Longitudinal association between maternal cardiovascular health in pregnancy and child birth outcomes.

The American Heart Association has updated its definition of cardiovascular health (CVH) with a new framework known as Life's Essential 8 (LE8). Although gestational CVH assessment has been recommended, its significance based on LE8 for birth outcomes is unknown. We thus evaluated the status of gestational CVH based on LE8 in 3036 pregnant women of the Shanghai Maternal-Child Pairs Cohort and the population of China Maternal Nutrition and Health Sciences Survey, and also examined the association between gestational CVH and child birth outcomes. We found that only a small proportion (12.84%) had high CVH, while 1.98% had low CVH in this cohort study. In adjusted models, a 10-point increase in the gestational CVH score, indicating a more favorable score, was associated with lower neonatal size such as birth weight (ß: - 37.05 [95% confidence interval: - 52.93, - 21.16]), birth length (- 0.12[- 0.22, - 0.01]), weight-for-height z-score (- 0.07[- 0.12, - 0.03]), body mass index z-score (- 0.09 [- 0.13, - 0.04]), length-for-age Z-score (- 0.03 [- 0.06, - 0.01]), and weight-for-age z-score (- 0.08 [- 0.12, - 0.05]). Also, a 10-point increase in the gestational CVH score was associated with the lower risk of large for gestational age (LGA) (0.82 [0.73, 0.92]) and macrosomia infant (0.75 [0.64, 0.88]). CVH categories showed similar results. That is, better maternal CVH status in pregnancy was associated with lower neonatal size and lower risks for LGA and macrosomia in newborns.

Nationwide law enforcement impact on the pet bird trade in China.

Conservation enforcement is a direct strategy to combat illegal wildlife trade in open markets. Yet, its large-scale effectiveness has not been widely assessed due to the lack of extensive market data. Between August 2016 and June 2017, a national coordinated enforcement campaign led by the leading Chinese authority to combat illegal migratory bird trade coincided with the largest-ever pet bird market survey across China by voluntary birdwatchers before and after the enforcement, which served as a unique natural experiment. Across 73 markets from 22 Chinese provinces, the dataset contains 140,723 birds of 346 species from 48 families and recorded a drastic decline in bird abundance traded after enforcement. Notably, species protected under China's Wildlife Protection Law declined significantly, while commercially bred species increased, although responses to enforcement were spatially heterogeneous. Our model showed that the national protection level was the best predictor for the trend of traded species, even after accounting for confounding factors such as regional baseline enforcement pressure and wild native bird populations. However, the widely traded native songbirds were not offered adequate national protection. Future policies should consider the pet bird trade patterns, target key areas of trade, and develop a more systematic market survey design to monitor trade.

Prospective associations of maternal cardiometabolic health with children cardiometabolic health at ages 3 to 6 years.

OBJECTIVE: Maternal cardiometabolic health (MCMH) may have critical effects on offspring lifetime CMH, whereas evidence on the relationship between MCMH during pregnancy and children CMH (CCMH) at ages 3∼6 years remains unknown. METHOD: The study included 1478 mother-child dyads from the Shanghai Maternal-Child Pairs Cohort study. MCMH was examined at a mean of 27.8 (24-36) weeks' gestation based on 8 metrics of 'Life Essential 8' framework involving pre-pregnancy body mass index, total cholesterol, glucose level, blood pressure, physical activity, sleep, diet quality, and nicotine exposure. CCMH was examined at the age of 3 to 6 based on 5 metrics including body mass index, physical activity, sleep health, diet quality, and nicotine exposure. To validate the robustness of main analysis, 499 children were selected to reevaluate CCMH by six metrics (adding blood pressure) for sensitivity analysis. RESULTS: Among 1478 mother-child dyads, the mean (SD) MCMH during pregnancy and CCMH scores were 67.07 (SD 8.82) and 73.80 (SD 10.75), respectively. After adjusting important confounders, each 10 points increase in (more favorable) MCMH score was significantly associated with a higher CCMH score (ß: 0.85, [95% confidence interval (CI): 0.22, 1.47]). Subgroup analysis showed similar results in girls but not in boys. For cardiometabolic risks factors in children, the risk of overweight/obesity and hypertension in children decreased with increased MCMH score (overweight/obesity, Relative Risks [RRs]: 0.98, 95%CI: [0.96, 0.99]); hypertension, RRs: 0.66, 95%CI: [0.47, 0.92]). Sensitivity analysis showed similar result. CONCLUSIONS: Better MCMH in pregnancy was associated with better CCMH at ages 3∼6 years.

