Background: Malignant vasovagal syncope (VVS) is characterized by cardiac arrest lasting more than 3 seconds during a syncope episode or head-up tilt test (HUTT). We aim to conduct a risk assessment for potential malignant VVS before the HUTT by using economic, simple and convenient demographic data, in order to prevent adverse outcomes for pediatric VVS.Purpose: To explore the correlation between demographic factors and pediatric malignant VVS, and verify the value of these factors in early risk assessment for malignant VVS before HUTT, so as to optimize test safety and reduce adverse events. Methods: We conducted a retrospective analysis of the clinical data of 3,734 children who were initially diagnosed with VVS due to unexplained syncope and presyncope. Finally, 122 children who met the diagnostic criteria for malignant VVS were included in the malignant VVS group, and 661 children who did not meet the criteria during the same period were matched as the control group. By analyzing demographic data and other factors, we attempted to clarify the association between these factors and malignant VVS. Results: Linear relationship: age and body mass index (BMI) have independent protective effects on malignant VVS. For every 1-year increase in age and every 1 kg/m2 increase in BMI, the risk of malignant VVS decreases by 12% and 9%, respectively. Nonlinear relationship: When the age is <12.9 years old, for every additional year of age, the risk of malignant VVS decreases by 20%. For ages 12.9 years and above, the efficacy is not significant. There is no significant nonlinear relationship between BMI and malignant VVS. Conclusion Age and BMI are independent protective factors for pediatric malignant VVS. Before the age of 12.9 years, the incidence of malignant VVS gradually decreases with the increase in age, and thereafter there is no significant impact.

ObjectiveTo investigate the effect of schisanlactone E in ameliorating neuroinflammation and synaptic injury in APP/PS1 mice and to elucidate whether its mechanism is related to the regulation of helper T cell 17 （Th17）/regulatory T cell （Treg） immune balance. MethodsAPP/PS1 transgenic mice were assigned into model， low- and high-dose （2 mg·kg^-1·d^-1 and 4 mg·kg^-1·d^-1， respectively） schisanlactone E， and donepezil （1 mg·kg^-1·d^-1） groups. C57BL/6J mice were used as the control group. Each group received the corresponding drug by gavage for 30 days. Learning and memory abilities were assessed by the Morris water maze and novel object recognition tests. The percentages of Th17 and Treg cells in the peripheral blood were analyzed by flow cytometry. The mRNA levels of retinoid-related orphan receptor γt （RORγt）， interleukin （IL）-17A， forkhead box protein 3 （FoxP3）， and IL-4 in the hippocampus were determined by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The synaptic ultrastructure in the hippocampus was observed by transmission electron microscopy. The protein levels of synapsin Ⅰ and postsynaptic density protein 95 （PSD95） in the hippocampus were measured by Western blot. Aβ aggregation and microglial activation in the hippocampus were observed by immunofluorescence staining. The mRNA levels of tumor necrosis factor （TNF）-α， IL-6， and IL-1β in the hippocampus were determined by Real-time PCR. ResultsCompared with the control group， the model group showed prolonged escape latency （P<0.05）， decreased time spent in the target quadrant， platform crossings， novel object exploration time， and percentage of novel object contact frequency （P<0.05， P<0.01）， increased Aβ aggregation in the hippocampal tissue （P<0.01）， an increased proportion of Th17 cells （P<0.05）， a decreased proportion of Treg cells （P<0.05）， and an increased Th17/Treg ratio （P<0.01） in the peripheral blood. Furthermore， the hippocampal tissue in the model group exhibited upregulated mRNA levels of RORγt and IL-17A （P<0.05， P<0.01）， downregulated mRNA levels of FoxP3 and IL-4 （P<0.01）， decreased synapses （P<0.05）， decreased PSD density， synaptic interface curvature， and active zone length （P<0.05， P<0.01）， and increased synaptic cleft width （P<0.05）， downregulated protein levels of Synapsin Ⅰ and PSD95 （P<0.01）， increased microglial activation （P<0.01）， and upregulated mRNA levels of TNF-α， IL-6， and IL-1β （P<0.05）. Compared with the model group， the high-dose schisanlactone E group and the donepezil group exhibited shortened escape latency and increased time in the target quadrant and platform crossings （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased novel object exploration time （P<0.05， P<0.01） and percentage of novel object contact frequency （P<0.05， P<0.01）， and reduced hippocampal Aβ aggregation （P<0.05， P<0.01）. The schisanlactone E groups showed a decreased proportion of Th17 cells （P<0.05） and an increased proportion of Treg cells （P<0.05） in the peripheral blood， and all treatment groups showed a decreased Th17/Treg ratio （P<0.05， P<0.01）. The high-dose schisanlactone E group showed a downregulated mRNA level of RORγt in the hippocampal tissue （P<0.05）， and all treatment groups showed a downregulated mRNA level of IL-17A （P<0.05， P<0.01）， and upregulated mRNA levels of FoxP3 and IL-4 （P<0.05， P<0.01）. The schisanlactone E groups and the donepezil group showed increased synapses， active zone length， synaptic interface curvature， and PSD density， decreased synaptic cleft width （P<0.05， P<0.01）， and upregulated protein levels of synapsin Ⅰ and PSD95 （P<0.05， P<0.01）. The high-dose schisanlactone E group and the donepezil group showed decreased microglial activation in the hippocampus （P<0.01）. The schisanlactone E groups and the donepezil group showed downregulated mRNA levels of TNF-α， IL-6， and IL-1β in the hippocampal tissue （P<0.05， P<0.01）. ConclusionSchisanlactone E significantly improves the cognitive function in APP/PS1 mice by regulating the Th17/Treg immune balance， inhibiting neuroinflammation， and ameliorating synaptic injury.

