Objective: To observe the clinical efficacy and safety of Yiqi Tongluo Decoction in the intervention of early traditional Chinese medicine (TCM) syndromes after ischemic cerebrovascular disease (ICVD) intervention. Methods: From October 2020 to July 2023, a randomized, double-blind, placebo-controlled study was conducted to include 60 patients with qi deficiency, blood stasis, and phlegm obstruction syndrome after ICVD interventional therapy. They were assigned to the Yiqi Tongluo Decoction treatment group (30 cases) and the TCM placebo routine treatment control group (30 cases) according to the randomized block design. Both groups received routine standardized treatment of Western medicine, including dual antiplatelet, lipid regulation, and control of risk factors for cerebrovascular disease. The treatment group was treated with Yiqi Tongluo Decoction based on the control group. The course of treatment was 60 days and follow-up was carried out 2 and 6 months after the operation. The improvement of qi deficiency syndrome, blood stasis syndrome, phlegm syndrome score and TCM syndrome score, modified Rankin score (mRS), Barthel index (BI) score, Fatty acid-binding protein 4 (FABP4) level, incidence of transient ischemic attack (TIA) and ischemic stroke (IS) and incidence of adverse reactions, Head and neck CT angiography (CTA) or digital subtraction angiography (DSA) examination were collected. The clinical efficacy of the patients 2 months after the operation was taken as the main outcome index to preliminarily evaluate the early and long-term efficacy of Yiqi Tongluo Decoction after the ICVD intervention. The early and long-term clinical efficacy and safety of Western medicine standardized treatment combined with TCM Yiqi Tongluo Decoction on patients with qi deficiency, blood stasis and phlegm obstruction syndrome after ICVD intervention were evaluated. The safety of Yiqi Tongluo Decoction in the treatment of patients after ICVD intervention with white blood cell (WBC), C-reactive protein (CRP), fibrinogen (FIB), plasminogen time (PT), recurrence of cerebral ischaemia and restenosis in patients at 2 and 6 months after treatment were evaluated. Results: Compared to the control group, the TCM syndrome scores for qi deficiency, blood stasis and phlegm syndrome in the treatment group reduced significantly, the clinical efficacy improved significantly, the mRS score and FABP4 were reduced, and the BI score was increased. Adverse events such as cerebral ischaemia were fewer in the treatment group than in the control group, but the difference was not statistically significant; levels of CRP, WBC and PT were reduced, and levels of FIB were reduced at 6 months post-treatment, all P<0.01, and images were intuitively compared. The treatment group was superior to the control group. Conclusion Yiqi Tongluo Decoction combined with Western medicine standard treatment can improve the early clinical efficacy of ICVD patients with qi deficiency, blood stasis and phlegm obstruction syndrome after interventional surgery, improve neurological impairment and daily living ability, reduce the state of qi deficiency syndrome, blood stasis syndrome and phlegm syndrome after interventional surgery, and improve the clinical efficacy of TCM. At the same time, it can reduce the level of FABP4, the target of atherosclerosis and restenosis after interventional surgery, reduce the level of inflammation after interventional surgery in patients with ICVD, regulate coagulation function, and reduce the incidence of long-term recurrence of cerebral ischemia after interventional surgery, with good safety.

Aim To evaluate the hypolipidemic effect of the total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) on hyperlipidemic golden hamsters and explore its regulatory effect on intestinal flora. Methods Sixty hamsters were randomly divided into a control group, a model group, a positive drug group, LRTPG-L group, LRTPG-M group, and LRTPG-H group. After the successful induction of the model by high-fat diet, the animals were continuously administered for four weeks, and their blood lipids and liver lipids were detected. The formed feces from the colorectal region of the hamsters in the control group, model group and LRTPG-H group were collected for 16S rDNA sequencing. Results LRTPG reduced serum TG, TC, LDL-C and liver TG, TC concentrations significantly in hyperlipidemic hamsters. The results of the intestinal microbiota sequencing showed that compared to the control group, LRTPG significantly decreased the relative abundance of the phylum Firmicutes and increased the relative abundance of the phylum Bacteroidetes and Verrucomicrobia (P < 0.01) at the phylum level. At the family level, LRTPG significantly increased the relative abundance of Christensenellaceae, Peptococcaceae, and Verrucomicrobiaceae (P < 0.05 or P < 0.01). At the genus level, LRTPG significantly increased the relative abundance of Oscillospira, Oscillibacter, Flavonifractor and Akkermansiaceae (P < 0.05 or P < 0.01). These changes in the flora were beneficial to the hypolipidemic effect of LRTPG. Conclusion LRTPG may exert its hypolipidemic effect by improving the intestinal flora disorder caused by a high-fat diet in golden hamsters.