Genomic profiling informs therapies and prognosis for patients with hepatocellular carcinoma in clinical practice.

Hepatocellular carcinoma (HCC) genomic research has discovered actionable genetic changes that might guide treatment decisions and clinical trials. Nonetheless, due to a lack of large-scale multicenter clinical validation, these putative targets have not been converted into patient survival advantages. So, it's crucial to ascertain whether genetic analysis is clinically feasible, useful, and whether it can be advantageous for patients. We sequenced tumour tissue and blood samples (as normal controls) from 111 Chinese HCC patients at Qingdao University Hospital using the 508-gene panel and the 688-gene panel, respectively. Approximately 95% of patients had gene variations related to targeted treatment, with 50% having clinically actionable mutations that offered significant information for targeted therapy. Immune cell infiltration was enhanced in individuals with TP53 mutations but decreased in patients with CTNNB1 and KMT2D mutations. More notably, we discovered that SPEN, EPPK1, and BRCA2 mutations were related to decreased median overall survival, although MUC16 mutations were not. Furthermore, we found mutant MUC16 as an independent protective factor for the prognosis of HCC patients after curative hepatectomy. In conclusion, this study connects genetic abnormalities to clinical practice and potentially identifies individuals with poor prognoses who may benefit from targeted treatment or immunotherapy.

Development and validation of a prediction model for hypoproteinemia after traumatic spinal cord injury: A multicenter retrospective clinical study.

A multicenter retrospective analysis of conventionally collected data. To identify the potential causes of hypoproteinemia after traumatic spinal cord injury (TSCI) and provide a diagnostic model for predicting an individual likelihood of developing hypoproteinemia. Hypoproteinemia is a complication of spinal cord injury (SCI), an independent risk factor for respiratory failure in elderly patients with SCI, and a predictor of outcomes in patients with cervical SCI. Few nomogram-based studies have used clinical indicators to predict the likelihood of hypoproteinemia following TSCI. This multicenter retrospective clinical analysis included patients with TSCI admitted to the First Affiliated Hospital of Guangxi Medical University, Wuzhou GongRen Hospital, and Dahua Yao Autonomous County People Hospital between 2016 and 2020. The data of patients from the First Affiliated Hospital of Guangxi Medical University were used as the training set, and those from the other 2 hospitals were used as the validation set. All patient histories, diagnostic procedures, and imaging findings were recorded. To predict whether patients with TSCI may develop hypoproteinemia, a least absolute shrinkage and selection operator regression analysis was conducted to create a nomogram. The model was validated by analyzing the consequences using decision curve analysis, calibration curves, the C-index, and receiver operating characteristic curves. After excluding patients with missing data, 534 patients were included in this study. Male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, urinary tract infection (UTI), hyponatremia, fever, hypotension, and tracheostomy were identified as independent risk factors of hypoalbuminemia. A simple and easy-to-replicate clinical prediction nomogram was constructed using these factors. The area under the curve was 0.728 in the training set and 0.881 in the validation set. The predictive power of the nomogram was satisfactory. Hypoalbuminemia after TSCI may be predicted using the risk factors of male/female sex, age ≥ 60 years, cervical SCI, pneumonia, pleural effusion, UTI, hyponatremia, fever, hypotension, and tracheostomy.

[Altitude Distribution Characteristics of Farmland Soil Bacteria in Loess Hilly Region of Ningxia].

