Objective To analyze the relationship of the volume of 87 brain regions with postnatal age and neurobehavior in full-term neonates.Methods A total of 75 full-term newborns[gestational age(39.38±1.22)weeks;male/female(51/24);postnatal age(11.11±6.67)days]without abnormalities on brain MRI(three-dimensional T1-weighted imaging,3D T1WI)at our hospital between November 2010 and September 2017 were retrospectively included.Based on the template of 87 brain regions,the neonatal brains were divided into 87 brain regions and their volumes were calculated by using V-shape Bottleneck network(VB-Net)deep learning segmentation technique,Pearson partial correlation and regression analysis were used to explore the relationship of the volume of each brain region with postnatal age and neurobehavioral scores.Results After adjusting for gestational age,birth weight,head circumference,body length and sex,66.7％of the regional brain volumes(58/87 brain regions)significantly increased with the postnatal age(correlation coefficient r:0.2-0.7,P＜0.05).The volumes of gray matter in bilateral lentiform nucleus,left caudate nucleus,right occipital lobe,right inferior temporal lobe,and bilateral anterior temporal lobe strongly correlated with the postnatal age(r＞0.50,P＜0.05).The gray matter volume of the right occipital lobe linearly increased with age(slope:100.67),and was positively correlated with behavioral scores(r=0.324,P＜0.01).Conclusion Most of regional brain volumes increase with the postnatal age during the neonatal period,and the fastest growth occurs in primary sensorimotor-related brain regions,presenting the spatial heterogeneity.Partial brain region grows with the development of behavioral ability.

TCM functional exercises are the important means of TCM to prevent and cure diseases. By adjusting the bones and muscles externally, adjusting the heart and organs internally, promoting blood circulation, improving sleep disorders, enhancing metabolism and immune capacity, the aim of preventing and treating diseases, prolonging life span, and strengthening the body is achieved. TCM exercises have a significant effect on the treatment of various types of fatigue such as chronic fatigue syndrome, Exercise-induced fatigue, post-stroke fatigue, and cancer-related fatigue.

Objective Investigate the expression level and clinical significance of microRNA-223-3p(miR-223-3p)in the serum of pregnant women with preterm premature rupture of membranes(PPROM).Methods A total of 91 pregnant women who underwent cesarean delivery at the Xuzhou Maternal and Child Health Hospital affiliated with Xuzhou Medical University between April and September 2023 were selected for the study.This included 60 cases of PPROM and 31 cases of term normal pregnant women as the research subjects.The study group was divided based on the pathological results of the membranes into:PPROM group without histological chorioamnionitis(HCA)(PPROM group,n = 37),and PPROM group with HCA(PPROM+HCA group,n = 23).Serum samples from pregnant women were collected before hospital treatment,and the expression level of miR-223-3p in the serum was detected by quantitative real-time PCR(qRT-PCR).The levels of inflammatory factors such as IL-1β,IL-6,IL-8,and TNF-α in the serum were measured by enzyme-linked immunosorbent assay(ELISA).Results The expression level of miR-223-3p in the serum of the PPROM+HCA group was significantly higher than that of the PPROM group and the normal group(P＜0.05).The expression levels of IL-1β,IL-6,IL-8,and TNF-α in the serum of the PPROM+HCA group were also significantly higher than those of the PPROM group and the normal group(P＜0.05).There was a positive correlation between the expression level of miR-223-3p in the serum of the PPROM+HCA group and the expression levels of IL-1β,IL-6,IL-8,and TNF-α(r = 0.553,0.505,0438,0.656,P＜0.05).Conclusion The upregulation of miR-223-3p in the serum of pregnant women with PPROM+HCA is associated with the severity of inflammation in PPROM.

TCM believes that spleen deficiency is the root cause of emotional abnormalities in chronic fatigue syndrome (CFS), and clinical treatment often involves the heart, liver and kidney. TCM therapy has a significant efficacy in CFS emotional abnormalities. It is mostly treated with oral administration of TCM, acupuncture, moxibustion and massage therapy. It may play a therapeutic role by improving oxidative stress and immune inflammation, regulating nerve-endocrine, controlling energy metabolism and other ways. It is suggested to establish the syndrome differentiation standard of CFS emotional abnormality in the future, so as to improve the accuracy of syndrome differentiation and treatment; form a perfect treatment guide or expert consensus to guide the standardized application of various internal and external treatment methods; explore objective indicators based on the pathogenesis, and focus on the morphological and functional changes of disease target brain regions with the help of neuroimaging techniques, so as to improve the diagnosis and prognosis evaluation of CFS; based on the guidance of TCM theory, improve the CFS emotional abnormal animal modeling method.

