48 samples tested. The developed method is simple, fast, and highly sensitive, and provides methodological support for assessing risks and monitoring the three methylimidazole compounds in cosmetics through screening.

[Comparative study of total hip arthroplasty with and without femoral osteotomy in Crowe â £ developmental dysplasia of the hip].

OBJECTIVE: To compare the clinical effects of total hip arthroplasty(THA) with and without femoral osteotomy in Crowe Ⅳ developmental hip dislocation(DDH). METHODS: The data on 46 patients who underwent THA for unilateral Crowe Ⅳ DDH between 2012 and 2017 were analyzed retrospectively. They were divided into two groups according to the different surgical methods. There were 24 patients in the osteotomy group, 3 males and 21 females, with an average age of (47.3±9.0) years old ranged from 34 to 57 years old;and 22 patients in the non-osteotomy group, 2 males and 20 females, with an average age of (51.6±8.3) years old ranged from 40 to 61 years old. The operative time, bleed loss, postoperative drainage volume, postoperative complications, ROM of hip, Harris hip score, limb length discrepancy(LLD), and radiological data were recorded. The femoral dislocation height and the implantation depth of sleeve were measured. RESULTS: All patients were followed up. The mean follow-up time was (3.8±1.2) years ranged from 2 to 6 years in the osteotomy group and (3.2±0.9) years ranged from 1 to 5 years in the non-osteotomy group. The operative time(136.8±18.9) min, bleed loss (709.8±89.4) ml, postoperative drainage volume(308.8±98.2) ml of osteotomy group were all significantly greater than those of non-osteotomy group(100.7±15.8)min, (516.5±103.3) ml, (245.3±79.3) ml (P<0.05). The Harris score at the latest follow up was significantly increased compared with preoperative score in two groups (P<0.05), but there was no significant difference between two groups (P>0.05). The LLD at last follow up was significantly increased compared with preoperative LLD in two groups, the LLD in non-osteotomy group(0.7±0.2) cm showed signifcant smaller than the two osteotomy group(1.2±0.4) cm. Between osteotomy and non-osteotomy groups, the preoperative range of motion of hip joint [(89.5±19.7) °vs (102.5±16.8) °], the preoperative height of dislocation of femoral head [(4.56±0.61) cm vs (3.10±0.73) cm], the proximal implant depth of S-ROM [(0.93±0.36) cm vs (1.67±0.28) cm] was significantly different (P<0.05). Eleven patients in the osteotomy group still had claudication, and 4 patients in the non-osteotomy group had mild claudication (P<0.05). In non-osteotomy group, 3 patients developed nerve injury (1 patient of sciatic nerve, 2 patients of femoral nerve) and 1 case developed periprosthetic fracture. In osteotomy group, 2 case of dislocation and 2 cases of periprosthetic fractures. CONCLUSION: Whether osteotomy or not can achieve satisfactory results for treating Crowe type Ⅳ DDH and significantly improve LLD. However, osteotomy is more complex and time-consuming, limb length difference is greater, and the incidence of claudication is higher. Furthermore, patients with smaller preoperative hip mobility, higher femoral dislocation, limb lengthening≥4 cm and severely narrow femoral proximal canals are prone to be peformed with subtrochanteric osteotomy.

In Situ Reconstructing NiFe Oxalate Toward Overall Water Splitting.

Surface reconstruction plays an essential role in electrochemical catalysis. The structures, compositions, and functionalities of the real catalytic species and sites generated by reconstruction, however, are yet to be clearly understood, for the metastable or transit state of most reconstructed structures. Herein, a series of NiFe oxalates (NixFe1- xC2O4, x = 1, 0.9, 0.7, 0.6, 0.5, and 0) are synthesized for overall water splitting electrocatalysis. Whilst NixFe1-xC2O4 shows great hydrogen evolution reaction (HER) activity, the in situ reconstructed NixFe1-xOOH exhibits outstanding oxygen evolution reaction (OER) activity. As identified by the in situ Raman spectroscopy and quasi-in situ X-ray absorption spectroscopy (XAS) techniques, reconstructions from NixFe1-xC2O4 into defective NixFe1-xOOH and finally amorphous NixFe1-xOOH active species (R-NixFe1-xOOH) are confirmed upon cyclic voltammetry processes. Specifically, the fully reconstructed R-Ni0.6Fe0.4OOH demonstrates the best OER activity (179 mV to reach 10 mA cm-2), originating from its abundant real active sites and optimal d-band center. Benefiting from the reconstruction, an alkaline electrolyzer composed of a Ni0.6Fe0.4C2O4 cathode and an in situ reconstructed R-Ni0.6Fe0.4OOH anode achieves a superb overall water splitting performance (1.52 V@10 mA cm-2). This work provides an in-depth structure-property relationship understanding on the reconstruction of catalysts and offers a new pathway to designing novel catalyst.