ObjectiveTo observe the effect of aspirin curcumin ester （CA） on the activation and glucose metabolism reprogramming of the mouse microglia （BV2） model of inflammation induced by high glucose/β-amyloid （Aβ）_1-42， and to explore the potential mechanism of CA in reducing neuroinflammatory response in the brain. MethodsThe BV2 activation model was constructed by high glucose combined with Aβ_1-42 oligomers. BV2 cells were treated with Aβ_1-42 oligomers （10 μmol·L^-1） in a high glucose （50 mmol·L^-1） environment and allocated into normal， high glucose， Aβ， and high glucose + Aβ groups. The cell morphology of each group was observed under a bright field. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to assess the mRNA levels of inflammatory factors including tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， and interleukin-1β （IL-1β） as well as glycolysis-related glucose transporter type 1 （GLUT1）， hexokinase 2 （HK2）， phospofructokinase-2/fructose-2，6-bisphosphatase 3 （PFKFB3）， and pyruvate kinase M2 （PKM2）. To reveal the effects of CA on inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42， this study established the BV2 cell model of inflammatory activation by high glucose and Aβ_1-42 oligomer intervention. The cells were allocated into normal， model （50 mmol·L^-1 glucose + 10 μmol·L^-1 Aβ_1-42）， CA （10 μmol·L^-1）， 2DG （0.2 mmol·L^-1）， and DADA （1 mmol·L^-1） groups. Cell counting kit-8 （CCK-8） was used to detect cell survival rate. The cell morphology of each group was observed under a bright field. The expression of inflammatory factors TNF-α， IL-6， and IL-1β and glycolysis-related key enzymes GLUT1， HK2， PFKFB3， and PKM2 at the mRNA level in each group was measured by real-time PCR. The protein levels of GLUT1， HK2， PFKFB3， and PKM2 were determined by Western blot. The glycolysis rate in each group was measured by seahorse. LC-MS was employed to identify the glucose metabolism intermediates. The morphology of mitochondria in cells was observed by electron microscopy. ResultsConstruction of the BV2 cell model： Compared with the normal group， the Aβ group and the high glucose + Aβ group showed more amoeboid-shaped cells and cell aggregation. The high glucose + Aβ group exhibited increased the mRNA levels of TNF-α， IL-1β， and IL-6 （P<0.05， P<0.01）， as well as those of key glycolytic enzymes GLUT1， HK2， PFKFB3， and PKM2 （P<0.01）. The Aβ group also showed significantly increased mRNA levels of PKM2 and PFKFB3 （P<0.01）. Effects of CA on the inflammatory response and glucose metabolism in BV2 cells exposed to high glucose/Aβ_1-42： Compared with the normal group， the model group exhibited amoeboid-shaped cells and cell aggregation， upregulated mRNA levels of TNF-α， IL-1β， IL-6， iNOS， GLUT1， HK2， PFKFB3， and PKM2 （P<0.01） and protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， an increased basal glycolysis rate （P<0.01）， a decreased compensatory glycolysis rate （P<0.01）， increased glycolytic intermediates and reduced TCA cycle intermediates. In addition， the mitochondria in the model group exhibited a decreased number （P<0.05）， impaired crista integrity （P<0.01）， an increased proportion of vacuolization （P<0.01）， and abnormal mitochondrial morphology. Compared with those in the model group， the number of amoeboid-shaped BV2 cells reduced in the CA and 2DG groups， while most BV2 cells in the DADA group became elongated spindle-shaped. All the three treatment groups showed downregulated mRNA levels of TNF-α， IL-1β， IL-6， GLUT1， HK2， PFKFB3， and PKM2 （P<0.05， P<0.01）， downregulated protein levels of GLUT1， HK2， and PFKFB3 （P<0.05， P<0.01）， and slow compensatory glycolysis and basal glycolysis （P<0.05， P<0.01）. Glycolytic intermediates were decreased and TCA cycle intermediates were increased in the CA and 2DG groups. Mitochondrial morphology largely returned to the normal level in all the three treatment groups， with an increase in mitochondrial number （P<0.05）， improved crista integrity （P<0.05， P<0.01）， and a decreased proportion of vacuolization （P<0.05）. ConclusionAβ_1-42 oligomers can activate BV2 cells and enhance glycolytic activity in the high glucose environment. CA can reduce the expression of inflammatory factors and inhibit the activation of BV2 cells by regulating the glucose metabolism reprogramming in BV2 cells.