Traditional Chinese Medicine (TCM) external therapy for sleep disorder of chronic fatigue syndrome (CFS) has good anti-fatigue effect and can improve sleep quality of patients. The treatment for sleep disorders of CFS with TCM external treatment mainly adopts acupuncture, moxibustion, massage, TCM bath, transcutaneous acupoint electrical stimulation and auricular point sticking, etc., or alone, or comprehensive application, or combined with oral Chinese materia medica. The appropriate treatment method can be selected according to the patients' condition and compliance, which reflects the unique advantages of TCM syndrome differentiation and treatment and the treatment according to people and time. The existing research still needs to further form a standardized and recognized diagnosis and treatment system, so as to better guide clinical popularization and application.

Objective: To analyze the prevalence and the risk factors of fungal sepsis in 25 neonatal intensive care units (NICU) among preterm infants in China, and to provide a basis for preventive strategies of fungal sepsis. Methods: This was a second-analysis of the data from the "reduction of infection in neonatal intensive care units using the evidence-based practice for improving quality" study. The current status of fungal sepsis of the 24 731 preterm infants with the gestational age of <34⁺⁰ weeks, who were admitted to 25 participating NICU within 7 days of birth between May 2015 and April 2018 were retrospectively analyzed. These preterm infants were divided into the fungal sepsis group and the without fungal sepsis group according to whether they developed fungal sepsis to analyze the incidences and the microbiology of fungal sepsis. Chi-square test was used to compare the incidences of fungal sepsis in preterm infants with different gestational ages and birth weights and in different NICU. Multivariate Logistic regression analysis was used to study the outcomes of preterm infants with fungal sepsis, which were further compared with those of preterm infants without fungal sepsis. The 144 preterm infants in the fungal sepsis group were matched with 288 preterm infants in the non-fungal sepsis group by propensity score-matched method. Univariate and multivariate Logistic regression analysis were used to analyze the risk factors of fungal sepsis. Results: In all, 166 (0.7%) of the 24 731 preterm infants developed fungal sepsis, with the gestational age of (29.7±2.0) weeks and the birth weight of (1 300±293) g. The incidence of fungal sepsis increased with decreasing gestational age and birth weight (both P<0.001). The preterm infants with gestational age of <32 weeks accounted for 87.3% (145/166). The incidence of fungal sepsis was 1.0% (117/11 438) in very preterm infants and 2.0% (28/1 401) in extremely preterm infants, and was 1.3% (103/8 060) in very low birth weight infants and 1.7% (21/1 211) in extremely low birth weight infants, respectively. There was no fungal sepsis in 3 NICU, and the incidences in the other 22 NICU ranged from 0.7% (10/1 397) to 2.9% (21/724), with significant statistical difference (P<0.001). The pathogens were mainly Candida (150/166, 90.4%), including 59 cases of Candida albicans and 91 cases of non-Candida albicans, of which Candida parapsilosis was the most common (41 cases). Fungal sepsis was independently associated with increased risk of moderate to severe bronchopulmonary dysplasia (BPD) (adjusted OR 1.52, 95%CI 1.04-2.22, P=0.030) and severe retinopathy of prematurity (ROP) (adjusted OR 2.55, 95%CI 1.12-5.80, P=0.025). Previous broad spectrum antibiotics exposure (adjusted OR=2.50, 95%CI 1.50-4.17, P<0.001), prolonged use of central line (adjusted OR=1.05, 95%CI 1.03-1.08, P<0.001) and previous total parenteral nutrition (TPN) duration (adjusted OR=1.04, 95%CI 1.02-1.06, P<0.001) were all independently associated with increasing risk of fungal sepsis. Conclusions: Candida albicans and Candida parapsilosis are the main pathogens of fungal sepsis among preterm infants in Chinese NICU. Preterm infants with fungal sepsis are at increased risk of moderate to severe BPD and severe ROP. Previous broad spectrum antibiotics exposure, prolonged use of central line and prolonged duration of TPN will increase the risk of fungal sepsis. Ongoing initiatives are needed to reduce fungal sepsis based on these risk factors.
Infant ; Infant, Newborn ; Humans ; Birth Weight ; Intensive Care Units, Neonatal ; Retrospective Studies ; Tertiary Care Centers ; Infant, Extremely Low Birth Weight ; Gestational Age ; Infant, Extremely Premature ; Sepsis/epidemiology* ; Retinopathy of Prematurity/epidemiology* ; Bronchopulmonary Dysplasia/epidemiology*