[Production of neohesperidin from hesperetin by an engineered strain of Escherichia coli].

Neohesperidin is a flavonoid glycoside widely used in the food and pharmaceutical industries. The current production of neohesperidin mainly relies on extraction from plants. Microbial fermentation demonstrates a promising prospect as an environmentally friendly, efficient, and economical method. In this study, we designed and constructed the biosynthetic pathway of neohesperidin in an Escherichia coli strain by introducing the glycosyltransferase UGT73B2 from Arabidopsis thaliana, rhamnose synthase VvRHM-NRS from Vitis vinifera, and rhamnose transferase Cm1,2RhaT from Citrus maxima. After optimization of the module and the uridine diphosphate (UDP)-glucose synthetic pathway, the engineered strain produced 4.64 g/L neohesperidin in a 5 L bioreactor, and the molar conversion rate of hesperetin was 45.8%. This has been the highest titer reported to date for the biosynthesis of neohesperidin in microorganisms. This study lays a foundation for the construction and application of strains with high yields of neohesperidin and provides a potential choice for the microbial production of other flavonoid glycosides.

Association between inflammatory biomarkers before pregnancy and risk of perinatal depression: A prospective cohort study of 4483 women in Sweden.

AIM: Perinatal depression (PND) is a global health concern, affecting millions of childbearing women. Emerging data suggest that inflammation may play a role in the development of PND. Peripheral blood inflammatory biomarkers before pregnancy are widely tested in clinical practice at minimum cost, yet their potential role in PND risk remains unknown. METHODS: We conducted a prospective cohort study of 4483 birthing women during 2009-2021 within the LifeGene study with linkage to Swedish registers. Peripheral blood inflammatory biomarkers were profiled at baseline. Cases of PND were identified using validated tools or clinical diagnosis from subsequent pregnancies and postpartum periods. Logistic regression models were employed to assess the associations of each inflammatory biomarker (z scored) with PND. RESULTS: We identified 495 (11.0 %) PND cases with an average age of 29.2 years. Pre-pregnancy platelet-to-lymphocyte ratio (PLR) was positively associated [OR, 95 % CI:1.14(1.01,1.27)], while lymphocyte count was inversely associated [OR, 95 % CI: 0.89(0.80,0.98)] with PND. A dose-response relationship was indicated for both PLR and lymphocytes when analyzed in categories based on tertile distribution. These associations appeared more pronounced for postpartum depression than antepartum depression and were independent of psychiatric comorbidities. CONCLUSION: With implications for future mechanistic research, these findings suggest that blood levels of lymphocytes and PLR before pregnancy are associated with subsequent risk of PND in a dose-response manner.

Association of obesity indicators with cognitive function among US adults aged 60 years and older: Results from NHANES.

