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.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

Background: and Purpose Symptomatic intracranial hemorrhage (sICH) following endovascular thrombectomy (EVT) is a severe complication associated with adverse functional outcomes and increased mortality rates. Currently, a reliable predictive model for sICH risk after EVT is lacking. Methods: This study used data from patients aged ≥20 years who underwent EVT for anterior circulation stroke from the nationwide Taiwan Registry of Endovascular Thrombectomy for Acute Ischemic Stroke (TREAT-AIS). A predictive model including factors associated with an increased risk of sICH after EVT was developed to differentiate between patients with and without sICH. This model was compared existing predictive models using nationwide registry data to evaluate its relative performance. Results: Of the 2,507 identified patients, 158 developed sICH after EVT. Factors such as diastolic blood pressure, Alberta Stroke Program Early CT Score, platelet count, glucose level, collateral score, and successful reperfusion were associated with the risk of sICH after EVT. The TREAT-AIS score demonstrated acceptable predictive accuracy (area under the curve [AUC]=0.694), with higher scores being associated with an increased risk of sICH (odds ratio=2.01 per score increase, 95% confidence interval=1.64–2.45, P<0.001). The discriminatory capacity of the score was similar in patients with symptom onset beyond 6 hours (AUC=0.705). Compared to existing models, the TREAT-AIS score consistently exhibited superior predictive accuracy, although this difference was marginal. Conclusions The TREAT-AIS score outperformed existing models, and demonstrated an acceptable discriminatory capacity for distinguishing patients according to sICH risk levels. However, the differences between models were only marginal. Further research incorporating periprocedural and postprocedural factors is required to improve the predictive accuracy.

ObjectiveTo investigate the role of silent information regulatory protein （SIRT6）/hypoxia-inducible factor-1α （HIF-1α） pathway in regulating the reprogramming of glucose metabolism in ulcerative colitis （UC） and the mechanism of intervention of Shaoyaotang. MethodsForty-eight c57bL/6 mice were randomly divided into a blank group， a model group， a Mesalazine group （0.42 g·kg^-1）， a Shaoyaotang group （31.08 g·kg^-1）， an inhibitor group （OSS-128167， 50 mg·kg^-1）， and an inhibitor + Shaoyaotang group （50 mg·kg^-1 OSS-128167 + 31.08 g·kg^-1 Shaoyaotang）. A UC model was established by the administration of 2.5% dextran sulfate sodium （DSS） solution for mice in other groups for 7 d， except for the blank group. The mice in each group were treated with saline， Mesalazine， Shaoyaotang， inhibitor， and inhibitor + Shaoyaotang， respectively， for 7 d. The mice were necropsied 24 h after the last administration of the drug. The blood was collected from the orbital region， and colon tissue was taken. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was employed to detect serum interleukin （IL）-10， IL-17， and IL-6 levels. A biochemical method was used to detect glucose and lactate dehydrogenase A （LDHA） levels. Immunohistochemistry （IHC） was employed to detect IL-22 and transforming growth factor-β₁ （TGF-β₁） levels in colon tissue， and Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to detect relative protein and mRNA expressions of SIRT6， HIF-1α， and LDHA. ResultsCompared with those of the blank group， disease activity index （DAI） scores of mice in the model group and inhibitor group were significantly increased （P<0.01）. The length of colon tissue was significantly shortened， and colon tissue was congested and eroded. The pathohistological scores were significantly increased （P<0.01）. The levels of serum inflammatory factors IL-17 and IL-6 were significantly elevated， and the levels of IL-10 were significantly decreased （P<0.01）. The protein expressions of IL-22 and TGF-β₁ were significantly reduced in colon tissue （P<0.01）. The relative protein and mRNA expressions of SIRT6 were significantly decreased （P<0.01）， and the relative protein and mRNA expressions of HIF-1α and LDHA and the contents of glucose and lactate were significantly elevated （P<0.01）. The level of inflammation in the colon of the mice in the inhibitor group was more severe than that in the model group （P<0.01）. Compared with the model group， the Mesalazine group， the Shaoyaotang group， and the inhibitor + Shaoyaotang group showed reduced colonic injury， significant decrease in serum IL-17 and IL-6， significant increase in IL-10 （P<0.01）， significant increase in the protein expressions of IL-22 and TGF-β₁ in colon tissue （P<0.01）， significant increase in the protein expressions of SIRT6 and the relative mRNA expressions （P<0.01）， and significant reduction in the protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate （P<0.01）. Compared with those in the Shaoyaotang group， the serum IL-17 and IL-6 were significantly increased， and IL-10 was significantly decreased in the inhibitor + Shaoyaotang group （P<0.01）. The protein expressions of IL-22 and TGF-β₁ in colon tissue were significantly decreased （P<0.01）. The expressions of SIRT6 protein and the relative mRNA expressions were significantly decreased （P<0.01）. The protein expressions of HIF-1α and LDHA， the relative mRNA expressions， and the contents of glucose and lactate were significantly elevated （P<0.01）. However， the difference between the Shaoyaotang group and the Mesalazine group was not significant. ConclusionShaoyaotang can effectively treat DSS-induced mice with UC through the SIRT6/HIF-1α pathway， and its mechanism of action may be related to the regulation of the SIRT6/HIF-1α pathway and glucose metabolism reprogramming and the inhibition of glycolysis.