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting both upper and lower motor neurons (MNs) with large unmet medical needs. Multiple pathological mechanisms are considered to contribute to the progression of ALS, including neuronal oxidative stress and mitochondrial dysfunction. Honokiol (HNK) has been reported to exert therapeutic effects in several neurologic disease models including ischemia stroke, Alzheimer's disease and Parkinson's disease. Here we found that honokiol also exhibited protective effects in ALS disease models both in vitro and in vivo. Honokiol improved the viability of NSC-34 motor neuron-like cells that expressed the mutant G93A SOD1 proteins (SOD1-G93A cells for short). Mechanistical studies revealed that honokiol alleviated cellular oxidative stress by enhancing glutathione (GSH) synthesis and activating the nuclear factor erythroid 2-related factor 2 (NRF2)-antioxidant response element (ARE) pathway. Also, honokiol improved both mitochondrial function and morphology via fine-tuning mitochondrial dynamics in SOD1-G93A cells. Importantly, honokiol extended the lifespan of the SOD1-G93A transgenic mice and improved the motor function. The improvement of antioxidant capacity and mitochondrial function was further confirmed in the spinal cord and gastrocnemius muscle in mice. Overall, honokiol showed promising preclinical potential as a multiple target drug for ALS treatment.

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8⁺ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

The application of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated proteins (Cas) can be limited due to a lack of compatible protospacer adjacent motif (PAM) sequences in the DNA regions of interest. Recently, SpRY, a variant of Streptococcus pyogenes Cas9 (SpCas9), was reported, which nearly completely fulfils the PAM requirement. Meanwhile, PAMs for SpRY have not been well addressed. In our previous study, we developed the PAM Definition by Observable Sequence Excision (PAM-DOSE) and green fluorescent protein (GFP)‍-reporter systems to study PAMs in human cells. Herein, we endeavored to identify the PAMs of SpRY with these two methods. The results indicated that 5'-NRN-3', 5'-NTA-3', and 5'-NCK-3' could be considered as canonical PAMs. 5'-NCA-3' and 5'-NTK-3' may serve as non-priority PAMs. At the same time, PAM of 5'-NYC-3' is not recommended for human cells. These findings provide further insights into the application of SpRY for human genome editing.
CRISPR-Associated Protein 9/metabolism* ; CRISPR-Cas Systems ; DNA ; Gene Editing/methods* ; Humans ; Streptococcus pyogenes/metabolism*

Objective:To summarize the clinical experience of treating patients with severe acute organic fluorine poisoning using extracorporeal membrane oxygenation (ECMO).Methods:In January 2021, an acute mass organic fluorine gas poisoning incident occurred in Quzhou, Zhejiang Province. The clinical data of 4 severe patients with acute poisoning of organic fluorine treated by ECMO in our hospital were retrospectively analyzed, and the epidemiological characteristics, clinical symptoms, signs, the abnormal laboratory studies/examinations, and treatments of this kind poisoning patients, especially, the treatment pattern, support time, complications, and outcomes of ECMO were collected and analyzed.Results:All the 4 patients were male, with an average age of (52±9) years, and all of them came to the emergency department complaining chest tightness, cough and pharyngeal discomfort 6 h after exposure by inhalation. The patient’s condition progressed rapidly with severe acute respiratory failure and circulatory failure as the prominent manifestations. The mechanical ventilations were performed (13.0±4.8) h after poisoning, and ECMO treatment was performed (15.5±5.3) h after poisoning. Among them, 2 patients were treated using venoarterial (VA) ECMO, and 2 patients using venovenous (VV) ECMO, but 1 patient was converted to VA-ECMO 8 h later. The duration of ECMO support for the patients was (8.8±3.6) d. The duration of mechanical ventilation was (23.0±28.7) d and stay in intensive care unit was (42.0±55.4) d. Among them, one patient was transferred to a specialized rehabilitation hospital after the amputation surgery due to lower limb necrosis after VA-ECMO support, and the remaining 3 patients were discharged after recovery.Conclusions:ECMO support might have the irreplaceable value in the treatment of patients with severe acute organic fluorine poisoning, and should be considered as one of the reserves of regional health care system in dealing with public health emergencies.