BACKGROUND: Midlife obesity is a significant risk factor for Alzheimer's disease, but the effects of obesity on cognitive function, either detrimental or beneficial, are controversial among older individuals. This study aims to assess this associations of body mass index (BMI) or waist circumference (WC) with cognitive function among United States older individuals. METHODS: A cross-sectional research study was conducted utilizing data from the 2011 to 2014 National Health and Nutrition Examination Survey (NHANES). Initially, the study compared differences in cognitive function among the normal weight, overweight, and obese groups. Subsequently, we examined the relationships between BMI or WC and cognitive function using multivariate linear regression. Finally, structural equation models were constructed to assess the relationships among body shape, lifestyle, and cognitive function pathways. RESULTS: The study included 2254 individuals. Obese subjects had lower scores in the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) word list learning tasks (CERAD-WL) (χ2 = 7.804, p = .020) and digit symbol substitution test (χ2 = 8.869, p = .012). The regression analysis showed that WC was negatively connected with the CERAD-WL score after adjusting for confounding factors (ß = -.029, p = .045). Moreover, WC had a mediating effect on the path from lifestyle to cognition (CERAD-WL). However, there was no difference in the CERAD delayed recall score and the animal fluency test between the obese and the other groups. CONCLUSIONS: Obese older adults exhibited impaired cognitive abilities in terms of learning and working memory performance. The impact of lifestyle on cognition was mediated by obesity-related anthropometric indices. Sleep, physical activity, and diet influenced the degree of obesity, which subsequently determined cognitive function. Prioritizing weight management in elderly people is crucial for safeguarding cognitive function.

Adaptive Ant Colony Optimization Algorithm Based on Real-Time Logistics Features for Instant Delivery.

Ant colony optimization (ACO) algorithm is widely used in the instant delivery order scheduling because of its distributed computing capability. However, the order delivery efficiency decreases when different logistics statuses are faced. In order to improve the performance of ACO, an adaptive ACO algorithm based on real-time logistics features (AACO-RTLFs) is proposed. First, features are extracted from the event dimension, spatial dimension, and time dimension of the instant delivery to describe the real-time logistics status. Five key factors are further selected from the above three features to assist in problem modeling and ACO designing. Second, an adaptive instant delivery model is built considering the customer's acceptable delivery time. The acceptable time is calculated by emergency order mark and weather conditions in the event dimension feature. Third, an adaptive ACO algorithm is proposed to obtain the instant delivery order schedules. The parameters of the probability equation in ACO are adjusted according to the extracted key factors. Finally, the Gurobi solver in Python is used to perform numerical experiments on the classical datasets to verify the effectiveness of the instant delivery model. The proposed AACO-RTLF algorithm shows its advantages in instant delivery order scheduling when compared to the other state-of-the-art algorithms.

The Genome-Wide Identification of the Dihydroflavonol 4-Reductase (DFR) Gene Family and Its Expression Analysis in Different Fruit Coloring Stages of Strawberry.

Dihydroflavonol 4-reductase (DFR) significantly influences the modification of flower color. To explore the role of DFR in the synthesis of strawberry anthocyanins, in this study, we downloaded the CDS sequences of the DFR gene family from the Arabidopsis genome database TAIR; the DFR family of forest strawberry was compared; then, a functional domain screen was performed using NCBI; the selected strawberry DFR genes were analyzed; and the expression characteristics of the family members were studied by qRT-PCR. The results showed that there are 57 members of the DFR gene family in strawberry, which are mainly expressed in the cytoplasm and chloroplast; most of them are hydrophilic proteins; and the secondary structure of the protein is mainly composed of α-helices and random coils. The analysis revealed that FvDFR genes mostly contain light, hormone, abiotic stress, and meristem response elements. From the results of the qRT-PCR analysis, the relative expression of each member of the FvDFR gene was significantly different, which was expressed throughout the process of fruit coloring. Most genes had the highest expression levels in the full coloring stage (S4). The expression of FvDFR30, FvDFR54, and FvDFR56 during the S4 period was 8, 2.4, and 2.4 times higher than during the S1 period, indicating that the DFR gene plays a key role in regulating the fruit coloration of strawberry. In the strawberry genome, 57 members of the strawberry DFR gene family were identified. The higher the DFR gene expression, the higher the anthocyanin content, and the DFR gene may be the key gene in anthocyanin synthesis. Collectively, the DFR gene is closely related to fruit coloring, which lays a foundation for further exploring the function of the DFR gene family.

Clinicopathological features and treatment outcome of juvenile idiopathic inflammatory myopathies with anti-melanoma differentiation associated gene 5 antibodies: A case series study.