ObjectiveTo investigate the effects of paeoniflorin （PF） on neuroinflammation and cognitive impairment in the rat model of Alzheimer's disease （AD） and to clarify whether its mechanism is associated with regulation of the Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） signaling pathway. MethodsGlycosides related to AD-associated neuroinflammation were screened through bibliometric analysis， and the potential targets of PF were predicted through network pharmacology and molecular docking. A rat model of AD was established by intraperitoneal injection of D-galactose （100 mg·kg^-1·d^-1）. Rats were assigned into a control group， a model group， a PF （200 mg·kg^-1） group， and a donepezil （0.5 mg·kg^-1·d^-1） group， and drugs were administered by gavage for 21 days. The learning and memory abilities were evaluated by the Morris water maze （MWM）. Hematoxylin-eosin （HE） staining and Nissl staining were performed to observe hippocampal neuronal morphology. The mRNA levels of inflammatory factors were determined by Real-time quantitative polymerase chain reaction （Real-time PCR）， and the protein levels of molecules in the JAK2/STAT3 signaling pathway were determined by Western blot. ResultsCompared with the control group， the model group showed prolonged escape latency and decreased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， accompanied by increased expression of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as elevated ratios of phosphorylated （p）-JAK2/JAK2 and p-STAT3/STAT3 （P<0.01）. Compared with the model group， the PF group and donepezil group exhibited shortened escape latency and increased platform crossings and time spent in the target quadrant （P<0.05， P<0.01）， decreased expression levels of IL-1β and TNF-α， upregulated mRNA levels of interleukin-4 （IL-4） and interleukin-10 （IL-10）， and reduced ratios of p-JAK2/JAK2 and p-STAT3/STAT3 （P<0.05， P<0.01）. ConclusionPaeoniflorin can alleviate cognitive impairment and neuroinflammation in the rat model of AD by inhibiting the JAK2/STAT3 signaling pathway.