It is of great significance for the conservation of biodiversity in farmland ecosystems to study the diversity, structure, functions, and biogeographical distribution of soil microbes in farmland and their influencing factors. High-throughput sequencing technology was used to analyze the distribution characteristics of soil bacterial diversity, community structure, and metabolic function along elevation and their responses to soil physicochemical properties in farmland in the loess hilly areas of Ningxia. The results showed that:① The Alpha diversity index of soil bacterial was significantly negatively correlated with elevation (P < 0.05) and showed a trend of decreasing and then slightly increasing along the elevation. ② Seven phyla, including Proteobacteria, Actinobacteria, and Acidobacteria, were the dominant groups, and five of them showed highly significant differences between altitudes (P < 0.01). ③ At the secondary classification level, there were 36 metabolic functions of bacteria, including membrane transport, carbohydrate metabolism, and amino acid metabolism, of which 22 showed significant differences, and 12 showed extremely significant differences among different altitudes. ④ Pearson correlation analysis showed that soil water content, bulk density, pH, and carbon-nitrogen ratio had the most significant effects on bacterial Alpha diversity, whereas soil nutrients such as total organic carbon, total nitrogen, and total phosphorus had significant effects on bacterial Beta diversity. ⑤ Mantel test analysis showed that the soil water content, total organic carbon, and carbon-nitrogen ratio affected bacterial community structure at the phylum level, and soil pH, total organic carbon, total nitrogen, total phosphorus, and carbon-nitrogen ratio were significantly correlated with bacterial metabolic function. Variance partitioning analysis showed that soil water content had the highest explanation for the community structure of soil bacteria, whereas soil pH had the highest explanation for metabolic function. In conclusion, soil water content and pH were the main factors affecting the diversity, community composition, and metabolic function of soil bacteria in farmland in the loess hilly region of Ningxia.

Identification of Drought-Resistant Response in Proso Millet (Panicum miliaceum L.) Root through Physiological and Transcriptomic Analysis.

Proso millet (Panicum miliaceum L.) is resilient to abiotic stress, especially to drought. However, the mechanisms by which its roots adapt and tolerate salt stress are obscure. In this study, to clarify the molecular mechanism of proso millet in response to drought stress, the physiological indexes and transcriptome in the root of seedlings of the proso millet cultivar 'Yumi 2' were analyzed at 0, 0.5, 1.0, 1.5, and 3.0 h of stimulated drought stress by using 20% PEG-6000 and after 24 h of rehydration. The results showed that the SOD activity, POD activity, soluble protein content, MDA, and O2-· content of 'Yumi 2' increased with the time of drought stress, but rapidly decreased after rehydration. Here, 130.46 Gb of clean data from 18 samples were obtained, and the Q30 value of each sample exceeded 92%. Compared with 0 h, the number of differentially expressed genes (DEGs) reached the maximum of 16,105 after 3 h of drought, including 9153 upregulated DEGs and 6952 downregulated DEGs. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that upregulated DEGs were mainly involved in ATP binding, nucleus, protein serine/threonine phosphatase activity, MAPK signaling pathway-plant, plant-pathogen interactions, and plant hormone signal transduction under drought stress, while downregulated DEGs were mainly involved in metal ion binding, transmembrane transporter activity, and phenylpropanoid biosynthesis. Additionally, 1441 TFs screened from DEGs were clustered into 64 TF families, such as AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families. Genes related to physiological traits were closely related to starch and sucrose metabolism, phenylpropanoid biosynthesis, glutathione metabolism, and plant hormone signal transduction. In conclusion, the active oxygen metabolism system and the soluble protein of proso millet root could be regulated by the activity of protein serine/threonine phosphatase. AP2/ERF-ERF, bHLH, WRKY, NAC, MYB, and bZIP TF families were found to be closely associated with drought tolerance in proso millet root. This study will provide data to support a subsequent study on the function of the drought tolerance gene in proso millet.

circCDK13-loaded small extracellular vesicles accelerate healing in preclinical diabetic wound models.

Chronic wounds are a major complication in patients with diabetes. Here, we identify a therapeutic circRNA and load it into small extracellular vesicles (sEVs) to treat diabetic wounds in preclinical models. We show that circCDK13 can stimulate the proliferation and migration of human dermal fibroblasts and human epidermal keratinocytes by interacting with insulin-like growth factor 2 mRNA binding protein 3 in an N6-Methyladenosine-dependent manner to enhance CD44 and c-MYC expression. We engineered sEVs that overexpress circCDK13 and show that local subcutaneous injection into male db/db diabetic mouse wounds and wounds of streptozotocin-induced type I male diabetic rats could accelerate wound healing and skin appendage regeneration. Our study demonstrates that the delivery of circCDK13 in sEVs may present an option for diabetic wound treatment.

Prenatal maternal stress, sleep quality, and neonatal birth weight: A prospective cohort study.

To assess if the impacts of prenatal maternal stress (PNMS) on neonatal physical development including birth weight and body length vary by trimesters, and to explore the mediating effect of sleep quality in the relationships. A total of 2778 pregnant women were included from the Shanghai Maternal-Child Pairs Cohort. PNMS and sleep quality were measured in the first trimester (12-16 gestational weeks) and third trimester (32-36 gestational weeks) using the Life Event Scale for Pregnant Women (LESPW) and Pittsburgh Sleep Quality Index, respectively. And total LESPW scores were classified into three groups: high stress (≥75th percentile), medium stress (≥25th and <75th percentile), and low stress (<25th percentile). Multiple linear and logistic regressions were employed to examine the associations between PNMS and birth weight, and bootstrap were utilized to explore the mediating effects of maternal sleep. Higher (adjusted odds ratio, aOR = 1.521; 95% confidence interval (CI), 1.104-2.096) and medium (aOR = 1.421; 95% CI, 1.071-1.885) PNMS and stress from subjective events (aOR = 1.334; 95% CI, 1.076-1.654) in the first trimester were significantly associated with elevated risk for large for gestational age. Maternal severe negative objective events stress (OE3) in the third trimester were negatively associated with birth weight (ß = -0.667; 95% CI, -1.047∼-0.287), and maternal sleep latency during this period acted as a mediator in the association (indirect effect: ß = -0.0144; 95% CI, -0.0427∼-0.0003). Besides, a significant negative correlation between total LESPW score (ß = -0.022; 95% CI, -0.038∼-0.006; per 100 score) and body length in the third trimester was also observed. The impact of PNMS on neonatal birth weight varies by stress types and exposure timing. Prolonged maternal sleep latency in the third trimester correlated with lower birth weight, and mediating the link of OE3 and birth weight, which might indicate a critical period of vulnerability to the effects of PNMS on neonatal physical development.

Haplotype-resolved T2T reference genomes for wild and domesticated accessions shed new insights into the domestication of jujube.

Chinese jujube (Ziziphus jujuba Mill.) is one of the most important deciduous tree fruits in China, with substantial economic and nutritional value. Jujube was domesticated from its wild progenitor, wild jujube (Z. jujuba var. spinosa), and both have high medicinal value. Here we report the 767.81- and 759.24-Mb haplotype-resolved assemblies of a dry-eating 'Junzao' jujube (JZ) and a wild jujube accession (SZ), using a combination of multiple sequencing strategies. Each assembly yielded two complete haplotype-resolved genomes at the telomere-to-telomere (T2T) level, and ~81.60 and 69.07 Mb of structural variations were found between the two haplotypes within JZ and SZ, respectively. Comparative genomic analysis revealed a large inversion on each of chromosomes 3 and 4 between JZ and SZ, and numerous genes were affected by structural variations, some of which were associated with starch and sucrose metabolism. A large-scale population analysis of 672 accessions revealed that wild jujube originated from the lower reaches of the Yellow River and was initially domesticated at local sites. It spread widely and was then independently domesticated at the Shanxi-Shaanxi Gorge of the middle Yellow River. In addition, we identified some new selection signals regions on genomes, which are involved in the tissue development, pollination, and other aspects of jujube tree morphology and fertilization domestication. In conclusion, our study provides high-quality reference genomes of jujube and wild jujube and new insights into the domestication history of jujube.

The Relationship Between Congenital Heart Disease in Newborns and Maternal Prenatal Folic Acid Supplementation, and Analysis of Other High-Risk Factors.

