This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

To explore the common irritant components in different base sources of Polygonati Rhizoma(PR). A rabbit eye irritation experiment was conducted to compare the irritant effects of raw products of Polygonatum kingianum, P. officinale, and P. multiflorum. The irritant effects of different solvent extraction parts and needle crystals of PR were compared, and the irritant components were screened. The morphology and structure of the purified needle crystal of PR were observed by microscope and scanning electron microscope and characterized by X-ray diffraction. Rabbit eye irritation and mouse abdominal inflammation model were used to evaluate rabbit eye irritation scores, inflammatory mediators, inflammatory factors levels in the peritoneal exudate of mice, with the peritoneal pathological section used as indicators. The inflammatory effect of needle crystals of PR was studied, and the content of calcium oxalate in three kinds of PR was determined by HPLC. The common protein in three kinds of PR was screened and compared by double enzymatic hydrolysis in solution combined with mass spectrometry. The results showed that three kinds of PR raw products had certain irritant effects on rabbit eyes, among which P. kingianum had the strongest irritant effect. There were no obvious irritant effects in the different solvent extraction parts of P. kingianum. Compared with the blank group, the needle crystal of PR had a significant irritant effect on rabbit eyes, and the inflammatory mediators and inflammatory factors in the peritoneal exudate were significantly increased(P<0.05) in a dose-dependent manner. Meanwhile, the peritoneal tissue of mice was damaged with significant inflammatory cell infiltration after intraperitoneal injection of needle crystal, indicating that needle crystal had an inflammatory effect. Microscope and scanning electron microscope observations showed that the needle crystals of PR were slender, with a length of about 100-200 μm and sharp ends. X-ray diffraction analysis showed that the needle crystals of PR were calcium oxalate monohydrate crystals. The results of HPLC showed that the content of calcium oxalate in P. kingianum was the highest among the three kinds of PR. It was speculated that the content of needle crystal in P. kingianum was higher than that in P. officinale and P. multiflorum, which was consistent with the results of the rabbit eye irritation experiment. The results of mass spectrometry showed that ribosome inactivating protein and mannose/sialic acid binding lectin were related to inflammation and cell metabolism in all three kinds of PR. There was no obvious irritant effect in different solvent extracts of PR. The calcium oxalate needle crystal contained was the main irritant component of PR, and three kinds of PR contained common ribosome inactivating protein and mannose/sialic acid binding lectin, which may be related to the inflammatory irritant effect of PR.
Animals ; Rabbits ; Mice ; Polygonatum/chemistry* ; Drugs, Chinese Herbal/toxicity* ; Rhizome/chemistry* ; Male ; Eye/drug effects* ; Female ; Humans

Liver ischemia-reperfusion injury (LIRI) is a pathological process involving multiple injury factors and cell types, with different stages. Currently, protective drugs targeting a single condition are limited in efficacy, and interventions on immune cells will also be accompanied by a series of side effects. In the current bottleneck research stage, the multi-target and obvious clinical efficacy of Chinese medicine (CM) is expected to become a breakthrough point in the research and development of new drugs. In this review, we summarize the roles of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in various stages of hepatic ischemia-reperfusion and on various types of cells. Combined with the current research progress in reducing ROS/RNS with CM, new therapies and mechanisms for the treatment of hepatic ischemia-reperfusion are discussed.
Reperfusion Injury/drug therapy* ; Reactive Oxygen Species/metabolism* ; Reactive Nitrogen Species/metabolism* ; Humans ; Liver/drug effects* ; Animals ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology*

Objective:To retrospectively analyze the clinical features and surgical efficacy of congenital cholesteatoma （CC） and acquired cholesteatoma （AC） in children. Methods:Clinical data of 169 children with middle ear cholesteatoma were reviewed in the Department of Otorhinolaryngology Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University from January 2010 to July 2020. The clinical characteristics, stages, surgical methods, and postoperative recurrence rates were analyzed and summarized. Results:The age distribution of enrolled children ranged from 2 to 14 years. The mean age of the CC group was （5.60±2.48） years compared with （6.45±2.48） years in the AC group, and the difference was statistically significant （P<0.05）. Preoperative hearing in the CC group was （40.06±13.52） dB HL, which was better than in the AC group at （48.40±13.84） dB HL （P<0.05）. The proportion of stage Ⅰ in the CC group was lower than that in the AC group according to EAONO/JOS staging （P<0.05）. The recurrence rate after primary surgery was 19.23% （10/52） in the CC group compared with 36.29% （45/124） in the AC group （P<0.05）. The mastoid retention rates after all operations were 28.85% （15/52） in the CC group and 5.65% （7/124） in the AC group （P<0.05）. Conclusion:Compared with congenital cholesteatoma, acquired cholesteatoma in children is more aggressive and has more complications, higher postoperative recurrence rate, and less possibility of mastoid retention. Early clinical detection and treatment are required, and canal wall-down tympanoplasty should be considered in surgery.
Humans ; Cholesteatoma, Middle Ear/congenital* ; Child ; Retrospective Studies ; Child, Preschool ; Adolescent ; Male ; Female ; Recurrence ; Cholesteatoma/congenital* ; Tympanoplasty ; Treatment Outcome