In this study, fluvoxamine maleate sustained-release pellet system tablets were prepared and were used to evaluate their release behaviors in vitro. Fluvoxamine maleate pellets were prepared using centrifugal-spherization method and coated by fluidized bed as bottom-spray. The multi-unit sustained-release pellets and appropriate excipients for prescription volumes were mixed uniformly and then compressed to tablets. Screening and determining the optimal formulation of drug loaded pellets through L8 (2⁴) Taguchi experiment. Using Minitab software to design a DOE experiment with 2⁴ partial factors, including material temperature, fan speed, atomization pressure, and spray rate to optimize the bottom spray coating process. Taking monostearate glycerol ester with a particle size of 24-40 mesh as the main diluent for tableting to relieve the delamination phenomenon between pellets and excipients during tablet pressing and reduce mechanical damage to the coating film. By examining the powder fluidity indexes such as angle of repose, bulk density, tapped density, and Hausner ratio of mixed particles, it was found that the flowability and compressibility are good and suitable for direct compression. Evaluate the basic properties of the sustained-release tablets, investigate the in vitro release behavior and study the release mechanism. The results of in vitro release test showed that the self-made sustained-release tablets could disintegrate into independent pellet units in phosphate buffer at pH 6.8 and release slowly within 24 h, which conformed to the first-order drug release model. The fluvoxamine maleate sustained-release pellet system tablets meet the requirements of preparation design and has a great commercial prospect.

Objective To explore the clinical significance of nucleolar antinuclear antibodies(ANA)in re-lated diseases.Methods This study was a retrospective study.Clinical samples of 71780 patients who visited the hospital from January 2017 to May 2022 were collected.Indirect immunofluorescence was used to detect ANA in clinical samples.Statistical analysis was conducted on the positivity rate of nucleolar ANA in clinical patients,as well as the relevant clinical information and laboratory characteristics of patients with autoimmune diseases(AID)with nucleolar ANA positivity.Results Among 71780 patients who underwent routine ANA testing,16778 were positive for ANA,with a positive rate of 23.37％.Among them,there were 1 708 cases of nucleolar type,accounting for 2.38％of all routine ANA tests,and the proportion of ANA positive cases was 10.18％.There was a statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the＞20-＜50 year old group and the ≥ 50 year old group(P＜0.05),while there was no statistically significant difference in the positive rate of nucleolar ANA between patients of different genders in the &le; 20 year old group(P＞0.05).There was a statistically significant difference in the positivity rate of nucleolar ANA among women of different age groups(P＜0.05),among them,the highest positive rate of nucleolar ANA was found in women aged between 20 and 50 years old.There was no statistically significant difference in the positive rate of nucleolar ANA among males of different age groups(P＞0.05).The positivi-ty rate of ANA was the highest among patients in the Department of Rheumatology and Immunology(70.35％),but nucleolar ANA positivity was mainly seen in departments such as Reproductive Medicine Cen-ter(12.90％),Respiratory Medicine(12.40％),and Neurology(11.29％),and the difference in positivity rates between departments was statistically significant(P＜0.05).Out of 1 708 nucleolar ANA positive indi-viduals,420 underwent ANA titers,including 34 AID patients and 386 non AID patients.There was no statis-tically significant difference in nucleolus positive titers between non AID patients and AID patients(P＞0.05).Conclusion The nucleolus type is a common fluorescence pattern in ANA positive individuals,and there are gender and age differences in ANA positive individuals.The positive rate and titer of nucleolar ANA vary among different AID diseases.Combined with other immune function indicators,and it is helpful for early differential diagnosis of AID.

