ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Aortic dissection is a life-threatening cardiovascular disease with devastating complications and high mortality. It requires rapid and accurate diagnosis and a focus on prognosis. Many laboratory tests are routinely performed in patients with aortic dissection including D-dimer, brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin. D-dimer shows vital performance in the diagnosis of aortic dissection, and brain natriuretic peptide, cardiac troponin I, C-reactive protein, and procalcitonin exhibits important value in risk stratification and prognostic effect in aortic dissection patients. Our review summarized the clinical utility of these laboratory tests in patients with aortic dissection, aiming to provide advanced and comprehensive evidence for clinicians to better understand these laboratory tests and help their clinical practice.

Objective: To analyze the unregistered treatment situation and its influencing factors among pulmonary tuberculosis patients in Quzhou City, Zhejiang Province from 2017 to 2023, so as to provide a basis for promoting the management of tuberculosis patients and optimizing disease prevention and control strategies. Methods: Data of pulmonary tuberculosis patients including demographic information, etiological results, and mortality status were collected through the China Disease Prevention and Control Information System Infectious Disease Reporting and Surveillance System and the Tuberculosis Management Information System. Pulmonary tuberculosis patients not matched in the Tuberculosis Management Information System were defined as unregistered treatment patients, and the unregistered treatment rate was analyzed. Factors affecting unregistered treatment among pulmonary tuberculosis patients were analyzed using a multivariable logistic regression model. Results: A total of 10 779 pulmonary tuberculosis patients were reported in Quzhou City from 2017 to 2023, including 7 700 males (71.44%) and 3 079 females (28.56%). There were 5 484 cases aged <65 years, accounting for 50.88%. Among them, 630 cases were unregistered treatment, with an unregistered treatment rate of 5.84% (95%CI: 5.42%-6.38%). Multivariable logistic regression analysis showed pulmonary tuberculosis patients aged ≥65 years (OR=1.829, 95%CI: 1.512-2.212) had a higher risk of being unregistered treatment than those aged <65 years; patients with non-local household registration (OR=5.710, 95%CI: 4.724-6.901) had a higher risk than local patients; and patients engaged in housework/unemployed (OR=2.001, 95%CI: 1.421-2.818) or other occupations (OR=2.396, 95%CI: 1.789-3.137) had a higher risk than farmers. The mortality of unregistered treatment pulmonary tuberculosis patients was higher than the registered treatment patients (26.67% vs. 5.02%),with a significantly elevated mortality risk (OR=7.147, 95%CI: 5.738-8.902). Conclusions The unregistered treatment rate among pulmonary tuberculosis patients was well controlled in Quzhou City from 2017 to 2023, but the elderly, patients with non-local household registration, and those engaged in housework/unemployed had a higher risk of unregistered treatment. It is recommended to improve medical and social security policies, strengthen health education on tuberculosis prevention, enhance treatment adherence, and reduce mortality risk.

BACKGROUND: Fibrosis of the connective tissue in the vaginal wall predominates in pelvic organ prolapse (POP), which is characterized by excessive fibroblast-to-myofibroblast differentiation and abnormal deposition of the extracellular matrix (ECM). Our study aimed to investigate the effect of ECM stiffness on vaginal fibroblasts and to explore the role of methyltransferase 3 (METTL3) in the development of POP. METHODS: Polyacrylamide hydrogels were applied to create an ECM microenvironment with variable stiffness to evaluate the effects of ECM stiffness on the proliferation, differentiation, and expression of ECM components in vaginal fibroblasts. METTL3 small interfering RNA and an overexpression vector were transfected into vaginal fibroblasts to evaluate the effects of METTL3 silencing and overexpression on matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal modulation of the ECM. Both procedures were detected by 5-ethynyl-2'-deoxyuridine (EdU) staining, Western blotting (WB), quantitative real-time polymerase chain reaction (RT-qPCR), and immunofluorescence (IF). RESULTS: Vaginal fibroblasts from POP patients exhibited increased proliferation ability, increased expression of α-smooth muscle actin (α-SMA), decreased expression of collagen I/III, and significantly decreased expression of tissue inhibitors of matrix metalloproteinases (TIMPs) in the stiff matrix ( P <0.05). Compared with those from non-POP patients, vaginal wall tissues from POP patients demonstrated a significant increase in METTL3 content ( P <0.05). However, silencing METTL3 expression in vaginal fibroblasts with high ECM stiffness resulted in decreased proliferation ability, decreased α-SMA expression, an increased ratio of collagen I/III, and increased TIMP1 and TIMP2 expression. Conversely, METTL3 overexpression significantly promoted the process of increased proliferation ability, increased α-SMA expression, decreased ratio of collagen I/III and decreased TIMP1 and TIMP2 expression in the soft matrix ( P <0.05). CONCLUSIONS Elevated ECM stiffness can promote excessive proliferation, differentiation, and abnormal ECM modulation, and the expression of METTL3 plays an important role in alleviating or aggravating matrix stiffness-induced vaginal fibroblast-to-myofibroblast differentiation and abnormal ECM modulation.
Humans ; Female ; Extracellular Matrix/metabolism* ; Cell Differentiation/genetics* ; Methyltransferases/metabolism* ; Pelvic Organ Prolapse/pathology* ; Fibroblasts/metabolism* ; Myofibroblasts/metabolism* ; Vagina/metabolism* ; Cell Proliferation/physiology* ; Cells, Cultured ; Middle Aged

In recent years, hybrid brain-computer interfaces (BCIs) have gained significant attention due to their demonstrated advantages in increasing the number of targets and enhancing robustness of the systems. However, Existing studies usually construct BCI systems using intense auditory stimulation and strong central visual stimulation, which lead to poor user experience and indicate a need for improving system comfort. Studies have proved that the use of peripheral visual stimulation and lower intensity of auditory stimulation can effectively boost the user's comfort. Therefore, this study used high-frequency peripheral visual stimulation and 40-dB weak auditory stimulation to elicit steady-state visual evoked potential (SSVEP) and auditory steady-state response (ASSR) signals, building a high-comfort hybrid BCI based on weak audio-visual evoked responses. This system coded 40 targets via 20 high-frequency visual stimulation frequencies and two auditory stimulation frequencies, improving the coding efficiency of BCI systems. Results showed that the hybrid system's averaged classification accuracy was (78.00 ± 12.18) %, and the information transfer rate (ITR) could reached 27.47 bits/min. This study offers new ideas for the design of hybrid BCI paradigm based on imperceptible stimulation.
Brain-Computer Interfaces ; Humans ; Evoked Potentials, Visual/physiology* ; Acoustic Stimulation ; Photic Stimulation ; Electroencephalography ; Evoked Potentials, Auditory/physiology* ; Adult

Objective To explore the effect of rotenone exposure on the metabolic homeostasis of nicotinamide adenine dinucleotide(NAD+)in dopaminergic neurons of the rat mid-brain striatum,and investigate the effect of exogenous NAD+intervention on the cellular damage response of dopaminergic neurons induced by rotenone.Methods Male SD rats(8 weeks old,200～250 g)were divided into a control group using a table of random numbers,a rotenone exposure group,an NAD+-intervention group,and an NAD+group.An intoxication model was established in the rotenone exposure group.NAD+(250 mg/kg)was administered simultaneously with rotenone exposure in the NAD+-intervention group.The NAD+group was only given NAD+,while the control group received no intervention.After modeling,open field test was performed to evaluate behavioral changes.After scarification,serum samples and mid-brain striatal tissues were collected.HE staining was used to observe the morphology of dopaminergic neurons in the striatum.The NAD+content in the tissues was detected with NAD+/NADH kit.Western blotting was employed to determine the contents of tyrosine hydroxylase(TH),nicotinamide phosphoribosyltransferase(NAMPT),nicotinamide mononucleotide adenylyltransferase(NMNAT),and solute carrier family 25 member A51(SLC25A51).ELISA was utilized to measure the content of dopamine in the striatal tissues.Immunohistochemical staining was applied to observe the distribution and contents of TH proteins in the striatal tissues of each group.Results Rotenone exposure significantly affected the vital signs and motor abilities of rats,induced disorderly-arranged,atrophy and deformed neurons in the striatal tissue,decreased the content of TH,rate-limiting enzyme for dopamine synthesis,by approximately 29%(P<0.01),the content of dopamine by about 42%,and that of NAD+by almost 50%(P<0.01),while increased the NADH/NAD+ratio(P<0.01).After exposure,the content of NAMPT,an enzyme related to NAD+synthesis,was decreased by 26%(P<0.05),the contents of NMNAT1-3 and SLC25A51,mitochondrial transporters of NAD+by approximately 21%,38%,43%,and 21%,respectively(P<0.01).Exogenous NAD+intervention improved the motor function of exposure rats and the morphology of dopaminergic neurons in the mid-brain striatal tissue,and restored the content of TH in the striatal tissue significantly by 12.8%(P<0.05),and the content of dopamine by 20.9%(P<0.05).Conclusion Rotenone disrupts the NAD+homeostasis in dopaminergic neurons by inhibiting the NAD+synthesis and transport pathways in the mid-brain striatal tissues,while exogenous NAD+intervention can effectively alleviate the dopaminergic neuron damage induced by rotenone exposure.

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L^-1）， Coptidis Rhizoma group（B group， 38.4 g·L^-1）， processed Euodiae Fructus group（C group， 5.88 g·L^-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L^-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC_0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（C_max） of Ber， Pal， Evo， and Rut were the highest and time to peak（t_max） were the lowest in the liver of A group. In plasma， the AUC_0-t and C_max of Evo and Rut were increased in A group compared with C group， t_max of Pea was elevated and its C_max was decreased in A group compared with D group. In the liver， compared with B-D groups， C_max values of 5 representative components except Pae were elevated， AUC_0-t of Pae was decreased and AUC_0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t_1/2） of each representative components in A group was elevated and t_max was decreased， and C_max of each representative ingredient except Pal was decreased， AUC_0-t values of Ber and Pal were increased， whereas the AUC_0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Organoids,recognized as invaluable models in tumor and stem cell research,assume a pivotal role in the meticulous analysis of diverse datasets pertaining to their growth dynamics,drug screening processes and related phenomena.However,the manual scrutiny and conventional statistical methodologies employed in handling organoid data often grapple with challenges such as diminished precision and efficiency,heightened complexity,escalated human resource requirements,and a degree of subjectivity.Acknowledging the remarkable efficacy of artificial intelligence(AI)in the realms of biology and medicine,the incorporation of AI into organoid research stands poised to enhance the objectivity,precision and expediency of analyses.This integration empowers organoids to more effectively fulfill objectives such as disease modeling,drug screening and precision medicine.Notably,significant strides have been made in AI-driven analyses of organoid image data.The amalgamation of deep learning into image analysis facilitates a more meticulous delineation of the microstructural intricacies and nuanced changes within organoids,achieving a level of accuracy akin to that of experts.This not only elevates the precision of organoid morphology and growth recognition,but also contributes to substantial time and cost savings in research endeavors.Furthermore,the infusion of AI technology has yielded breakthroughs in the processing of organoid omics data,resulting in heightened efficiency in data processing and the identification of latent gene expression patterns.This furnishes novel tools for comprehending cellular development and unraveling the intricate mechanisms underlying various diseases.In addition to image data,AI techniques applied to diverse organoid datasets,encompassing electrical signals and spectra,have realized an unbiased classification of organoid types and states,embarking on a comprehensive journey towards characterizing organoids holistically.In the pivotal domain of drug screening for organoids,AI emerges as a stalwart companion,providing robust support for real-time process monitoring and result prediction.Leveraging high-content microscopy images and sophisticated deep learning models,researchers can dynamically monitor organoid responses to drugs,effecting non-invasive detection of drug impacts and amplifying the precision and efficiency of drug screening processes.Despite the significant strides made by AI in organoid research,challenges persist,encompassing hurdles in data acquisition,constraints in sample quality and quantity,and quandaries associated with model interpretability.Overcoming these challenges necessitates dedicated future research efforts aimed at enhancing data consistency,fortifying model interpretability,and exploring methodologies for the seamless fusion of multimodal data.Such endeavors are poised to usher in a more comprehensive and dependable application of AI in organoid research.In summation,the integration of AI technology introduces unparalleled opportunities to organoid research,resulting in noteworthy advancements.Nevertheless,interdisciplinary research and collaborative efforts remain imperative to navigate challenges and propel the more profound integration of AI into organoid research.The future holds promise for AI to assume an even more prominent role in advancing organoid research toward clinical translation and precision medicine.

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.