ObjectiveTo investigate the effect and underlying mechanism of the Wulao Qisun prescription on pathological new bone formation in ankylosing spondylitis （AS）. MethodsSynovial fibroblasts were isolated from the hip joints of AS patients and observed under a microscope to assess cell morphology. The cells were identified using immunofluorescence staining. The isolated AS fibroblasts were divided into blank group， low drug-containing serum group， medium drug-containing serum group， high drug-containing serum group， and positive drug group. After drug intervention， cell proliferation was measured using the cell counting kit-8 （CCK-8） assay to observe fibroblast growth and determine the optimal intervention time. Alkaline phosphatase （ALP） activity was measured using the alkaline phosphatase assay. Protein expression of osteocalcin （OCN）， osteopontin （OPN）， and runt-related transcription factor 2 （Runx2） was detected by Western blot. The mRNA expression levels of Wnt5a， β-catenin， and Dickkopf-1 （DKK-1） were measured by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsCompared with the blank group， each drug-containing serum group of Wulao Qisun prescription and the positive drug group inhibited the proliferation of AS fibroblasts and reduced ALP expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription downregulated β-catenin mRNA expression （P<0.05）. The medium and high drug-containing serum groups and the positive drug group significantly downregulated Wnt5a and β-catenin mRNA expression （P<0.05， P<0.01）， with the positive drug group showing the most pronounced effect （P<0.01）. The high drug-containing serum group and the positive drug group significantly upregulated DKK-1 mRNA expression （P<0.01）. Compared with the blank group， the low drug-containing serum group of Wulao Qisun prescription inhibited the expression of OPN and Runx2 proteins （P<0.05， P<0.01）， while the medium and high drug-containing serum groups and the positive drug group inhibited the expression of OCN， OPN， and Runx2 proteins （P<0.05， P<0.01）. ConclusionThe Wulao Qisun prescription can inhibit the proliferation and osteogenic differentiation of AS fibroblasts， thereby delaying the formation of pathological new bone in AS. The possible mechanism involves the regulation of Wnt/β-catenin-related gene expression， further inhibiting the transcription of downstream target genes.

Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.

In this study, we constructed a GLP-2R-HEK293 cell line and established a method for the determination of the in vitro biological activity of teduglutide based on HTRF, after optimizing experimental conditions and methodological verification. We also carried out relative potency detection of teduglutide pharmaceutical products using this method. The result showed that there was a quantitative-efficient relationship between the teduglutide activity and cAMP contents in GLP-2R-HEK293 cells, which conformed to four-parameter model. Method verification results of five concentrations of teduglutide (64%, 80%, 100%, 125% and 156%) met the requirements of the General Rules of Chinese Pharmacopoeia, 2020 edition, Volume IV (9401). We then analyzed the relative potency of three batches of teduglutide drug substances and three batches of drug products. The linearity, regression and parallelism of the obtained curves all fit the system suitability requirements. The relative potency of six batches of teduglutide was from 83% to 105%. In summary, the biological activity detection method established in this study was accurate, precise, simple and time-saving, which can be used for quality control of teduglutide pharmaceutical products.

The traditional Chinese medicine(TCM) industry is a crucial part of China's pharmaceutical sector and plays a strategic role in ensuring public health and promoting economic and social development. In response to the practical demand for high-quality development of the TCM industry, this paper focused on the bottlenecks encountered during the digital and intelligent transformation of TCM production systems. Specifically, it explored technical strategies and methodologies for constructing the best TCM production mode. An innovative artificial intelligence(AI)-centered technical architecture for TCM production was proposed, focusing on key aspects of production management including process modeling, state evaluation, and decision optimization. Furthermore, a series of critical technologies were developed to realize the best TCM production mode. Finally, a novel AI-driven TCM production mode characterized by a closed-loop system of "measurement-modeling-decision-execution" was presented through engineering case studies. This study is expected to provide a technological pathway for developing new quality productive forces within the TCM industry.
Artificial Intelligence ; Drugs, Chinese Herbal ; Medicine, Chinese Traditional/methods* ; Humans