Objective To explore the efficacy of early hyperbaric oxygen therapy(HBOT)combined with median nerve electrical stimulation(MNES)in the treatment of severe traumatic brain injury(sTBI)and its impact on hemodynamics,coma degree,and neurological function of patients.Methods A total of 78 patients with sTBI admitted to the General Hospital of Western Theater Command from March 2020 to October 2021 were selected as the research subjects.The patients were randomly divided into the control group and the observation group,with 39 patients in each group.The patients in both groups underwent basic treatments such as water,electrolyte and acid-base balance,nutritional support,anti-infection,and decompressive craniectomy.On this basis,patients in the control group received early HBOT,while patients in the observation group received both HBOT and MNES.Their clinical efficacy was compared between the two groups.Before and after treatment,dual-channel transcranial Doppler ultrasound was performed to detect hemodynamic indicators such as peak systolic blood flow velocity(Vs),mean blood flow velocity(Vm),and pulsatility index(PI)in the middle cerebral artery of patients in the two groups.The Glasgow Coma Scale(GCS)score was used to evaluate the degree of coma of patients in the two groups,the National Institutes of Health Stroke Scale(NIHSS)score was used to assess the neurological deficits of patients in the two groups,and the enzyme-linked immunosorbent assay was used to measure the levels of central nervous system specific protein(S100-β),glial fibrillary acidic protein(GFAP),and myelin basic protein(MBP).Complications during treatment of patients in the two groups were recorded,and their incidence was compared.Results The total effective rate of patients in the control and observation groups was 79.49％(31/39)and 92.31％(36/39),respectively.The total effective rate in the observation group was significantly higher than that in the control group(x2=8.971,P＜0.05).There was no significant difference in Vm,Vs,and PI between the two groups before treatment(P＞0.05).After treatment,the Vm and Vs in both groups were significantly higher than those before treatment,while the PI was significantly lower than that before treatment(P＜0.05);and the Vm and Vs in the observation group were signifi-cantly higher than that those in the control group,while the PI was significantly lower than that in the control group(P＜0.05).There was no significant difference in GCS and NIHSS scores between the two groups before treatment(P＞0.05).After treatment,the GCS score in both groups was significantly higher than that before treatment,while the NIHSS score was significantly lower than that before treatment(P＜0.05);and the GCS score in the observation group was significantly higher than that in the control group,while the NIHSS score was significantly lower than that in the control group(P＜0.05).There was no significant difference in S100-β,GFAP,and MBP levels between the two groups before treatment(P＞0.05).After treatment,the S100-β,GFAP,and MBP levels in both groups were significantly lower than those before treatment(P＜0.05),and the S100-β,GFAP,and MBP levels in the observation group were significantly lower than those in the control group(P＜0.05).During treatment,the incidence of complications in the control and observation groups was 23.08％(9/39)and 20.51％(8/39),respectively,showing no significant difference(x2=2.328,P＞0.05).Conclusion Early HBOT combined with MNES shows good efficacy in treating sTBI,which can effectively improve the patients'hemodynamic level,alleviate the severity of coma,enhance neurological function,and promote early recovery of consciousness,without increased risk of complications.

Attention deficit hyperactivity disorder （ADHD）， also known as hyperactivity disorder in children， is a behavioral disorder commonly found in children， particularly preschool-aged children. This disorder can lead to cognitive impairment， learning difficulties， conduct disorders， and other mental health issues， severely impacting the quality of life for affected children. Moreover， the global prevalence of ADHD continues to rise. Establishing an animal model that closely aligns with clinical symptoms and the pathogenesis of the disease is crucial for advancing research on the prevention and treatment of ADHD. In recent years， research on animal models of ADHD has rapidly developed. Researchers have developed nearly 20 animal models from genetic and environmental perspectives. However， most of these models are still in the exploratory stage， and there is insufficient research to thoroughly investigate their pathogenesis， core characteristics， and drug effects. The spontaneously hypertensive rat （SHR） is currently the most commonly used animal model for ADHD because of its excellent face validity and developmental stage that better corresponds to childhood. In addition， dopamine transporter （DAT） knockout mice， LPHN3 knockout rats， and neonatal rat hypoxia models have also shown good face validity. Some researchers have injected SHRs with daily doses of levothyroxine sodium， which not only induces typical ADHD symptoms in the rats but also exhibits signs of Yin deficiency and Yang hyperactivity， which successfully simulates the Yin deficiency and Yang hyperactivity syndrome type of ADHD， providing a new approach for constructing and evaluating ADHD animal models that combine both traditional Chinese and western medicine. This article reviewed ADHD animal models reported in China and abroad over the past decade， summarized rodent models of ADHD into three major categories： genetic models， chemically induced models， and environmentally induced models， and analyzed each category to provide a reference for selecting and exploring appropriate models for experimental ADHD research.