Hemodynamics numerical simulation,a multidisciplinary research approach integrating fluid dynamics,clinical medicine,and computer simulation techniques,offers an objective and quantitative analysis of cardiovascular blood flow dynamics through calculating data such as flow rate,pressure,resistance,and wall stress.This review provides a comprehensive overview of the modeling methods and characteristics of numerical simulations within the cardiovascular system.Additionally,it also summarizes the research advancements and potential clinical applications of numerical simulations in the context of various cardiovascular diseases,including vascular aneurysms,aortic dissection,atherosclerosis,structural heart diseases,heart failure,ventricular assist devices,cardiogenic shock,and extracorporeal membrane oxygenation.The goal is to facilitate the deep integration of clinical medicine with engineering technologies,thereby fostering innovative solutions for the precise diagnosis and treatment of cardiovascular disease.

Objective To understand the timeliness of antiretroviral therapy (ART) in newly reported HIV/AIDS cases in Yichang from 2016 to 2022 and its influencing factors, and to provide a scientific basis for improving the timeliness of ART in Yichang City. Methods HIV/AIDS cases data from January 1, 2016 to December 31, 2022 were collected, and chi-square tests and logistic regression were used to analyze the factors influencing the timeliness of ART. Results A total of 1 126 HIV/AIDS cases were collected, with local reported cases accounting for 83.13%. The male to female ratio was 5.15:1. The median age was 42 years old (28-53 years old). 41.03% of the cases were unmarried. 38.99% of cases had a first-time CD4+T lymphocytes (CD4 cells) count < 200 cells/µL. Cases with timely first CD4 cell test accounted for 67.85%. The overall timely rate of ART from 2016 to 2022 was 57.19%, with a median time from diagnosis to initiation of ART of 20 days. There was no statistically significant difference in the trend of ART timely rate from 2016 to 2022 (P=0.251). Cases with timely first CD4 cell test were more likely to initiate ART in time (OR=3.831, 95% CI:2.454-5.981), while cases reported from other areas (OR=0.497, 95% CI:0.345-0.716) and cases with higher first CD4 cell count levels (OR_≥500=0.473, 95% CI:0.312-0.718) were less likely to initiate ART in time. Conclusion The timely rate of antiviral treatment in Yichang City needs to be further improved. High attention should be paid to cases reported from other places, cases with delayed CD4 cell testing, and cases with high CD4 cell count levels. Treatment mobilization and referral should be done well, and early detection services should be provided in time.

Background and aim:Hepatic ischemia-reperfusion injury(IRI)is a significant challenge in liver trans-plantation,trauma,hypovolemic shock,and hepatectomy,with limited effective interventions available.This study aimed to investigate the role of leukocyte cell-derived chemotaxin 2(LECT2)in hepatic IRI and assess the therapeutic potential of Lect2-short hairpin RNA(shRNA)delivered through adeno-associated virus(AAV)vectors. Materials and methods:This study analyzed human liver and serum samples from five patients under-going the Pringle maneuver.Lect2-knockout and C57BL/6J mice were used.Hepatic IRI was induced by clamping the hepatic pedicle.Treatments included recombinant human LECT2(rLECT2)and AAV-Lect2-shRNA.LECT2 expression levels and serum biomarkers including alanine aminotransferase(ALT),aspartate aminotransferase(AST),creatinine,and blood urea nitrogen(BUN)were measured.Histological analysis of liver necrosis and quantitative reverse-transcription polymerase chain reaction were performed. Results:Serum and liver LECT2 levels were elevated during hepatic IRI.Serum LECT2 protein and mRNA levels increased post reperfusion.Lect2-knockout mice had reduced weight loss;hepatic necrosis;and serum ALT,AST,creatinine,and BUN levels.rLECT2 treatment exacerbated weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN).AAV-Lect2-shRNA treatment significantly reduced weight loss,hepatic necrosis,and serum biomarkers(ALT,AST,creatinine,and BUN),indicating thera-peutic potential. Conclusions:Elevated LECT2 levels during hepatic IRI increased liver damage.Genetic knockout or shRNA-mediated knockdown of Lect2 reduced liver damage,indicating its therapeutic potential.AAV-mediated Lect2-shRNA delivery mitigated hepatic IRI,offering a potential new treatment strategy to enhance clinical outcomes for patients undergoing liver-related surgeries or trauma.

