OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To investigate treatment strategies for chronic periapical periodontitis in prematurely erupted premolars and provide guidance for managing pulp and periapical diseases in young permanent teeth with immature roots. Methods: A regenerative endodontic procedure (REP) was performed on a prematurely erupted maxillary left first premolar (tooth 24) at Nolla stage Ⅶ with chronic apical periodontitis, following standardized protocols including root canal irrigation, disinfection, and coronal sealing. The case was followed up, and a literature review was conducted. Results: Clinical resolution of symptoms was observed on tooth 24, with sustained root development. After a 20-month follow-up, the tooth had restored biological function. Literature synthesis revealed that periapical infections in prematurely erupted permanent teeth predominently arise from pulp exposure and bacterial infection, with retrograde infection being rare. For young permanent teeth with necrotic pulp, regenerative endodontic procedures has been established as the treatment of choice to promote apical closure and root maturation. The critical steps of regenerative endodontic procedures include thorough disinfection, induced bleeding to form a fibrin scaffold, and coronal sealing to facilitate stem cell recruitment and differentiation. Conclusion Regenerative endodontic procedures represents an effective and viable treatment option for prematurely erupted young permanent teeth with chronic periapical periodontitis.

In order to clarify the effects of drought stress training on the quality and drought resistance of Codonopsis pilosula, this study used PEG to simulate drought stress and employed potting with water control for the drought stress training of C. pilosula plants. The polysaccharide content, secondary metabolites, antioxidant system, and photosynthetic pigment system of C. pilosula after drought stress training were analyzed. The results showed that the content of fructans in the root of C. pilosula increased after two rounds of drought stress treatment, and it was significantly higher than that of the control group. The accumulation of fructans in the root of C. pilosula showed an upward trend during the rehydration treatment. The content of lobetyolin and tangshenoside Ⅰ increased after drought stress treatment compared with that of the control group. The rehydration treatment caused first increasing and then decreasing in the content of lobetyolin, while it had no significant effect on the tangshenoside Ⅰcontent. The content of photosynthetic pigments decreased after drought stress treatment, and it gradually increased during the first round of rehydration and the second round of rehydration. Moreover, the increase was faster in the second round of rehydration than in the first round of rehydration. The content of the peroxidation product malondialdehyde(MDA) and the activities of superoxide dismutase(SOD), peroxidase(POD), and catalase(CAT) increased after drought stress treatment compared with those of the control group, and they showed a tendency of decreasing during rehydration. Moreover, the decrease was faster in the second round of rehydration than in the first round of rehydration. When the plants of C. pilosula after drought stress training were again subjected to severe drought stress, the wilting rate decreased significantly, and the biomass increases significantly. This study showed that the drought stress training could promote the accumulation of polysaccharides and secondary metabolites in the root of C. pilosula. When encountering drought stress again, C. pilosula plants could quickly regulate the antioxidant system and delay the decomposition of chlorophyll to respond to drought stress. The findings provide a theoretical basis for the ecological cultivation of C. pilosula in arid and semi-arid areas.
Codonopsis/growth & development* ; Droughts ; Polysaccharides/metabolism* ; Stress, Physiological ; Water/metabolism* ; Antioxidants/metabolism* ; Photosynthesis ; Drought Resistance

In hypoxic-ischemic brain damage (HIBD), the programmed cell death known as ferroptosis is significantly activated. Microglial cells demonstrate a high level of sensitivity to iron accumulation. Understanding how to regulate the dual role of microglia and transforming the microglial ferroptosis to a moderate and controllable process has considerable implications for the targeted treatment in HIBD. This paper serves as an overview of microglia-mediated ferroptosis in HIBD as a disease model. We discuss various aspects centered around microglia, including pathophysiological mechanisms, polarization and functions of microglia, molecular mechanisms of ferroptosis, signaling pathways, and therapeutic strategies. The review aims to provide a reference for studies of ferroptosis in microglia.
Microglia/physiology* ; Ferroptosis/physiology* ; Humans ; Animals ; Hypoxia-Ischemia, Brain/pathology* ; Signal Transduction

Delirium is a common cause and complication of hospitalization in the elderly and is associated with higher risk of future dementia and progression of existing dementia, of which 70% is Alzheimer's disease (AD). AD and delirium, which are known to be aggravated by one another, represent significant societal challenges, especially in light of the absence of effective treatments. The intricate biological mechanisms have led to numerous clinical trial setbacks and likely contribute to the limited efficacy of existing therapeutics. Artificial intelligence (AI) presents a promising avenue for overcoming these hurdles by deploying algorithms to uncover hidden patterns across diverse data types. This review explores the pivotal role of AI in revolutionizing drug discovery for AD and delirium from target identification to the development of small molecule and protein-based therapies. Recent advances in deep learning, particularly in accurate protein structure prediction, are facilitating novel approaches to drug design and expediting the discovery pipeline for biological and small molecule therapeutics. This review concludes with an appraisal of current achievements and limitations, and touches on prospects for the use of AI in advancing drug discovery in AD and delirium, emphasizing its transformative potential in addressing these two and possibly other neurodegenerative conditions.