Objective: To analyze the relationship between congenital heart disease (CHD) in newborns and maternal prenatal folic acid supplementation, as well as other high-risk factors. Method: A retrospective analysis was conducted on clinical data of 114 pregnant women diagnosed with congenital heart disease (CHD) in the prenatal stage at our hospital between January 2021 and January 2023. These pregnant women were included in the case group. Additionally, an equal number of pregnant women with normal examination results during the same period were selected as the control group at a 1:1 ratio. Basic information about the families of pregnant women and information about relevant exposure factors during the periconception period were analyzed based on survey forms previously completed by pregnant women during their prenatal check-ups at the hospital. Possible influencing factors were analyzed through multifactor logistic regression. Results: High-risk factors during the perinatal period for new CHD in newborns include maternal age at this pregnancy >35 years (OR=1.907), the presence of adverse pregnancy history (OR=2.213), a family history of CHD (OR=3.049), exposure to secondhand smoke during the perinatal period (OR=2.934), the use of cold medications (OR=1.719), fever (OR=2.034), exposure to noisy environments (OR=1.981), prolonged use of electronic devices (OR=1.827), consumption of pickled foods (OR=1.892). Prenatal folic acid supplementation is a protective factor for new CHD in newborns (OR=0.342). Conclusion: Pregnant women should choose an appropriate gestational age for conception. During the perinatal period, pregnant women should avoid exposure to the aforementioned high-risk factors as much as possible and supplement folic acid appropriately. It is essential to cultivate good dietary and lifestyle habits, as this has significant implications for preventing and reducing the occurrence of CHD in newborns. Healthcare professionals should prioritize educating pregnant women about the risks associated with the identified high-risk factors and emphasize the importance of early prenatal care. Furthermore, promoting appropriate folic acid supplementation during the periconception period should be an integral part of prenatal care protocols. By implementing these recommendations, healthcare providers can contribute to reducing the occurrence of CHD in newborns and improving maternal and infant health outcomes.

Inhibition of Drp1-mediated mitochondrial fission improves contrast-induced acute kidney injury by targeting the mROS-TXNIP-NLRP3 inflammasome axis.

Acute kidney injury (AKI) is a critical complication known for their extremely high mortality rate and lack of effective clinical therapy. Disorders in mitochondrial dynamics possess a pivotal role in the occurrence and progression of contrast-induced nephropathy (CIN) by activating NLRP3 inflammasome. The activation of dynamin-related protein-1 (Drp1) can trigger mitochondrial dynamic disorders by regulating excessive mitochondrial fission. However, the precise role of Drp1 during CIN has not been clarified. In vivo experiments revealed that inhibiting Drp1 through Mdivi-1 (one selective inhibitor of Drp1) can significantly decrease the expression of p-Drp1 (Ser616), mitochondrial p-Drp1 (Ser616), mitochondrial Bax, mitochondrial reactive oxygen species (mROS), NLRP3, caspase-1, ASC, TNF-α, IL-1ß, interleukin (IL)-18, IL-6, creatinine (Cr), malondialdehyde (MDA), blood urea nitrogen (BUN), and KIM-1. Moreover, Mdivi-1 reduced kidney pathological injury and downregulated the interaction between NLRP3 and thioredoxin-interacting protein (TXNIP), which was accompanied by decreased interactions between TRX and TXNIP. This resulted in increasing superoxide dismutase (SOD) and CAT activity, TRX expression, up-regulating mitochondrial membrane potential, and augmenting ATP contents and p-Drp1 (Ser616) levels in the cytoplasm. However, it did not bring impact on the expression of p-Drp1 (Ser637) and TXNIP. Activating Drp-1though Acetaldehyde abrogated the effects of Mdivi-1. In addition, the results of in vitro studies employing siRNA-Drp1 and plasmid-Drp1 intervention in HK-2 cells treated with iohexol were consistent with the in vivo experiments. Our findings revealed inhibiting Drp1 phosphorylation at Ser616 could ameliorate iohexol -induced acute kidney injury though alleviating the activation of the TXNIP-NLRP3 inflammasome pathway.

Effects of accommodation on geometrical parameters of human lens: A systematic review and meta-analysis.

Purpose: To investigate the effects of accommodation on the geometrical parameters of human lens. Methods: Eight databases from inception to November 2023 were used for the literature search: CNKI, CBM, VIP, Wan-Fang, PubMed, Web of Science, EMBASE, and the Cochrane Library. The Methodological Index for Non-randomized Studies was used to assess the risk of bias. The PRISMA were followed and the following outcomes were taken into consideration: lens diameter (LD), lens thickness (LT), anterior curvature radius (ACR), posterior curvature radius (PCR), lens center position (LCP), and total cross-sectional area (TCSA). This systematic review was registered on an international platform for registered systematic reviews and meta-analysis (INPLASY202260085). Results: A total of 19 studies were included. LT increased by 0.04 mm/D (18 studies; 95% confidence interval [CI], 0.03-0.06; I2 = 96.6%; P < 0.001). At the same time, LD, ACR, and PCR decreased by 0.06 mm/D (6 studies; 95%CI, -0.07-0.05; I2 = 50.1%; P < 0.001), 0.53 mm/D (8 studies; 95%CI, -0.64-0.41; I2 = 96.5%; P < 0.001), and 0.14 mm/D (9 studies; 95%CI, -0.19-0.09; I2 = 94.7%; P < 0.001) during accommodation, respectively. Moreover, LCP shifted forward by 0.01 mm/D (3 studies; 95%CI, -0.02-0.00; I2 = 0.0%; P < 0.001), and TCSA by 0.58 mm2/D (2 studies; 95%CI, 0.41-1.57; I2 = 97.0%; P = 0.457) during accommodation. Conclusions: Changes in LT, LD, ACR, PCR and LCP supported Helmholtz's theory. Different apparatuses or measurement methods influenced the measurement of lens geometrical parameters.

Prognostic and Immunotherapeutic Predictive Value of CAD Gene in Hepatocellular Carcinoma: Integrated Bioinformatics and Experimental Analysis.

Hepatocellular carcinoma (HCC) is a common type of cancer that ranks first in cancer-associated death worldwide. Carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) are the key components of the pyrimidine pathway, which promotes cancer development. However, the function of CAD in HCC needs to be clarified. In this study, the clinical and transcriptome data of 424 TCGA-derived HCC cases were analyzed. The results demonstrated that high CAD expression was associated with poor prognosis in HCC patients. The effect of CAD on HCC was then investigated comprehensively using GO annotation analysis, KEGG enrichment analysis, Gene Set Enrichment Analysis (GSEA), and CIBERSORT algorithm. The results showed that CAD expression was correlated with immune checkpoint inhibitors and immune cell infiltration. In addition, low CAD levels in HCC patients predicted increased sensitivity to anti-CTLA4 and PD1, while HCC patients with high CAD expression exhibited high sensitivity to chemotherapeutic and molecular-targeted agents, including gemcitabine, paclitaxel, and sorafenib. Finally, the results from clinical sample suggested that CAD expression increased remarkably in HCC compared with non-cancerous tissues. Loss of function experiments demonstrated that CAD knockdown could significantly inhibit HCC cell growth and migration both in vitro and in vivo. Collectively, the results indicated that CAD is a potential oncogene during HCC metastasis and progression. Therefore, CAD is recommended as a candidate marker and target for HCC prediction and treatment.

Development and validation of a risk nomogram to estimate risk of hyponatremia after spinal cord injury: A retrospective single-center study.

OBJECTIVE: This study aimed to establish a nomogram-based assessment for predicting the risk of hyponatremia after spinal cord injury (SCI). DESIGN: The study is a retrospective single-center study. PARTICIPANTS: SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University. SETTING: The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China. METHODS: We performed a retrospective clinical study to collect SCI patients hospitalized in the First Affiliated Hospital of Guangxi Medical University from 2016 to 2020. Based on their clinical scores, the SCI patients were grouped as either hyponatremic or non-hyponatremic, SCI patients in 2016-2019 were identified as the training set, and patients in 2020 were identified as the test set. A nomogram was generated, the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to validate the model. RESULTS: A total of 895 SCI patients were retrieved. After excluding patients with incomplete data, 883 patients were finally included in this study and used to construct the nomograms. The indicators used in the nomogram included sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, white blood cell (WBC), albumin and serum Ca2+. These indices were determined by the least absolute shrinkage and selection operator (LASSO) regression analysis. The C-index of the model was 0.81, the area under the curve (AUC) of the training set was 0.82(Cl:0.79-0.85), and the validation set was 0.79(Cl:0.73-0.85). CONCLUSIONS: Nomogram has good predictive ability, sex, completeness of SCI, pneumonia, urinary tract infection, fever, constipation, WBC, albumin and serum Ca2+ were predictors of hyponatremia after SCI.

[Construction and stability analysis of finite element model for spinal canal reconstruction with miniplates fixation].

OBJECTIVE: To establish the finite element model of spinal canal reconstruction and internal fixation,analysis influence of spinal canal reconstruction and internal fixation on spinal stability,and verify the effectiveness and reliability of spinal canal reconstruction and internal fixation in spinal canal surgery. METHODS: A 30-year-old male healthy volunteer with a height of 172 cm and weight of 75 kg was selected and his lumbar CT data were collected to establish a finite element model of normal lumbar L3-L5,and the results were compared with in vitro solid results and published finite element analysis results to verify the validity of the model. They were divided into normal group,laminectomy group and spinal canal reconstruction group according to different treatment methods. Under the same boundary fixation and physiological load conditions,six kinds of activities were performed,including forward bending,backward extension,left bending,right bending,left rotation and right rotation,and the changes of range of motion (ROM) of L3-L4,L4-L5 segments and overall maximum ROM of L3-L5 were analyzed under the six conditions. RESULTS: The ROM displacement range of each segment of the constructed L3-L5 finite element model was consistent with the in vitro solid results and previous literature data,which confirms the validity of the model. In L3-L4,ROM of spinal canal reconstruction group was slightly increased than that of normal group during posterior extension(>5% difference),and ROM of other conditions was similar to that of normal group(<5% difference). ROM in laminectomy group was significantly increase than that in normal group and spinal canal reconstruction group under the condition of flexion,extension,left and right rotation. In L4-L5,ROM in spinal canal reconstruction group was similar to that in normal group(<5% difference),while ROM in laminectomy group was significantly higher than that in normal group and spinal canal reconstruction group(>5% difference). In the overall maximum ROM of L3-L5,spinal canal reconstruction group was only slightly higher than normal group under the condition of posterior extension(>5% difference),while laminectomy was significantly higher than normal group and spinal canal reconstruction group under the condition of anterior flexion,posterior extension,left and right rotation(>5% difference). The changes of each segment ROM and overall ROM of L3-L5 showed laminectomy group>spinal canal reconstruction group>normal group. CONCLUSION: Laminectomy could seriously affect biomechanical stability of the spine,but application of spinal canal reconstruction and internal fixation could effectively reduce ROM displacement of the responsible segment of spine and maintain its biomechanical stability.

Effect of Liver Segments and Hepatic Fibrosis Grade on Repeatability, Reliability, and Diagnostic Efficiency of Intravoxel Incoherent Motion.

BACKGROUND: Intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) is considered a potential marker of hepatic fibrosis (HF). OBJECTIVE: To explore the influencing factors of repeatability and reliability in IVIM-DWI parameters of ROI-based liver segments in participants with HF and healthy volunteers (HV) and to assess the diagnostic efficiency of these parameters in HF. METHODS: Participants with early HF (EHF, n=59) or advanced HF (AHF, n=38) and HV (n=48) were recruited. Two examiners measured IVIM data using mono-, bi-exponential and stretched exponential models. The results and influencing factors of repeatability and reliability of IVIM-DWI, and the diagnostic efficiency were analyzed. RESULTS: The repeatability of D* (CV: 26.62-41.47%) and DDC (CV: 18.01-34.40%) was poor, the repeatability of ADC (CV: 4.95-9.76%), D (CV: 7.09-15.52%), f (CV: 9.35-17.15%), and α (CV: 7.48-13.81%) was better; ordered logistic regression showed statistically significant results of IVIM-derived parameters; the reliability showed no obvious trend, and ordered logistic regression showed statistically significant results of IVIMderived parameters, groups, and partial hepatic segments (all p<0.001). IVIM-derived parameters with relatively good repeatability (CV<20%) and reliability (ICC>0.4) were used to establish regression models for differential diagnosis. The AUC of regression models was 0.744-0.783 (EHF vs. AHF), but no statistically significant parameters were found in the HV vs EHF comparison. CONCLUSION: IVIM-derived parameters were the most important factors affecting the repeatability and reliability, while staging of HF and hepatic segments may be the influencing factors of reliability. IVIM-derived parameters showed medium diagnostic efficiency in distinguishing between EHF and AHF.

When will the immune-stimulating antibody conjugates (ISACs) be transferred from bench to bedside?

Immunostimulatory antibody conjugates (ISACs) as a promising new generation of targeted therapeutic antibody-drug conjugates (ADCs), that not only activate innate immunity but also stimulate adaptive immunity, providing a dual therapeutic effect to eliminate tumor cells. However, several ISACs are still in the early stages of clinical development or have already failed. Therefore, it is crucial to design ISACs more effectively to overcome their limitations, including high toxicity, strong immunogenicity, long development time, and poor pharmacokinetics. This review aims to summarize the composition and function of ISACs, incorporating current design considerations and ongoing clinical trials. Additionally, the review delves into the current issues with ISACs and potential solutions, such as adjusting the drug-antibody ratio (DAR) to improve the bioavailability of ISACs. By leveraging the affinity and bioavailability-enhancing properties of bispecific antibodies, the utility between antibodies and immunostimulatory agents can be balanced. Commonly used immunostimulatory agents may induce systemic immune reactions, and BTK (Bruton's tyrosine kinase) inhibitors can regulate immunogenicity. Finally, the concept of grafting ADC's therapeutic principles is simple, but the combination of payload, linker, and targeted functional molecules is not a simple permutation and combination problem. The development of conjugate drugs faces more complex pharmacological and toxicological issues. Standing on the shoulders of ADC, the development and application scenarios of ISAC are endowed with broader space.

Graph theoretical analysis and independent component analysis of diabetic optic neuropathy: A resting-state functional magnetic resonance imaging study.

AIMS: This study aimed to investigate the resting-state functional connectivity and topologic characteristics of brain networks in patients with diabetic optic neuropathy (DON). METHODS: Resting-state functional magnetic resonance imaging scans were performed on 23 patients and 41 healthy control (HC) subjects. We used independent component analysis and graph theoretical analysis to determine the topologic characteristics of the brain and as well as functional network connectivity (FNC) and topologic properties of brain networks. RESULTS: Compared with HCs, patients with DON showed altered global characteristics. At the nodal level, the DON group had fewer nodal degrees in the thalamus and insula, and a greater number in the right rolandic operculum, right postcentral gyrus, and right superior temporal gyrus. In the internetwork comparison, DON patients showed significantly increased FNC between the left frontoparietal network (FPN-L) and ventral attention network (VAN). Additionally, in the intranetwork comparison, connectivity between the left medial superior frontal gyrus (MSFG) of the default network (DMN) and left putamen of auditory network was decreased in the DON group. CONCLUSION: DON patients altered node properties and connectivity in the DMN, auditory network, FPN-L, and VAN. These results provide evidence of the involvement of specific brain networks in the pathophysiology of DON.

Glycogen synthase kinase-3: A potential immunotherapeutic target in tumor microenvironment.

Glycogen synthase kinase-3(GSK-3) is a protein kinase that can phosphorylate over a hundred substrates and regulate cell differentiation, proliferation, and death. Researchers have acknowledged the pivotal role of abnormal activation of GSK-3 in the progression of various diseases over the past few decades. Recent studies have mostly concentrated on investigating the function of GSK-3 in the tumor microenvironment, specifically examining the interaction between TAM, NK cells, B cells, and T cells. Furthermore, GSK-3 exhibits a strong association with immunological checkpoints, such as programmed cell death protein 1. Novel GSK-3 inhibitors have potential in tumor immunotherapy, exerting beneficial effects on hematologic diseases and solid tumors. Nevertheless, there is a lack of reviews about the correlation between tumor-associated immune cells and GSK-3. This study intends to analyze the function and mechanism of GSK-3 comprehensively and systematically in the tumor microenvironment, with a special focus on its influence on various immune cells. The objective is to present novel perspectives for GSK-3 immunotherapy.