Objective To investigate the cumulative incidence of recurrence(CIR)in children with acute lymphoblastic leukemia(ALL)after treatment with the Chinese Children's Cancer Group ALL-2015(CCCG-ALL-2015)protocol and the risk factors for recurrence.Methods A retrospective analysis was conducted on the clinical data of 852 children who were treated with the CCCG-ALL-2015 protocol from January 2015 to December 2019.CIR was calculated,and the risk factors for the recurrence of B-lineage acute lymphoblastic leukemia(B-ALL)were analyzed.Results Among the 852 children with ALL,146(17.1%)experienced recurrence,with an 8-year CIR of 19.8%±1.6%.There was no significant difference in 8-year CIR between the B-ALL group and the acute T lymphocyte leukemia group(P>0.05).For the 146 children with recurrence,recurrence was mainly observed in the very early stage(n=62,42.5%)and the early stage(n=46,31.5%),and there were 42 children with bone marrow recurrence alone(28.8%)in the very early stage and 27 children with bone marrow recurrence alone(18.5%)in the early stage.The Cox proportional-hazards regression model analysis showed that positive MLLr fusion gene(HR=4.177,95%CI:2.086-8.364,P<0.001)and minimal residual disease≥0.01%on day 46(HR=2.013,95%CI:1.163-3.483,P=0.012)were independent risk factors for recurrence in children with B-ALL after treatment with the CCCG-ALL-2015 protocol.Conclusions There is still a relatively high recurrence rate in children with ALL after treatment with the CCCG-ALL-2015 protocol,mainly bone marrow recurrence alone in the very early stage and the early stage,and minimal residual disease≥0.01%on day 46 and positive MLLr fusion gene are closely associated with the recurrence of B-ALL.

Objective:To comprehensively analyze the numbers of involved chromosomes and breakpoints and the clinical phe-notypes of the patients with complex chromosome rearrangement(CCR).Methods:We selected 23 745 patients with abnormal fer-tility seeking medical care in the Center of Reproductive Medicine of Peking University Third Hospital from 2011 to 2015,and analyzed their peripheral blood chromosomal karyotypes using G-banding,C-banding and fluorescence in situ hybridization(FISH).Results:A total of 28 CCR carriers(0.118％ )were detected among the23 745 patients with abnormal fertility,including 18 males mainly with azoospermia or oligoasthenospermia and 10 females mainly with infertility,recurrent abortion,embryo termination and abnormal birth.Of the 28 cases of CCR,tripartite rearrangement was found in9(32.14％ ),double translocation in7(25％ )and special transloca-tion in 12(42.86％ ).CCR carrier-related chromosomes were all involved but chromosomes 12 and 19,while 2 and 5 were involved most frequently.Conclusion:At present,the incidence of CCR is low.CCR carriers with normal phenotypes are often found because of reproductive problems,and their low chance of having a normal baby necessitates the use of preimplantation genetic test to improve the rate of live birth.Due to the diversity of the chromosomes and breakpoints involved in CCR,it is crucial to give each CCR carrier precise genetic counseling.

Stent under-expansion is a relatively common situation during coronary intervention procedure,which can lead to serious consequences such as stent restenosis,stent thrombosis and stent rupture.How to early identify and deal with stent under-expansion has achieved widespread attention in recent years.Intraluminal imaging guided percutaneous coronary intervention plays an important role in the prevention of stent under-expansion.Besides,recent studies have demonstrated the feasibility of shockwave balloon,excimer laser coronary atherectomy and rotational atherectomy in dealing with stent under-expansion.This paper reviews the pathophysiology,intraluminal imaging evaluation and management of stent under-expansion to provide a reference for coronary intervention.