In recent years,the market share of food and medicine homology substances has continued to grow,and various types of contamination issues have become the focus of attention both inside and outside the industry.The contamination not only affects the original medicinal quality,but also leads to the accumulation of toxic substances in the human body,causing acute and chronic severe hazards such as vomiting,poisoning and cancer.Therefore,the development of biosensors that can conveniently,accurately and sensitively detect various pollutants in food and medicine homology substances has become a research hotspot.Aptasensors based on metal-organic frameworks(MOFs)with advantages such as strong specificity,rapid response and simple operation,have been widely used in detection of various pollutants.This review focused on the research progress of aptasensors based on MOFs for detection of food and medicine homology contamination in the past few years,and provided a detailed comparison and analysis for detection of chemical pollutants(such as pesticide residues,heavy metal residues,mycotoxins,etc.)and microbial contamination in food and medicine homology substances.Besides,the development trend and possible challenges of MOFs aptasensors in detection of food and medicine homology substances in the future were discussed,which was anticipated to provide a reference for the development of new MOFs aptasensors.

[Objective]To observe the expression of spinal G protein-gated inwardly-rectifying potassium(GIRK)channel subunits 1 and 2 in spinal dorsal horn of morphine-tolerant rats and investigate the regulatory mechanism.[Methods]Twenty four rats were equally and randomly divided into 4 groups:saline,morphine,morphine+saline and morphine+εV1-2.The morphine-tolerant rat model was established by intrathecal administration of morphine(15 μg/d)for 7 days.Thirty minutes before daily morphine administration,rats received protein kinase C-ε(PKCε)selective inhibitor εV1-2 to test its effect on morphine tolerance and GIRK1-2 expression.All rats received behavioral tests on days 1,3,5 and 7 and thereafter immunofluorescence.[Results]Double fluorescence staining showed that GIRK1 and GIRK2 were expressed primarily in the spinal laminae I-Ⅱ and co-immunostained with μ-opioid receptor(MOR).Seven-day intrathecal administration of morphine induced antinociceptive tolerance and a significant reduction of the spinal GIRK1(22.45±10.58 vs.62.83±20.80,P<0.001)and GIRK2(23.67±8.78 vs.50.17±11.05,P=0.001)fluorescence intensity,as compared with saline control rats.In addition,pretreatment with εV1-2 significantly delayed the reduction of morphine antinociception(P<0.001)and prevented the decrease of GIRK1(54.50±10.37 vs.19.33±9.48,P<0.001)and GIRK2(39.83±6.24 vs.15.83±9.58,P=0.001)expression induced by morphine treatment.[Conclusions]Morphine tolerance is closely related to down-regulation of GIRK1-2 expression and PKCε plays a crucial regulatory role herein.