To characterize the clinicopathological features and treatment outcomes of juvenile idiopathic inflammatory myopathies (JIIM) with anti-melanoma differentiation associated gene 5 (MDA5) antibodies in a Chinese cohort. Anti-MDA5 antibody was detected by immunodot assay and indirect immunofluorescence assay on HEK293 cells in a series of Chinese JIIM cohort between 2005 and 2022. The clinical features, histological findings, and treatment outcomes of these anti-MDA5-antibody-positive patients were summarized. Of 59 JIIM patients, 3 (5.08%) were found to be anti-MDA5-antibody-positive. The frequency of anti-MDA5 antibody did not show significant difference between adult idiopathic inflammatory myopathies and JIIM cohorts (P = .720). The disease duration in patients with anti-MDA5 antibody was 2.83 ±â€…1.04 months. All 3 patients had typical skin lesions including Gottron sign and heliotrope rash, while interstitial lung disease and arthritis was only found in 1 patient. All 3 patients showed normal creatine kinase levels. On muscle biopsy, diffuse major histocompatibility complex class-I expression was seen in 3 patients and myxovirus-resistance protein A expression was found in 2 patients. All patients received long-term follow-up (6.42 ±â€…4.01 years). They were all drug-free and showed favorable treatment outcome with prednisone and additional immunosuppressant. Our study indicates that anti-MDA5 antibodies may not be common in Chinese JIIM. Anti-MDA5-positive JIIMs are characterized by typical skin lesions of dermatomyositis, normal CK levels, and increased major histocompatibility complex class-I expression. JIIMs with anti-MDA5 generally have good response to immunotherapies.

Transcriptomics Reveals the Pathway for Increasing Brassica chinensis L. Yield under Foliar Application of Titanium Oxide Nanoparticles.

In this study, Brassica chinensis L seedlings after 6 weeks of soil cultivation were treated with foliar application of TiO2 NPs (20 mg/L) for different times. Transcriptomics analysis was employed to investigate the impact of TiO2 NPs on the physiology, growth, and yield of B. chinensis L. Results showed that TiO2 NPs' exposure significantly increased the biomass, total phosphorus, and catalase enzyme activity by 23.60, 23.72, and 44.01%, respectively, compared to the untreated ones (not bulk or ion).TiO2 NPs increased the leaf chlorophyll content by 4.9% and photosynthetic rate by 16.62%, which was attributed to the upregulated expression of seven genes (PetH, PetF, PsaF, PsbA, PsbB, PsbD, and Lhcb) associated with electron transport in photosystem I and light-harvesting in leaves. The water balance of B. chinensis was improved correlating with the altered expressions of 19 aquaporin genes (e.g., PIP2;1 and NIP6;1). The expressions of 58 genes related to plant hormone signaling and growth were dysregulated, with notable downregulations in GA20, SnRK2, and PP2C and upregulations of DELLAs, SAM, and ETR. Moreover, the 11 tricarboxylic acid cycle genes and 13 glycolysis genes appear to stimulate pathways involved in promoting the growth and physiology of B. chinensis. This research contributes valuable insights into new strategies for increasing the yield of B. chinensis.

Clinico-sero-pathological profiles and risk prediction model of idiopathic inflammatory myopathy (IIM) patients with different perifascicular changes.

AIMS: To explore the clinico-sero-pathological characteristics and risk prediction model of idiopathic inflammatory myopathy (IIM) patients with different muscular perifascicular (PF) changes. METHODS: IIM patients in our center were enrolled and the clinico-sero-pathological data were retrospectively analyzed. A decision tree model was established through machine learning. RESULTS: There were 231 IIM patients enrolled, including 53 with perifascicular atrophy (PFA), 39 with perifascicular necrosis (PFN), and 26 with isolated perifascicular enhancement of MHC-I/MHC-II (PF-MHCn). Clinically, PFA patients exhibited skin rashes and dermatomyositis-specific antibodies (DM-MSAs, 74.5%) except for anti-Mi2. PFN patients showed the most severe muscle weakness, highest creatine kinase (CK), anti-Mi2 (56.8%), and anti-Jo-1 (24.3%) antibodies. PF-MHCn patients demonstrated negative MSAs (48.0%) and elevated CK. Histopathologically, MAC predominantly deposited on PF capillaries in PFA but on non-necrotic myofiber in PFN (43.4% and 36.8%, p < 0.001). MxA expression was least in PF-MHCn (36.0% vs. 83.0% vs. 63.2%, p < 0.001). The decision tree model could effectively predict different subgroups, especially PFA and PFN. CONCLUSIONS: Three types of PF change of IIMs representing distinct clinico-serological characteristics and pathomechanism. Undiscovered MSAs should be explored especially in PF-MHCn patients. The three pathological features could be accurately predicted through the decision tree model.

Neuromuscular conditions in post-stroke ankle-foot dysfunction reflected by surface electromyography.

BACKGROUND: Rating scales and linear indices of surface electromyography (sEMG) cannot quantify all neuromuscular conditions associated with ankle-foot dysfunction in hemiplegic patients. This study aimed to reveal potential neuromuscular conditions of ankle-foot dysfunction in hemiplegic patients by nonlinear network indices of sEMG. METHODS: Fourteen male patients with hemiplegia and 10 age- and sex-matched healthy male adults were recruited and tested in static standing position. The characteristics of the root mean square (RMS), median frequency (MF), and three nonlinear indices, the clustering coefficient (C), the average shortest path length (L), and the degree centrality (DC), of eight groups of muscles in bilateral calves were observed. RESULTS: Compared to those of the control group, the RMS of the medial gastrocnemius (MG), flexor digitorum longus (FDL), and extensor digitorum longus (EDL) on the affected side were significantly lower (P < 0.05), and the RMS of the tibial anterior (TA) and EDL on the unaffected side were significantly higher (P < 0.05). The MF of the EDL on the affected side was significantly higher than that on the control side (P < 0.05). The C of the unaffected side was significantly higher than that of the control group, whereas the L was lower (P < 0.05). Compared to those of the control group, the DC of the TA, EDL, and soleus (SOL) on the unaffected sides were higher (P < 0.05), and the DC of the MG on the affected sides was lower (P < 0.05). CONCLUSION: The change trends and clinical significance of these three network indices, including C, L, and DC, are not in line with those of the traditional linear indices, the RMS and the MF. The C and L may reflect the degree of synchronous activation of muscles during a certain motor task. The DC might be able to quantitatively assess the degree of muscle involvement and reflect the degree of involvement of a single muscle. Linear and nonlinear indices may reveal more neuromuscular conditions in hemiplegic ankle-foot dysfunction from different aspects. TRIAL REGISTRATION: ChiCTR2100055090.

A Prospective, Single-Arm, Phase 2 Study of Modified Transarterial Chemoembolization Using Low-Dose Chemotherapy with Blank Microspheres Plus Low-Dose Lenvatinib and Microwave Ablation in Patients with Large (≥7 cm) Unresectable Hepatocellular Carcinoma: The TALEM Trial.

Introduction: For patients with large unresectable hepatocellular carcinoma (HCC), the effectiveness of conventional transarterial chemoembolization (cTACE) remains suboptimal. This study investigated the efficacy and safety of modified TACE using low-dose chemotherapy with blank microspheres (BMS-TACE) plus low-dose lenvatinib (LD-LEN) and microwave ablation (MWA) in patients with large unresectable HCC. Methods: In this prospective, single-arm, phase 2 study, patients with unresectable HCC exceeding the up-to-seven criteria, with maximum tumor diameter ≥7 cm, and without macrovascular invasion or extrahepatic metastases, received initial BMS-TACE (lipiodol, low-dose doxorubicin, and lobaplatin up to 30 mg each, and blank microspheres; subsequently modified and repeated in most patients) plus LD-LEN (4-8 mg/day) and MWA. The primary endpoint was downstaging rate (DSR); secondary endpoints were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events. Results: From November 2019 to March 2022, 43 patients were enrolled. Median follow-up was 21.2 months. Median largest tumor diameter was 11.2 cm (interquartile range [IQR], 7-25). Following BMS-TACE and LD-LEN, downstaging occurred in 37 (86.0%) patients, 32 of whom received MWA, and 8 of whom had a complete response (CR) without MWA. ORR was 93.0% (CR in 32 [74.4%] and partial response in 8 [18.6%] patients). The 1-, 2-, and 3-year PFS rates were 57.5%, 25.9%, and 18.1%, respectively (median PFS, 14.7 months [95% CI: 8.1-19.5]). The 1-, 2-, and 3-year OS rates were 85.8%, 67.7%, and 61.6%, respectively (median OS, 36.4 months [95% CI: 26.8-not reached]). After BMS-TACE, a significant decline in CD11b+/CD33+/HLA-DR- myeloid-derived suppressor cells and early elevation in CXCR5+/CD8+ and CXCR5+/CD4+ T cells were observed (both p < 0.05). Conclusion: BMS-TACE plus LD-LEN and MWA resulted in promising efficacy and tolerable toxicity in patients with large unresectable HCC exceeding the up-to-seven criteria with a maximum tumor diameter ≥7 cm and without macrovascular invasion or extrahepatic metastases.

