This study explores the mechanism of Guben Jiannao Liquid on Alzheimer's disease(AD) by regulating autophagy based on the liver kinase B1(LKB1)/adenosine monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR) pathway. Male SD rats were randomly divided into the blank group, model group, low-dose and high-dose groups of Guben Jiannao Liquid, and rapamycin group, with 10 rats in each group. Except for the blank group, all other groups of rats were injected bilaterally in the hippocampus with β-amyloid(Aβ)_(1-42) to establish the AD model. The low-dose(6.21 g·kg~(-1)) and high-dose(12.42 g·kg~(-1)) groups of Guben Jiannao Liquid and rapamycin group(1 mg·kg~(-1)) were given the corresponding drugs by gavage, and the blank and model groups were given an equal volume of saline by gavage for four weeks. Morris water maze was used to test the learning and memory ability of rats in each group; hematoxylin-eosin(HE) and Nissl staining were used to observe the morphological and quantitative changes of neurons and Nissl bodies in the CA1 region of rat hippocampus; immunohistochemistry was utilized to detect Aβ-positive cell expression in the CA1 region of rat hippocampus; transmission electron microscopy was employed to observe ultrastructural changes in rat hippocampal tissue, and Western blot was used to examine the protein expression levels of LKB1, p-AMPK/AMPK, p-mTOR/mTOR, Beclin1, p62, and LC3-Ⅱ in the hippocampal tissue of the rats. The results showed that compared with those in the blank group, rats in the model group had elevated evasion latency and decreased number of platform transversal and residence time in the platform quadrant. The number of neurons in the hippocampal area was reduced, and the morphology was impaired. The average integral optical density value of Aβ-positive cells was elevated; the expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were decreased, and the expression levels of p-mTOR/mTOR and p62 were increased. Compared with those in the model group, rats in the low-dose and high-dose groups of Guben Jiannao Liquid had shorter evasion latency, higher number of platform transversal, longer residence time in the platform quadrant, increased number of neurons, decreased expression of Aβ-positive cells and average integral optical density values, and increased number of autophagic lysosomes in hippocampal tissue. The expression levels of LKB1, Beclin1, and LC3-Ⅱ were elevated in the hippocampus of rats in the low-dose group of Guben Jiannao Liquid. The expression levels of LKB1, p-AMPK/AMPK, Beclin1, and LC3-Ⅱ were elevated in the hippocampal tissue of rats in the high-dose group of Guben Jiannao Liquid, and the expression levels of p-mTOR/mTOR and p62 were decreased. The findings suggest that Guben Jiannao Liquid can improve cognitive impairment in AD rats, and its mechanism of action may be related to the activation of the LKB1/AMPK/mTOR signaling pathway and the up-regulation of autophagy level.
Animals ; Alzheimer Disease/physiopathology* ; Male ; TOR Serine-Threonine Kinases/genetics* ; Autophagy/drug effects* ; Rats, Sprague-Dawley ; Protein Serine-Threonine Kinases/genetics* ; AMP-Activated Protein Kinases/genetics* ; Rats ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; AMP-Activated Protein Kinase Kinases ; Humans ; Hippocampus/metabolism*

Individuals with congenital absence of the vas deferens (CAVD) may transmit cystic fibrosis (CF)-causing variants of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene to their offspring through assisted reproductive technology (ART). We aimed to delineate the spectrum and estimate the prevalence of CF-causing variants in Chinese individuals with CAVD through a cohort analysis and meta-analysis. CFTR was sequenced in 145 Chinese individuals with CAVD. CFTR variants were classified as CF-causing or non-CF-causing variants regarding clinical significance. A comprehensive genotype analysis was performed in Chinese individuals with CAVD, incorporating previous studies and our study cohort. The prevalence of CF-causing variants was estimated through meta-analysis. In our cohort, 56 different CFTR variants were identified in 108 (74.5%) patients. Twenty variants were categorized as CF-causing and were detected in 28 (19.3%) patients. A comprehensive genotype analysis of 867 patients identified 174 different CFTR variants. Sixty-four were classified as CF-causing variants, 56.3% of which had not been previously reported in Chinese patients with CF. Meta-analysis showed that 14.8% (95% confidence interval [CI]: 11.0%-18.9%) CAVD cases harbored one CF-causing variant, and 68.6% (95% CI: 65.1%-72.0%) CAVD cases carried at least one CFTR variant. Our study underscores the urgent need for extensive CFTR screening, including sequencing of whole exons and flanking regions and detection of large rearrangements and deep intronic CF-causing variants, in Chinese individuals with CAVD before undergoing ART. The established CF-causing variants spectrum may aid in the development of genetic counseling strategies and preimplantation diagnosis to prevent the birth of a child with CF.
Adult ; Humans ; Male ; China ; Cohort Studies ; Cystic Fibrosis/genetics* ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics* ; Genotype ; Male Urogenital Diseases/genetics* ; Mutation ; Vas Deferens/abnormalities* ; East Asian People/genetics*

Geriatric oral health care encounters significant challenges with the increase in the proportion of older individuals. Age-related changes in the dentition, muscles, and joints result in a decline in objective masticatory function, subjective restoration requirements, and acceptability among the elderly population, with individual variations influenced by systemic health. Considering functional requirements, the adaptability of stomatognathic and systemic health conditions, health economics and other factors, the authors believe that it should not be limited to the conventional "one-to-one" strategy for replacing missing teeth in geriatric prosthodontics. There is an urgent need for a precise and adaptable restoration strategy that is more suitable for older individuals. The proposal of a new concept of functional tooth loss updates the minimal restoration standards for elderly patients and establishes the theory of age-friendly functional restoration. Based on the restoration strategy of functional tooth loss, this paper proposes a new concept termed "age-friendly functional restoration of the stomatognathic system", which integrates treatment considerations including endodontics, periodontology, mucosa, muscles, temporomandibular joint, and systemic health. Efforts should be made in four areas as follows. Firstly, the "assessment of accessible function" should be enhanced by considering the interrelationship between stomatognathic and systemic health. Secondly, the "evaluation of appropriate function" is supposed to be optimised in view of subjective needs and objective evaluation of the stomatognathic system. Moreover, the "formulation of treatment plans" needs to be accomplished with the aid of assistive technologies, such as artificial intelligence, to accurately exert appropriate functional restoration. Lastly, the "management and maintenance of health" is likely to be strengthened through follow-ups, propaganda and education, and preventive healthcare, so as to improve quality of life and ultimately achieve healthy ageing among older individuals.
Humans ; Tooth Loss/therapy* ; Aged ; Stomatognathic System ; Oral Health ; Dental Care for Aged ; Dental Restoration, Permanent/methods*

Objective:RS4;11 cell line was used to establish BCL-2 inhibitor-resistant cell lines of B-cell acute lymphoblastic leukemia(B-ALL)and explore the possible mechanisms of drug resistance.Methods:RS4;11 cell line was continuously induced and cultured by low and ascending concentrations of BCL-2 inhibitors navitoclax and venetoclax to construct navitoclax-resistant cell line RS4;11/Nav and venetoclax-resistant cell line RS4;11/Ven.The cell viability was detected by MTT assay,and the cell apoptosis was detected by flow cytometry.Differentially expressed genes(DEGs)between RS4;11 drug-resistant cell lines and parental cell line were detected by transcriptome sequencing technology(RNA-seq),and mRNA expression levels of DEGs between drug-resistant cell lines and parental cell line were detected by real-time PCR(RT-PCR).Western blot was used to detect the expression levels of BCL-2 family anti-apoptotic proteins in drug-resistant cell lines and parental cell line.Results:The drug-resistant cell lines RS4;11/Nav and RS4;11/Ven were successfully established.The resistance index(RI)of RS4;11/Nav to navitoclax and RS4;11/Ven to venetoclax was 328.655±47.377 and 2 894.027±300.311,respectively.The results of cell apoptosis detection showed that compared with the drug-resistant cell lines,RS4;11 parental cell line were significantly inhibited by BCL-2 inhibitors,while the apoptosis rate of drug-resistant cell lines was not affected by the drugs.Western blot assay showed that the expression of anti-apoptotic proteins of BCL-2 family did not increase significantly in drug-resistant cell lines.RNA-seq,RT-PCR and Western blot assays showed that the expression of EP300 in drug-resistant cell lines was significantly higher than that in parental cell line(P＜0.05).Conclusion:Drug-resistant B-ALL cell lines could be successfully established by exposing RS4;11 cell line to the ascending concentration of BCL-2 inhibitors,and the drug resistance mechanism may be related to the overexpression of EP300.

Aim To dynamically characterize neuronal damage in the cortex and hippocampus of mice follow-ing acute cerebral ischemia/reperfusion(I/R).Meth-ods Male C57BL/6J mice weighing 25-28 g under-went middle cerebral artery occlusion using the fila-ment method,followed by 1 hour of reperfusion to es-tablish the acute cerebral I/R injury mouse model.The experiment comprised a sham surgery group,I/R-6 h group,I/R-24 h group,and I/R-72 h group.Longa neurological function score was used to assess the neu-rological function.Triphenyltetrazolium chloride(TTC)staining was conducted to detect cerebral in-farct volume.Hematoxylin and eosin(HE)staining was utilized to observe brain tissue pathological dam-age.Nissl staining was performed to evaluate neuronal damage.Immunofluorescence histochemistry staining was employed to assess the activation of astrocytes and microglia,as well as neuronal loss.Transmission elec-tron microscopy was used to examine mitochondrial damage in hippocampal neurons.Western blot analysis was conducted to detect the expression levels of mito-chondrial fission-fusion-related proteins p-Drp1/Drp1,Mff,Fis1,and OPA1.Results With prolonged cere-bral I/R time,neurological functional impairment,cerebral infarct volume,neuronal damage in the cortex and hippocampus,glial cell activation,neuronal loss,and mitochondrial damage gradually worsened in mice.The expression of mitochondrial fission-related proteins increased gradually,while the expression of mitochon-drial fusion-related proteins decreased gradually.Con-clusions Neuronal pathological damage,such as glial cell activation,neuronal loss,and mitochondrial dam-age,is gradually aggravated with prolonged cerebral I/R time,which may be associated with mitochondrial dynamics imbalance.

Modern Chinese medicine studies have confirmed that the interaction between traditional Chinese medicine(TCM)and intestinal flora is the key to the treatment of diseases with tradi-tional Chinese medicine.This interplay includes such activities as:traditional Chinese medicine can be metabolized by intestinal flora into effective components with different biological activities from its precursors;TCM chemicals improve the composition of gut microbiota,consequently ameliorating its dysfunction as well as associated pathological conditions;and gut microbiota mediate the interactions between the multiple chemicals in TCM.There-fore,it becomes an important way to understand the modern sci-entific connotation of traditional Chinese medicine theory to study the pharmacological mechanism of the efficacy of traditional Chi-nese medicine by targeting Gut microbiota.

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.

AIM To optimize the extraction process for uracil,hypoxanthine,xanthine,uridine,thymine,inosine,guanosine and 2'-deoxyguanosine from Pheretima guillelmi(Michaelsen),and to determine their contents.METHODS With solid-liquid ratio,ultrasonic time and ultrasonic temperature as influencing factors,contents of hypoxanthine and total nucleosides as evaluation indices,the extraction process was optimized by orthogonal test.HPLC was adopted in the content determination of varioud nucleosides,the analysis was performed on a 30℃thermostatic Agilent C18 column(4.6 mm×250 mm,5 μm),with the mobile phase comprising of methanol-water flowing at 1 mL/min in a gradient elution manner,and the detection wavelength was set at 260 nm.RESULTS The optimal conditions were determined to be 1∶250 for solid-liquid ratio,60 min for ultrasonic time,and 60℃for ultrasonic temperature.Eight nucleosides showed good linear relationships within their own ranges(R2＞0.999 0),whose average recoveries were 99.11%-103.27%with the RSDs of 0.85%-2.89%.CONCLUSION This stable and reliable method can be used for the extraction and content determination of nucleosides from P.guillelmi.