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.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Objective:To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma.Methods:A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor.Results:① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group ( P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group ( P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower ( P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group ( P=0.002), whereas the incidence of grade 3 diarrhea was lower ( P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea ( P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group ( P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group ( P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group ( P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups ( P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively ( P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively ( P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively ( P=0.373) . Conclusion:In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

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 investigate the effects and underlying mechanism of Toona sinensis bark extract(TAE)on the colon mucosal barrier and gut microbiota in mice with ulcerative colitis(UC)induced by dextran sulfate sodium(DSS).METHODS:Sixty C57BL/6J mice were randomly assigned to control,model,and mesalazine(0.2 g/kg)groups,as well as TAE groups(low,medium,and high-doses equal to crude drug concentrations of 2.3,4.6 and 9.2 g/kg,respectively).The UC model was induced by drinking of 2.5％DSS,and mean while the drugs were administered for 10 days.The mice were then evaluated in terms of weight,disease activity index(DAI),colon length,spleen index,and pathological changes in the colon tissues.In addition,the level of apoptosis in colon tissues was assessed by terminal de-oxynucleotidyl transferase dUTP nick-end labeling(TUNEL)fluorescence staining,and the expression of related proteins was evaluated by Western blot,levels of inflammatory factors were determined by enzyme-linked immunosorbent assays(ELISA),and the activities of total superoxide dismutase(T-SOD)and catalase(CAT)and malondialdehyde(MDA)content were assessed by biochemical assays.Furthermore,the constitution and diversity of the gut microbiota were inves-tigated by 16S rRNA gene sequencing.RESULTS:Compared with the control group,mice in the model group showed significantly reduced body weights(P<0.01),and the colon length was shortened significantly(P<0.05).Marked in-creases in the DAI and spleen index were observed(P<0.01),along with severe damage to the colon mucosa(P<0.01).Mechanistically,the level of intestinal epithelial cell apoptosis was significantly raised(P<0.01).The model group showed markedly reduced expression of occludin and claudin-1(P<0.01),the level of IL-10,and activities of T-SOD and CAT in the colon tissues(P<0.01).While the levels of IL-6,IL-1β,TNF-α,and the MDA content were increased signif-icantly(P<0.05).The abundance and diversity of the gut microbiota were decreased in the model group(P<0.05).Com-pared with the model group,all these indicators were ameliorated by the administration of TAE(P<0.05).The abundance of pathogenic bacteria,including Proteobacteria and Escherichia-Shigella,was decreased remarkably(P<0.05),while that of probiotics,including Bacteroidota and Muribaculaceae,were increased significantly(P<0.05).The abundance and diversity of the gut microbiota were increased.CONCLUSION:Taken together,Toona sinensis bark alcohol extract can alleviate damage to the intestinal mucosa by suppressing the apoptosis of intestinal epithelial cell,reducing the inflam-matory response,and mitigating oxidative stress.Treatment with TAE could also maintain the homeostasis of the gut micro-biota by regulating the abundance,ultimately meliorate the function of intestinal mucosal barrier.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.
Humans ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Prescriptions ; Drug Combinations ; Diabetic Angiopathies/drug therapy* ; Data Mining ; Diabetes Mellitus/drug therapy*

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.
Humans ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal/chemistry* ; Asteraceae/chemistry* ; Lung Neoplasms/drug therapy*

A quantitative proton nuclear magnetic resonance(qHNMR) method was established to determine the glucose content in commercially available Massa Medicata Fermentata(MMF) products and explore the variations of glucose content in MMF products during processing. The qHNMR spectrum of MMF in deuterium oxide was obtained with 2,2,3,3-d_4-3-(trimethylsilyl) propionate sodium salt as the internal standard substance. With the doublet peaks of terminal hydrogen of glucose with chemical shift at δ 4.65 and δ 5.24 as quantitative peaks, the content of glucose in MMF samples was determined. The glucose content showed a good linear relationship within the range of 0.10-6.44 mg·mL~(-1). The relative standard deviations(RSDs) of precision, stability, repeatability, and recovery for determination were all less than 2.3%. The glucose content varied in different commercially available MMF samples, which were associated with the different fermentation days, wheat bran-to-flour ratios, and processing methods. The glucose content in MMF first increased and then decreased over the fermentation time. Compared with the MMF products fermented with wheat bran or flour alone, the products fermented with both wheat bran and flour had increased glucose. The glucose content of bran-fried MMF was slightly lower than that of raw MMF, while the glucose content in charred MMF was extremely low. In conclusion, the qHNMR method established in this study is simple, fast, and accurate, serving as a new method for determining the glucose content in MMF. Furthermore, this study clarifies the variations of glucose content in MMF during processing, which can not only indicate the processing degree but also provide a scientific basis for revealing the fermentation mechanism and improving the quality control of MMF.
Protons ; Drugs, Chinese Herbal/chemistry* ; Dietary Fiber ; Magnetic Resonance Spectroscopy