Background: Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results: In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation ­(SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen ­(PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide ­(PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Background: Despite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine.Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of trans‑ planted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency. Results: In this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within sevendays after the injury, we found that arterial blood oxygen saturation ­(SpO2 ) significantly decreased to 83.7%, partial pressure of arterial oxygen ­(PaO2 ) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide ­(PaCO2 )amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A his‑ tological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7. Conclusions This modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Forsythia suspensa is a traditional Chinese medicine and a commonly used landscaping plant. Its dried fruit is used in medicine for its functions of clearing heat, removing toxins, reducing swelling, dissipating masses, and dispersing wind and heat. It possesses extremely high medicinal and economic value. However, the genetic differentiation and diversity of its wild populations remain unclear. In this study, chloroplast genome sequences were obtained from 15 wild individuals of F. suspensa using high-throughput sequencing technology. The sequence characteristics and intraspecific variations were analyzed. The results were as follows:(1) The full length of the F. suspensa chloroplast genome ranged from 156 184 to 156 479 bp, comprising a large single-copy region, a small single-copy region, and two inverted repeat regions. The chloroplast genome encoded a total of 132 genes, including 87 protein-coding genes, 37 tRNA genes, and 8 rRNA genes.(2) A total of 166-174 SSR loci, 792 SNV loci, and 63 InDel loci were identified in the F. suspensa chloroplast genome, indicating considerable genetic variation among individuals.(3) Population structure analysis revealed that F. suspensa could be divided into five or six groups. Both the population structure analysis and phylogenetic reconstruction results indicated significant genetic variation within the wild populations of F. suspensa, with no obvious correlation between intraspecific genetic differentiation and geographical distribution. This study provides new insights into the genetic diversity and differentiation within F. suspensa species and offers additional references for the conservation of species diversity and the utilization of germplasm resources in wild F. suspensa.
Genome, Chloroplast ; Forsythia/classification* ; Phylogeny ; Genetic Variation ; Chloroplasts/genetics* ; Microsatellite Repeats

This study aims to explore the protective effect of Chaihu Jia Longgu Muli Decoction on rats with heart failure after myocardial infarction, and to clarify its possible mechanisms, providing a new basis for basic research on the mechanism of classic Chinese medicinal formula-mediated inflammatory response in preventing and treating heart failure induced by apoptosis after myocardial infarction. A heart failure model after myocardial infarction was established in rats by coronary artery ligation. The rats were divided into sham group, model group, and low, medium, and high-dose groups of Chaihu Jia Longgu Muli Decoction, with 10 rats in each group. The low-dose, medium-dose, and high-dose groups of Chaihu Jia Longgu Muli Decoction were given 6.3, 12.6, and 25.2 g·kg~(-1) doses by gavage, respectively. The sham group and model group were given an equal volume of distilled water by gavage once daily for four consecutive weeks. Cardiac function was assessed using color Doppler echocardiography. Myocardial pathology was detected by hematoxylin-eosin(HE) staining, apoptosis was measured by TUNEL assay, and mitophagy was observed by transmission electron microscopy. The levels of tumor necrosis factor-α(TNF-α), interleukin(IL)-1β, and N-terminal pro-B-type natriuretic peptide(NT-proBNP) in serum were detected by enzyme-linked immunosorbent assay(ELISA). The expression of apoptosis-related proteins B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), and cleaved caspase-3 was detected by Western blot. Additionally, the expression of phosphorylated nuclear transcription factor-κB(NF-κB) p65(p-NF-κB p65)(upstream) and nuclear factor kappa B inhibitor alpha(IκBα)(downstream) in the NF-κB signaling pathway was assessed by Western blot. The results showed that compared with the sham group, left ventricular ejection fraction(LVEF) and left ventricular short axis shortening(LVFS) in the model group were significantly reduced, while left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD) increased significantly. Myocardial tissue damage was severe, with widened intercellular spaces and disorganized cell arrangement. The apoptosis rate was increased, and mitochondria were enlarged with increased vacuoles. Levels of TNF-α, IL-1β, and NT-proBNP were elevated, indicating an obvious inflammatory response. The expression of pro-apoptotic factors Bax and cleaved caspase-3 increased, while the anti-apoptotic factor Bcl-2 decreased. The expression of p-NF-κB p65 was upregulated, and the expression of IκBα was downregulated. In contrast, the Chaihu Jia Longgu Muli Decoction groups showed significantly improved of LVEF, LVFS and decreased LVEDD, LVESD compared to the model group. Myocardial tissue damage was alleviated, and intercellular spaces were reduced. The apoptosis rate decreased, mitochondrial volume decreased, and the levels of TNF-α, IL-1β, and NT-proBNP were lower. The expression of pro-apoptotic factors Bax and cleaved caspase-3 decreased, while the expression of the anti-apoptotic factor Bcl-2 increased. Additionally, the expression of p-NF-κB p65 decreased, while IκBα expression increased. In summary, this experimental study shows that Chaihu Jia Longgu Muli Decoction can reduce the inflammatory response and apoptosis rate in rats with heart failure after myocardial infarction, which may be related to the regulation of the IκBα/NF-κB signaling pathway.
Animals ; Apoptosis/drug effects* ; Drugs, Chinese Herbal/administration & dosage* ; Rats ; Myocardial Infarction/physiopathology* ; Male ; NF-kappa B/genetics* ; Heart Failure/etiology* ; Rats, Sprague-Dawley ; Signal Transduction/drug effects* ; NF-KappaB Inhibitor alpha/genetics* ; Humans ; Tumor Necrosis Factor-alpha/genetics*

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.
Medicine, Chinese Traditional/standards* ; Humans ; Consensus ; Drugs, Chinese Herbal/therapeutic use* ; Surveys and Questionnaires

By employing the analytic hierarchy process(AHP), the CRITIC method(a weight determination method based on indicator correlations), and the AHP-CRITIC hybrid weighting method, the weight coefficients of evaluation indicators were determined, followed by a comprehensive score comparison. The grey correlation analysis was then performed to analyze the results calculated using the hybrid weighting method. Subsequently, a backpropagation-artificial neural network(BP-ANN) model was constructed to predict the extraction process parameters and optimize the extraction process for Shenxiong Huanglian Jiedu Granules(SHJG). In the extraction process, an L_9(3~4) orthogonal experiment was designed to optimize three factors at three levels, including extraction frequency, water addition amount, and extraction time. The evaluation indicators included geniposide, berberine, ginsenoside Rg_1 + Re, ginsenoside Rb_1, ferulic acid, and extract yield. Finally, the optimal extraction results obtained by the orthogonal experiment, grey correlation analysis, and BP-ANN method were compared, and validation experiments were conducted. The results showed that the optimal extraction process involved two rounds of aqueous extraction, each lasting one hour; the first extraction used ten times the amount of added water, while the second extraction used eight times the amount. In the validation experiments, the average content of each indicator component was higher than the average content obtained in the orthogonal experiment, with a higher comprehensive score. The optimized extraction process parameters were reliable and stable, making them suitable for subsequent preparation process research.
Drugs, Chinese Herbal/analysis* ; Neural Networks, Computer