Microfluidic Engineering of Addressable Multicompartmental Microspheres for Multicellular Systems.

With the advantages of high-throughput manufacturing and customizability, on-microsphere construction of in vitro multicellular analytical systems has garnered significant attention. However, achieving a precise, biocompatible cell arrangement and spatial signal analysis in hydrogel microspheres remains challenging. In this work, a microfluidic method is reported for the biocompatible generation of addressable supersegmented multicompartmental microspheres. Additionally, these microspheres are developed as novel label-free multicellular systems. In the microfluidic approach, controllable microfluidics is used to finely tune the internal microstructure of the microspheres, and the gas ejector ensures the biocompatibility of the preparation process. As a proof of concept, six- and twenty-compartment microspheres were obtained without the addition of any biohazardous reagents. For microsphere decoding, the visualization of two basic compartments can provide clues for identifying label-free cells due to the structural regularity of the microspheres. Finally, by encapsulating cells of different types, these microspheres as multicellular systems were successfully used for cell coculture and drug testing. These biocompatible, scalable, and analyzable microspheres will open up new prospects for biomedical analysis.

Individualized gray matter morphological abnormalities uncover two robust transdiagnostic biotypes.

Psychiatric disorders exhibit a shared neuropathology, yet the diverse presentations among patients necessitate the identification of transdiagnostic subtypes to enhance diagnostic and treatment strategies. This study aims to unveil potential transdiagnostic subtypes based on personalized gray matter morphological abnormalities. A total of 496 patients with psychiatric disorders and 255 healthy controls (HCs) from three distinct datasets (one for discovery and two for validation) were enrolled. Individualized gray matter morphological abnormalities were determined using normative modeling to identify transdiagnostic subtypes. In the discovery dataset, two transdiagnostic subtypes with contrasting patterns of structural abnormalities compared to HCs were identified. Reproducibility and generalizability analyses demonstrated that these subtypes could be generalized to new patients and even to new disorders in the validation datasets. These subtypes were characterized by distinct disease epicenters. The gray matter abnormal pattern in subtype 1 was mainly linked to excitatory receptors, whereas subtype 2 showed a predominant association with inhibitory receptors. Furthermore, we observed that the gray matter abnormal pattern in subtype 2 was correlated with transcriptional profiles of inflammation-related genes, while subtype 1 did not show this association. Our findings reveal two robust transdiagnostic biotypes, offering novel insights into psychiatric nosology.

Using a new analytic approach for genotyping and phenotyping chromosome 9p deletion syndrome.

Using a new analytic method ("unique non-overlapping region" (UNOR) analysis), we characterized the genotypes and phenotypes of a large cohort of individuals diagnosed with chromosome 9p deletion syndrome (9PMS) and defined critical genomic regions. We extracted phenotypic information from 48 individuals with 9PMS from medical records and used a guided interview with caregivers to clarify ambiguities. Using high-resolution whole-genome sequencing for breakpoint definition, we aligned deletions and drew virtual breakpoints to obtain UNORs associated with phenotypic characteristics. We next extracted genotype and phenotype data for 57 individuals identified from a systematic review of the 9PMS literature and analyzed these as above. Common phenotypic features included developmental delay/intellectual disability, dysmorphic features, hypotonia, genital defects in XY individuals, psychiatric diagnoses, chronic constipation, atopic disease, vision problems, autism spectrum disorder, gastroesophageal reflux disease, trigonocephaly, congenital heart disease, and neonatal hypoglycemia. Our approach confirmed previous literature reports of an association of FREM1 with trigonocephaly and suggested a possible modifier element for this phenotype. In conclusion, the UNOR approach delineated phenotypic characteristics for 9PMS and confirmed the critical role of FREM1 and a possible long-distance regulatory element in pathogenesis of trigonocephaly that will need to be replicated in future studies.