OBJECTIVE: To observe the clinical efficacy of 3D printing spinal external fixator combined with McKenzie therapy for patients with lumbar dics herniation (LDH). METHODS: Sixty patients with LDH between January 2022 and January 2023 were enrolled. Among them, 30 patients were given McKinsey training. According to different treatment methods, all patients were divided into McKenzie group and McKenzie + 3D printing group, 30 patients in each group. The McKenzie group provided McKenzie therapy. The McKenzie + 3D printing group were treated with 3D printing spinal external fixation brace on the basis of McKenzie therapy. Patients in both groups were between 25 and 60 years of age and had their first illness. In the McKenzie group, there were 19 males and 11 females, with an average age of (48.57±5.86) years old, and the disease duration was (7.03 ±2.39) months. The McKenzie + 3D printing group, there were 21 males and 9 females, with an average age of (48.80±5.92) years old, and the disease duration was(7.30±2.56) months. Pain was evaluated using the visual analogue scale (VAS), and lumbar spine function was assessed using the Oswestry disability index (ODI) and the Japanese Orthopaedic Association (JOA) score. VAS, ODI and JOA scores were compared between two groups before treatment and at 1, 3, 6, 9 and 12 months after treatment. RESULTS: All patients were followed up for 12 months. The VAS for the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(6.533±0.860), (5.133±1.008), (3.933±0.868), (2.900±0.759), (2.067±0.640), (1.433±0.504), respectively. In the McKenzie group, the corresponding scores were (6.467±0.860), (5.067±1.048), (4.600±0.968), (3.533±1.008), (2.567±0.728), (1.967±0.809), respectively. The ODI of the McKenzie group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were (41.033±6.810)%, (37.933±6.209)%, (35.467±6.962)%, (27.567±10.081)%, (20.800±7.531)%, (13.533±5.158)%, respectively. For the McKenzie combined with 3D printing group, the corresponding ODI were(38.033±5.605)%, (33.000±6.192)%, (28.767±7.045)%, (22.200±5.517)%, (17.700±4.836)%, (11.900±2.771)%, respectively. The JOA scores of the McKenzie combined with 3D printing group before treatment and at 1, 3, 6, 9, and 12 months post-treatment were(8.900±2.074), (13.133±2.330), (15.700±3.583), (20.400±3.480), (22.267±3.084), (24.833±2.640), respectively. In the McKenzie group, the corresponding scores were(9.200±2.091), (12.267±2.406), (15.333±3.198), (18.467±2.240), (20.133±2.751), (22.467±2.849), respectively. Before the initiation of treatment, no statistically significant differences were observed in the VAS, ODI, and JOA scores between two groups (P>0.05). At 3, 6, 9, and 12 months post-treatment, the VAS in the McKenzie combined with 3D printing group was significantly lower than that in the McKenzie group, and the difference was statistically significant (P<0.05). The comparison of ODI between two groups at 1, 3, 6, 9, and 12 months post-treatment revealed statistically significant differences (P<0.05). At 6, 9, and 12 months post-treatment, the JOA score in the McKenzie combined with 3D printing group was significantly higher than that in the McKenzie-only group, and the difference was statistically significant (P<0.05). CONCLUSION The combination of 3D printed functional spinal external fixation brace with McKenzie therapy can significantly improve and maintain lumbar function in patients with LDH.
Humans ; Male ; Female ; Middle Aged ; Printing, Three-Dimensional ; Intervertebral Disc Displacement/surgery* ; External Fixators ; Lumbar Vertebrae/surgery* ; Adult ; Braces ; Treatment Outcome

According to the World Health Organization (WHO) manual, sperm concentration should be measured using an improved Neubauer hemocytometer, while sperm motility should be measured by manual assessment. However, in China, thousands of laboratories do not use the improved Neubauer hemocytometer or method; instead, the Makler counting chamber is one of the most widely used chambers. To study sources of error that could impact the measurement of the apparent concentration and motility of sperm using the Makler counting chamber and to verify its accuracy for clinical application, 67 semen samples from patients attending the Department of Andrology, West China Second University Hospital, Sichuan University (Chengdu, China) between 13 September 2023 and 27 September 2023, were included. Compared with applying the cover glass immediately, delaying the application of the cover glass for 5 s, 10 s, and 30 s resulted in average increases in the sperm concentration of 30.3%, 74.1%, and 107.5%, respectively (all P < 0.0001) and in the progressive motility (PR) of 17.7%, 30.8%, and 39.6%, respectively (all P < 0.0001). However, when the semen specimens were fixed with formaldehyde, a delay in the application of the cover glass for 5 s, 10 s, and 30 s resulted in an average increase in the sperm concentration of 6.7%, 10.8%, and 14.6%, respectively, compared with immediate application of the cover glass. The accumulation of motile sperm due to delays in the application of the cover glass is a significant source of error with the Makler counting chamber and should be avoided.
Humans ; Male ; Sperm Motility/physiology* ; Sperm Count ; Semen Analysis/methods* ; Spermatozoa/physiology* ; Time Factors