ObjectiveTo assess the clinical efficacy and regulation of skin microbiota in children with atopic dermatitis and damp-heat accumulation syndrome treated by Zhaqu Xiaofeng Powder （楂曲消风散， ZXP）. MethodsNinety children were randomized into a treatment group and a control group， each with 45 children. The treatment group received ZXP orally， while the control group received levocetirizine hydrochloride syrup， both for 4 weeks. The atopic dermatitis severity index （SCORAD）score， visual analog scale （VAS）score for itching， children dermatology life quality index （CDLQI）score， and traditional Chinese medicine syndrome score were assessed before and after 2- and 4-week treatment. Simultaneously， adhering to the principles of sample size in microbial sequencing， 25 children were randomly selected from each group （total 50 children）； skin samples were collected before and after treatment， and skin specimen DNA was extracted for 16S rRNA gene amplifier sequencing； the skin microbiota levels were detected， and the distribution of bacteria， diversity of flora， and differences between groups were compared. ResultsThere were five drop-outs in each group， and 40 cases in each group were included in final analysis. After 2- and 4-week treatment， both groups showed a significant reduction in SCORAD scores， VAS scores， and CDLQI scores， and more reductions were shown after 4-week treatment than 2-week treatment （P＜0.01）. The SCORAD score， VAS score， and CDLQI score of the treatment group were significantly lower than those in the control group after 4-week treatment （P＜0.01）. The scores of upset， thirsty， poor appetite， short red urine， and dry stool were reduced in the treatment group （P＜0.05）， while the scores of thirsty， poor appetite， short and red urine decreased after treatment （P＜0.05）. After 4 weeks of treatment， among the differential genera with abundances ＞0.5% in the treatment group， The cumulative relative abundances of Staphylococcus aureus， Streptococcus_mitis， Escherichia coli and Gemella_haemolysans in the treatment group were downregulated after treatment； in the control group， there was a relative cumulative decrease in the abundance of Streptococcus_mitis. The control group had reduced relative abundance of Streptococcus_mitis， Escherichia coli， Staphylococcus aureus and Gemella_haemolysans， after treatment （P＜0.05）. Alpha diversity analysis revealed an increase in both Chaol index and Shannon index after treatment （P＜0.05）， while there was no significant difference in Chaol index and Shannon index in the control group before and after treatment （P＞0.05）. Higher Chaol index and Shannon index were found in the treatment group （P＜0.05）. Beta diversity analysis showed that there were significant differences in the microbial community structure at the lesion site between the treatment group and the control group before treatment. The microbial community structure in the treatment group was similar after treatment， while there was no significant change in the microbial community structure in the control group before and after treatment. There were significant structure differences of key bacteria genus in both groups before and after treatment. ConclusionZXP used in the treatment of pediatric atopic dermatitis （AD）with the syndrome of damp-heat accumulation， has shown efficacy in reducing the severity of skin lesions， alleviating itching， and enhancing the quality of life in children. This modulation aims to decrease the abundance of pathogenic bacteria while promoting the colonization of beneficial bacteria， thereby altering the skin microbiota and contributing to the treatment of pediatric AD.

Developmental dyslexia (DD) is a prevalent learning disorder, and the KIAA0319 gene is a DD-associated gene, potentially affecting reading ability by influencing brain development. This review provides an overview of the impact of KIAA0319 gene on brain development in fish, non-primate mammals, primate mammals, and humans. In studies involving fish, the kiaa0319 gene was found to be expressed in the brain, eyes and ears of zebrafish. In mammalian studies, abnormal Kiaa0319 gene expression affected neuronal migration direction and final position, as well as dendritic morphology during embryonic development in rats, leading to abnormal white and gray matter development. Knocking down the Kiaa0319 gene impaired the primary auditory cortex in rats, resulting in phoneme processing impairment similar to DD. In mice, Kiaa0319 overexpression affected the neuronal migration process, causing delayed radial migration of neurons to the cortical plate. Knockout of the Kiaa0319 gene led to abnormal development of the gray matter in mice, resulting in reduced volume of the medial geniculate nucleus and then impacting auditory processing. In primate studies, research on marmosets found that KIAA0319 gene is expressed in the visual, auditory, and motor pathways, while studies on chimpanzees revealed that KIAA0319 gene abnormalities primarily affected the gray matter volume and microstructure of the posterior superior temporal gyrus, morphology of the superior temporal sulcus and gray matter volume of the inferior frontal gyrus. The impact of KIAA0319 gene on human brain development is mainly concentrated in the left temporal lobe, where abnormal KIAA0319 gene expression caused reduced gray matter in the left inferior temporal gyrus, middle temporal gyrus and fusiform gyrus, as well as reduced white matter volume in the left temporoparietal cortex. Abnormalities in KIAA0319 gene also led to decreased hemispheric asymmetry in the superior temporal sulcus. The above-mentioned brain regions are crucial for language and reading processing. It is analyzed that the abnormalities in the DD-associated KIAA0319 gene affect neuronal migration and morphology during brain development, resulting in abnormal development of subcortical structures (such as the medial geniculate nucleus and lateral geniculate nucleus) and cortical structures (including the left temporal cortex, temporoparietal cortex and fusiform gyrus) which are involved in human visual and auditory processing as well as language processing. Impairment of the medial geniculate nucleus affects the information transmission to the auditory cortex, leading to impaired phoneme processing. Abnormalities in the magnocellular layers within the lateral geniculate nucleus hinder the normal transmission of visual information to the visual cortex, affecting the dorsal visual pathway. The left temporal lobe is closely related to language and reading, and abnormalities in its gray matter and connections with other brain areas can affect the language and word processing. In summary, abnormalities in the KIAA0319 gene can partly explain current research findings on the cognitive and neural mechanisms of DD, providing a genetic basis for theoretical models related to DD (such as general sensorimotor theory and the magnocellular theory). However, the mechanism of developmental dyslexia is complex, and there are mutual influences between different DD-associated genes and between genes and the environment, which require further exploration.

Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Renal Dialysis ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis