ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveTo evaluate the therapeutic effects of Huanglian Jiedutang on cerebral infarction injury in a mouse model of middle cerebral artery occlusion （MCAO） and to explore its mechanism of action on oligodendrocytes， particularly its potential in myelin repair. MethodsMultiple experimental approaches were used to evaluate cerebral ischemic injury and the effects of drug intervention. Laser speckle imaging was used to detect changes in cerebral blood flow， 2，3，5-Triphenyltetrazolium chloride （TTC） staining was used to measure infarct volume， and neurological function was scored according to the Zea-Longa criteria. Brain tissues were routinely embedded in paraffin and subjected to HE and Nissl staining to observe tissue structure and neuronal damage. Animals were divided into a sham group （n=24）， model group （n=24）， Huanglian Jiedutang group （n=24）， and Ginkgo biloba extract （GBE） group （n=18）. After 1 week of acclimatization， intragastric administration was initiated. The sham and model groups received normal saline， the Huanglian Jiedutang group was administered 1.82 g·kg^-1， and the GBE group was administered 0.432 g·kg^-1 after preparation as a 2.16 g·L^-1 solution. All groups were treated for 5 consecutive days at a dose of 0.2 mL·（10 g）^-¹·d^-¹. The MCAO model was established after the final administration on day 6. Single-cell RNA sequencing was used to analyze brain tissue cellular composition and changes in oligodendrocyte subpopulations. Distinct subpopulations were identified by Uniform manifold approximation and projection （UMAP） dimensionality reduction and unsupervised clustering， and marker gene expression was analyzed. Pathway enrichment and causal inference were further performed using IPA. Finally， real-time quantitative PCR was used to verify mRNA expression changes of myelin-related genes. ResultsCompared with the sham group， the model group showed significantly increased neurological function scores （P<0.01）， significantly impaired blood flow （P<0.01）， significantly enlarged cerebral infarct area （P<0.01）， and pathological changes including disordered cortical structural arrangement， aggravated cytoplasmic vacuolization， and increased Nissl bodies. Compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly decreased neurological function scores （P<0.01）， markedly restored blood flow levels （P<0.01）， significantly reduced cerebral infarct area （P<0.01）， and improvement in cortical structural disorder， alleviation of cytoplasmic vacuolization， and a reduction in Nissl bodies. Single-cell data showed that a myelin-associated oligodendrocyte （Mye-OL） subpopulation existed among oligodendrocytes， which was closely related to myelin generation. Compared with the sham group， the number of Mye-OL cells decreased in the model group. Compared with the model group， the number of Mye-OL cells increased in the Huanglian Jiedutang group. This subpopulation promoted the expression of myelin-related genes， including MOG， MBP， and MAG， via transcription factors such as OLIG1， OLIG2， NKX2-2， and SOX10， thereby regulating myelin generation， restoring cognition， and exerting therapeutic effects on acute cerebral infarction. Compared with the sham group， the mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 were significantly downregulated in the model group （P<0.01）， and the mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG， were also significantly downregulated （P<0.01）. In contrast， compared with the model group， the Huanglian Jiedutang and GBE groups showed significantly upregulated mRNA expression levels of OLIG1， OLIG2， NKX2-2， and SOX10 （P<0.01）， and significantly upregulated mRNA expression levels of myelin-related genes， including MOG， MBP， and MAG （P<0.01）. ConclusionHuanglian Jiedutang exerts therapeutic effects on acute cerebral infarction by regulating the OLIG1/2-NKX2-2-SOX10 signaling pathway to promote myelin generation by Mye-OL cells.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Acute-on-chronic liver failure （ACLF） is an acute and critical illness with a high short-term mortality rate， and current therapies mainly focus on elimination of causes， organ support， and prevention of complications. Although liver transplantation is the most effective treatment modality， its clinical application is limited， and traditional Chinese medicine has shown significant advantages and characteristics in the treatment of ACLF. In traditional Chinese medicine， ACLF is classified into the same category as diseases such as “jaundice”， and unlike traditional jaundice which is mostly characterized by excess and heat syndromes， the syndrome of ACLF has gradually transformed from Yang jaundice to Yin jaundice due to the changing disease spectrum of ACLF. With reference to the pathogenesis of ACLF in Western medicine and traditional Chinese medicine theories， this article discusses the essential pathogenesis of ACLF in traditional Chinese medicine， explores the evolution of ACLF syndromes， and reviews the research advances in the clinical efficacy and mechanisms of traditional Chinese medicine based on the three-factor differentiation-based treatment of damp-heat， blood stasis-heat， and spleen deficiency， as well as the safety of spleen-strengthening and Yang-warming drugs in the clinical treatment of ACLF， in order to provide ideas， methods， and evidence for the application of traditional Chinese medicine in ACLF.

Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Objective:To explore the significance of any correlation between the cost of the rehabilitation provided to stroke survivors during their hospitalization and the functional levels attained, and to analyze factors influencing that correlation.Methods:The International Classification of Functioning, Disability and Health Rehabilitation Set (ICF-RS) was used to evaluate the functioning of 304 stroke survivors on their days of hospital admission and discharge, as well as on their 10th day in hospital. The cost of their rehabilitation was computed, and demographic and clinical data were collected. A generalized estimation equation was used to analyze the changes in dysfunction with time and its risk factors. The relationship between functional levels and rehabilitation cost and its influencing factors were analyzed.Results:Length of stay, age≥60 and hemorrhagic stroke were significant risk factors for greater dysfunction among the stroke survivors. On the 10th day in hospital and the day before discharge (the 18th day), the frequency of severe dysfunction had decreased. The significant predictors of increased cost were severe or moderate dysfunction, the stage of stroke (sub-acute stage), and non-first rehabilitation.Conclusion:Functional level is a useful predictor of rehabilitation cost. It is influenced by the stage of stroke and non-first rehabilitation.

Objective To investigate the efficacy and safety of self-help inflatable balloon in the treatment of refractory benign upper digestive tract stricture.Methods From November 2022 to February 2024,10 patients with refractory benign upper digestive tract stricture underwent self-help inflatable balloon were retrospectively analyzed.Preoperative treatment,intraoperative and postoperative complications,dysphagia score before and after surgery,wearing time of external self-help inflatable balloon,and the clinical efficacy were evaluated.Results All the 10 patients received self-help inflatable balloon treatment.No complications such as bleeding and perforation occurred in all patients during the wearing of the balloon.The placement time of the balloon was 60～180 d,and the average wearing time was 104.9 d.Before surgery,nine cases had a stricture segment length less than 2 cm,and one case had a stricture segment length of 6 cm.The dysphagia score before surgery was(3.60±0.52),and the dysphagia score after removal of the self-help inflatable balloon was(0.60±0.52),and there was statistical significance in preoperative and postoperative comparison(P＜0.05).The dysphagia score 3 months after removal of the external self-help inflatable balloon was(0.70±0.48),there was no significant difference in dysphagia score between the day after surgery and 3 months after surgery(P＞0.05).The diameter of the stricture before and after operation was(5.09±2.02)mm and(10.35±0.73)mm respectively,and the difference was statistically significant(P＜0.05).Sore throat,wing of nose pain and balloon displacement were the most common adverse events,with 30.0％(3/10),50.0％(5/10)and 70.0％(7/10),respectively.Conclusion It is safe,effective and feasible to treat refractory benign upper digestive tract stricture with self-help inflatable balloon in vitro.It is worthy for clinical application.

Objective:To establish an early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy and to verify its predictive efficacy, so as to provide reference for formulating strategies to prevent oral infections.Methods:A retrospective study was conducted to select 288 patients with acute leukemia undergoing chemotherapy from January 2021 to January 2023 in Hematology Hospital of Chinese Academy of Medical Sciences (Institute of Hematology, Chinese Academy of Medical Sciences) as the training set. According to whether they developed oral infection after chemotherapy, they were divided into the infected group and the non-infected group. The risk factors of oral infection in patients with acute leukemia undergoing chemotherapy were investigated, and a risk warning model was established. A total of 246 acute leukemia undergoing chemotherapy patients admitted to the same hospital from February 2023 to February 2024 were selected as the validation set to conduct external verification of the model.Results:The oral infection rate was 19.44% (56/288) in the training set. There were 21 males and 35 females in the infected group (56 cases), with 49 cases<60 years old and 7 cases ≥60 years old. There were 102 males and 130 females in the non infected group (232 cases), with 196 cases<60 years old and 36 cases ≥60 years old. Multivariate analysis showed that neutrophil count <1.5×10 9/L, nutritional risk screening 2002≥3 points, high-dose of methotrexate, antibiotic types ≥3, poor oral self-cleaning habits, oral pH ≤6.5 were the risk factors for oral infection in patients with acute leukemia undergoing chemotherapy ( OR values were 2.716-10.074, all P<0.05). Based on this, the risk early warning model was as follows: Logit ( P)=-5.849+2.310× neutrophil count <1.5×10 9/L+1.363× nutritional risk screening 2002≥3 points +1.150× high-dose methotrexate +1.132× antibiotic types ≥3 + 1.044× oral pH ≤6.5 + 0.999× poor oral self-cleaning habits. The area under receiver operator characteristics curves (ROC) curve of this model Logit ( P) was 0.892, the maximum approximate entry index was 0.653, the sensitivity was 0.804, and the specificity was 0.849. Hosmer-Lemeshow test results indicated that χ2=4.91, P=0.768. For external validation, the goodness of fit test results were χ2=6.47, P=0.595. The area under ROC curve was 0.884, the sensitivity was 0.832, and the specificity was 0.825. Conclusions:The established early warning model of oral infection risk in patients with acute leukemia undergoing chemotherapy has good predictive value, which is helpful for medical staff to conduct early risk assessment of oral infection in such patients, and formulate countermeasures to reduce the incidence and improve the treatment effect of the disease.

OBJECTIVE: To systematically search and integrate the best evidence for early rehabilitation of ICU-acquired swallowing dysfunction (ICU-ASD) using evidence-based medicine methods, providing high-quality evidence-based support for intensive care unit (ICU) healthcare professionals in implementing early rehabilitation assessment and intervention strategies for ICU-ASD. METHODS: The systematic search was conducted according to the "6S" pyramid evidence model. Multiple authoritative databases and resources were comprehensively searched, including: National Guideline Clearinghouse (NGC), National Institute for Health and Care Excellence (NICE), Canadian Medical Association Clinical Practice Guidelines Library (CMACPGL), New Zealand Guidelines Group (NZGG), Guidelines International Network (GIN), Registered Nurses' Association of Ontario (RNAO), Scottish Intercollegiate Guidelines Network (SIGN), PubMed/Medline, Cochrane Library, Embase, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, JBI Evidence-Based Health Care Database, Physiotherapy Evidence Database (PEDro), Chinese Medical Pulse Guidelines Website, SinoMed, CNKI, Wanfang Data, UpToDate, BMJ Best Practice, and professional association websites. The search encompassed guidelines, expert consensus statements, original studies [including cohort studies, quasi-experimental studies, and randomized controlled trials (RCT)], systematic reviews, and evidence summaries related to the prevention and management of ICU-ASD. The search period was limited from the inception of each database to November 30, 2024. The best evidence for early rehabilitation of ICU-ASD was summarized. The quality assessment of the literature and the extraction and synthesis of evidence were independently performed by two researchers with expertise in evidence-based medicine methodology. RESULTS: A total of 16 articles were included, consisting of 1 clinical decision-making study, 1 cohort study, 2 guidelines, 2 RCTs, 6 systematic reviews, 1 evidence summary, 2 expert consensuses, and 1 expert opinion. Following quality assessment, all 16 articles were incorporated into the analysis. For the early rehabilitation of ICU-ASD, five major themes were ultimately identified and 25 best evidence items were summarized, focusing on: multidisciplinary collaboration, swallowing screening and assessment, rehabilitation interventions, dietary and nutritional management, and oral hygiene. CONCLUSIONS The evidence summary provides individualized rehabilitation strategies for ICU-ASD patients, but their implementation still needs to be adapted to China's clinical practice context and patient preferences.
Humans ; Deglutition Disorders/etiology* ; Intensive Care Units ; Evidence-Based Medicine