Two new compounds isolated from the aerial parts of gastrodia elata blume.

Two new aromatic compounds, namely gastupdin A (1), and gastupdin B (2), together with three known compounds, arundin(3), phomosines B (4) and monocillin IV (5), were isolated from the aerial parts of Gastrodia elata Blume. The structures of the new compounds were confirmed through spectral analyses including NMR, HR-ESI-MS, ECD, UV, and IR. All isolated compounds were evaluated for their neuroprotective effects against 6-hydroxydopamine-induced cell death in Human Neuroblastoma Cells, with curcumin as the positive control, however, the activity of all compounds was weaker than the positive control, showing no significant activity.

The use of adjuvant chemotherapy combined with concurrent chemoradiotherapy enhances survival rates in cases of locally advanced nasopharyngeal carcinoma.

This study aimed to evaluate the impact of adjuvant chemotherapy on survival rates, adverse events, and quality of life (QOL) in patients with locally advanced nasopharyngeal carcinoma (NPC). A retrospective cohort study was conducted, including patients with firstly histologically confirmed non-metastatic stage III-IVB NPC between February 2018 and February 2020, and with continuous follow-up data available, were chosen from the medical records of the affiliated hospital of Qingdao University and Zibo Central Hospital. There were 395 patients receiving concurrent chemoradiotherapy (CCRT) with adjuvant chemotherapy (adjuvant chemotherapy group) and 428 patients receiving CCRT alone (control group). The two groups were compared for treatment response, adverse events, and QOL scores. Besides, Kaplan-Meier plots, and multivariate COX analysis were conducted. The adjuvant chemotherapy group demonstrated a significantly higher overall survival and disease-free survival compared to the control group. The use of adjuvant chemotherapy was significantly correlated with improved overall survival and disease-free survival. Adjuvant chemotherapy was associated with reduced local recurrence and distant metastasis rates. However, higher rates of adverse events were observed in the adjuvant chemotherapy group. QOL scores for physical functioning, emotional functioning, and overall quality of life were higher in the adjuvant chemotherapy group. The findings of this study indicate that adjuvant chemotherapy in locally advanced NPC is associated with improved treatment response, extended overall and disease-free survivals, and better QOL, despite higher rates of adverse events.

Antibiotic prophylaxis vs. on­demand antibiotic treatment in endoscopic therapy for variceal hemorrhage: A meta­analysis of randomized controlled trials.

The aim of the present study was to conduct a meta-analysis for elucidating the effects of antibiotic prophylaxis on infection, rebleeding and mortality in patients who underwent endoscopic therapy for variceal hemorrhage. Articles on antibiotic prophylaxis and on-demand antibiotic administration following endoscopic therapy for acute variceal bleeding were searched on PubMed, Embase and Cochrane Library between January 1959 and February 2024, to elucidate whether the use of prophylactic antibiotics was necessary. The quality of randomized controlled trials (RCTs) was assessed using the Cochrane risk-of-bias assessment tool and RevMan software version 5.4.1 was used for meta-analysis of the data. The current meta-analysis included four RCTs and 322 patients with acute variceal bleeding who underwent endoscopic therapy. All included studies were of high quality according to the Cochrane risk-of-bias assessment tool. According to the results of the meta-analysis, the incidence of infection in the prophylactic antibiotic group was significantly lower than that in the on-demand group [odds ratio (OR), 0.31; 95% confidence interval (CI), 0.13-0.74; P=0.009]. The prophylactic antibiotic group also exhibited a lower incidence of rebleeding compared with that of the on-demand group (OR, 0.37; 95% CI, 0.19-0.72; P=0.003). No significant differences were noted in the incidence of mortality between the two groups (OR, 0.92; 95% CI, 0.45-1.92; P=0.83). In conclusion, the data indicated that antibiotic prophylaxis is recommended to be used in patients who have undergone endoscopic therapy for variceal hemorrhage.