ObjectiveBased on functional near-infrared spectroscopy (fNIRS), we investigated the brain activity characteristics of gross motor tasks in children with autism spectrum disorder (ASD) and motor dysfunctions (MDs) to provide a theoretical basis for further understanding the mechanism of MDs in children with ASD and designing targeted intervention programs from a central perspective. MethodsAccording to the inclusion and exclusion criteria, 48 children with ASD accompanied by MDs were recruited into the ASD group and 40 children with typically developing (TD) into the TD group. The fNIRS device was used to collect the information of blood oxygen changes in the cortical motor-related brain regions during single-handed bag throwing and tiptoe walking, and the differences in brain activation and functional connectivity between the two groups of children were analyzed from the perspective of brain activation and functional connectivity. ResultsCompared to the TD group, in the object manipulative motor task (one-handed bag throwing), the ASD group showed significantly reduced activation in both left sensorimotor cortex (SMC) and right secondary visual cortex (V2) (P<0.05), whereas the right pre-motor and supplementary motor cortex (PMC&SMA) had significantly higher activation (P<0.01) and showed bilateral brain region activity; in terms of brain functional integration, there was a significant decrease in the strength of brain functional connectivity (P<0.05) and was mainly associated with dorsolateral prefrontal cortex (DLPFC) and V2. In the body stability motor task (tiptoe walking), the ASD group had significantly higher activation in motor-related brain regions such as the DLPFC, SMC, and PMC&SMA (P<0.05) and showed bilateral brain region activity; in terms of brain functional integration, the ASD group had lower strength of brain functional connectivity (P<0.05) and was mainly associated with PMC&SMA and V2. ConclusionChildren with ASD exhibit abnormal brain functional activity characteristics specific to different gross motor tasks in object manipulative and body stability, reflecting insufficient or excessive compensatory activation of local brain regions and impaired cross-regions integration, which may be a potential reason for the poorer gross motor performance of children with ASD, and meanwhile provides data support for further unraveling the mechanisms underlying the occurrence of MDs in the context of ASD and designing targeted intervention programs from a central perspective.

Tumor drug resistance is an important problem in the failure of chemotherapy and targeted drug therapy, which is a complex process involving chromatin remodeling. SWI/SNF is one of the most studied ATP-dependent chromatin remodeling complexes in tumorigenesis, which plays an important role in the coordination of chromatin structural stability, gene expression, and post-translation modification. However, its mechanism in tumor drug resistance has not been systematically combed. SWI/SNF can be divided into 3 types according to its subunit composition: BAF, PBAF, and ncBAF. These 3 subtypes all contain two mutually exclusive ATPase catalytic subunits (SMARCA2 or SMARCA4), core subunits (SMARCC1 and SMARCD1), and regulatory subunits (ARID1A, PBRM1, and ACTB, etc.), which can control gene expression by regulating chromatin structure. The change of SWI/SNF complex subunits is one of the important factors of tumor drug resistance and progress. SMARCA4 and ARID1A are the most widely studied subunits in tumor drug resistance. Low expression of SMARCA4 can lead to the deletion of the transcription inhibitor of the BCL2L1 gene in mantle cell lymphoma, which will result in transcription up-regulation and significant resistance to the combination therapy of ibrutinib and venetoclax. Low expression of SMARCA4 and high expression of SMARCA2 can activate the FGFR1-pERK1/2 signaling pathway in ovarian high-grade serous carcinoma cells, which induces the overexpression of anti-apoptosis gene BCL2 and results in carboplatin resistance. SMARCA4 deletion can up-regulate epithelial-mesenchymal transition (EMT) by activating YAP1 gene expression in triple-negative breast cancer. It can also reduce the expression of Ca²⁺ channel IP3R3 in ovarian and lung cancer, resulting in the transfer of Ca²⁺ needed to induce apoptosis from endoplasmic reticulum to mitochondria damage. Thus, these two tumors are resistant to cisplatin. It has been found that verteporfin can overcome the drug resistance induced by SMARCA4 deletion. However, this inhibitor has not been applied in clinical practice. Therefore, it is a promising research direction to develop SWI/SNF ATPase targeted drugs with high oral bioavailability to treat patients with tumor resistance induced by low expression or deletion of SMARCA4. ARID1A deletion can activate the expression of ANXA1 protein in HER2+ breast cancer cells or down-regulate the expression of progesterone receptor B protein in endometrial cancer cells. The drug resistance of these two tumor cells to trastuzumab or progesterone is induced by activating AKT pathway. ARID1A deletion in ovarian cancer can increase the expression of MRP2 protein and make it resistant to carboplatin and paclitaxel. ARID1A deletion also can up-regulate the phosphorylation levels of EGFR, ErbB2, and RAF1 oncogene proteins.The ErbB and VEGF pathway are activated and EMT is increased. As a result, lung adenocarcinoma is resistant to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Although great progress has been made in the research on the mechanism of SWI/SNF complex inducing tumor drug resistance, most of the research is still at the protein level. It is necessary to comprehensively and deeply explore the detailed mechanism of drug resistance from gene, transcription, protein, and metabolite levels by using multi-omics techniques, which can provide sufficient theoretical basis for the diagnosis and treatment of poor tumor prognosis caused by mutation or abnormal expression of SWI/SNF subunits in clinical practice.

Objective To investigate the effectiveness and safety of argatroban combined with antiplatelet therapy in patients with acute mild-to-moderate atherosclerotic cerebral infarction within 72 hours after symptom onset. Methods A total of 452 patients with large atherosclerotic cerebral infarction were enrolled and divided into two groups. The combined therapy group (n=286) received argatroban combined with antiplatelet therapy, while the control group (n=166) received antiplatelet therapy alone. The National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, early neurological deterioration (END), and occurrence of bleeding events were compared between the two groups using a Logistic regression model. Results Statistically significant differences were observed in age, smoking history, time from stroke onset to admission, low-density lipoprotein, and estimated glomerular filtration rate (eGFR) levels between the two groups (P < 0.05). No significant differences were found in infarction location, responsible artery, and atherosclerotic subtype between the combined therapy and control groups (P>0.05). Among patients with atheroscleroticcerebral infarction, the proportion of patients with an mRS score of 0 to 2 at 90 days after combined therapy of argatrobanwas 85.3%, and was 74.5% in the control group (P < 0.05). In patients with an NIHSS score ≥3, the proportion of patients with an mRS score of 0 to 2 at 90 days in the combined therapy group was 19.3%, which was significantly lower than 60.8% in the control group (P < 0.05). For anterior circulation responsible artery occlusion, the proportion of patients with an mRS score of 0 to 2 at 90 days in the combined therapy group was 82.1%, and 67.2% in the control group (P < 0.05). Among atherosclerotic subtypes, the proportion of patients with penetrating artery occlusion and an mRS score of 0 to 2 at 90 days was significantly higher in the combined therapy group compared to the control group (P < 0.05). Conclusion Argatroban combined with antiplatelet therapy can improve neurological outcomes in patients with acute mild-to-moderate atherosclerotic ischemic stroke without increasing the risk of bleeding. The combined therapy offers more pronounced benefits in patients with anterior circulation ischemia and penetrating artery occlusion.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective To investigate the risk factors for bronchopulmonary dysplasia(BPD)in twin preterm infants with a gestational age of<34 weeks,and to provide a basis for early identification of BPD in twin preterm infants in clinical practice.Methods A retrospective analysis was performed for the twin preterm infants with a gestational age of<34 weeks who were admitted to 22 hospitals nationwide from January 2018 to December 2020.According to their conditions,they were divided into group A(both twins had BPD),group B(only one twin had BPD),and group C(neither twin had BPD).The risk factors for BPD in twin preterm infants were analyzed.Further analysis was conducted on group B to investigate the postnatal risk factors for BPD within twins.Results A total of 904 pairs of twins with a gestational age of<34 weeks were included in this study.The multivariate logistic regression analysis showed that compared with group C,birth weight discordance of>25%between the twins was an independent risk factor for BPD in one of the twins(OR=3.370,95%CI:1.500-7.568,P<0.05),and high gestational age at birth was a protective factor against BPD(P<0.05).The conditional logistic regression analysis of group B showed that small-for-gestational-age(SGA)birth was an independent risk factor for BPD in individual twins(OR=5.017,95%CI:1.040-24.190,P<0.05).Conclusions The development of BPD in twin preterm infants is associated with gestational age,birth weight discordance between the twins,and SGA birth.

Sarcopenia is a progressive disease characterized by the loss of skeletal muscle mass and function.The risk of developing sarcopenia increases with age, making it a significant clinical concern for the elderly.However, the molecular mechanism underlying this disease remains unclear, and there is a lack of consensus regarding treatment strategies and evaluation of their effectiveness.In recent years, researchers have explored various factors such as nutrition, exercise, and genetics to understand the mechanisms involved.One such regulatory pathway, the PI3K-Akt signaling pathway, has been found to be associated with multiple factors.This review aims to shed light on the regulatory mechanisms of cytokines, hormones, pro-inflammatory factors, and mitochondria within this pathway in the context of sarcopenia.By doing so, it hopes to offer new insights for the treatment of sarcopenia.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

AIM To investigate the consistency of chemical constituents between formula granules and standard decoction of Coptidis Rhizoma.METHODS Eighteen batches of standard decoctions were prepared,after which the extraction rate and contents,transfer rates of magnolflorine,jatrorrhizine,columbamine,epiberberine,coptisine,palmatine,berberin were determined,HPLC characteristic chromatograms were established.RESULTS There were 11 common peaks in the characteristic chromatograms of 18 batches of standard decoctions and 24 batches of formula granules with the similarities of 0.861-1.000,which were clusterd into two categories.The formula granules and standard decoction demonstrated approximated extraction rate and contents,transfer rates of index constituents.CONCLUSION The chemical constituents between formula granules and standard decoction of Coptidis Rhizoma display good consistency,which can provide references for the quality control,process research and clinical application of the former.

Humans ; Stroke, Lacunar ; Mendelian Randomization Analysis ; Leukocytes ; Telomere/genetics* ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide

Child ; Humans ; Infant ; Esophagus ; Electric Power Supplies ; Eating ; Foreign Bodies