Objective: To compare the effectiveness of qualitative and quantitative fecal immunochemical tests (FIT) in identifying colorectal cancer, so as to provide insights into perfecting screening strategies for colorectal cancer. Methods: Participants in the Colorectal Cancer Screening Program for Key Populations in Zhejiang Province from May 2020 to December 2021 were recruited, and their demographic information, lifestyle and disease history were collected through a questionnaire survey. Qualitative or quantitative FIT along with a questionnaire-based risk assessment were employed as the initial screening tests. Individuals who were positive in any FIT or had high-risk assessment results were required to attend a subsequent colonoscopy examination. The positive rate, detection rate of colorectal cancer, positive predictive value and number of colonoscopies required were compared between qualitative and quantitative FITs, and stratified analyses by gender and age were conducted. Results: Totally 4 099 769 participants were included. The qualitative FIT group included 3 574 917 individuals, yielding a positive rate of 11.35%, a detection rate of 1.19%, a positive predictive value of 0.48% and 83.84 colonoscopies required to detect one cancer case. The quantitative FIT group involved 524 852 individuals, yielding a positive rate of 6.70%, a detection rate of 2.31%, a positive predictive value of 1.01% and 43.23 colonoscopies required to detect one cancer case. The quantitative FIT group showed significantly higher detection rate of colorectal cancer, higher positive predictive value and less number of colonoscopies required compared to the qualitative FIT group (all P<0.05). The same results were obtained after stratification by gender and age. Conclusion Compared to qualitative FIT, quantitative FIT improves the detection of colorectal cancer and reduces the workload of colonoscopy examinations, making it more suitable for colorectal cancer screening in large-scale populations.

Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Objective To investigate the expression of essential meiotic endonuclease 1(EME1)in liver cancer tissue and its effect on the biological behavior of hepatoma cells.Methods The TCGA database was used to identify the differentially expressed genes between liver cancer tissue and paracancerous tissue.Immunohistochemistry and Western Blot were used to measure the expression abundance of EME1 in liver cancer tissue.A lentivirus was constructed by short hairpin RNA,and BEL-7404 cells were transfected with the lentivirus to interfere with the expression of the EME1 gene;the cells were divided into silencing group(shEME1 group)and control group(shCtrl group).Quantitative real-time PCR and Western Blot were used to measure the mRNA and protein expression levels of EME1;Celigo Image Cytometer and MTT assay were used to measure cell proliferation rate;flow cytometry was used to observe cell cycle;Caspase 3/7 activity was used to measure cell apoptosis.The independent-samples t-test was used for comparison between two groups.Results TCGA results showed that the mRNA expression level of EME1 in liver cancer tissue was 18.9 times that in paracancerous tissue(t=5.00,P<0.001),and the protein expression level of EME1 in liver cancer tissue was 7.0 times(based on immunohistochemistry:8.4±2.6 vs 1.2±0.4,t=7.55,P<0.001)or 2.5 times(based on Western Blot:249.0%±35.5%vs 100.0%±77.8%,t=3.02,P<0.05)that in paracancerous tissue.After lentivirus infection,compared with the shCtrl group,the shEME1 group had an mRNA expression level of EME1 reduced by 29.9%(29.9%±0.9%vs 100.0%±3.6%,t=32.82,P<0.001),a protein expression level of EME1 reduced by 35.7%(35.7%±14.9%vs 100.0%±28.9%,t=3.42,P<0.05),and a level of cell counting reduced by 45.1%(4 053±167 vs 8 988±477,t=16.91,P<0.001),as well as a level of cell activity reduced to 66.9%(0.518±0.046 vs 0.774±0.022,t=8.74,P<0.001)and a level of colony forming ability reduced to 29.0%(75±6 vs 260±9,t=28.92,P<0.001).Compared with the shCtrl group,the shEME1 group had a significant increase in the proportion of cells in G1 phase(49.9%vs 44.0%,t=8.96,P<0.001)and significant reductions in the proportion of cells in G2/M phase(15.9%vs 17.9%,t=9.13,P<0.001)and S phase(34.2%vs 38.1%,t=6.91,P<0.001),while Caspase 3/7 activity was enhanced by 1.5 times(145.8%±5.9%vs 100.0%±2.3%,t=12.50,P<0.001).Conclusion EME1 is highly expressed in liver cancer tissue,and silencing the EME1 gene can inhibit the proliferation of hepatoma cells and promote cell apoptosis.

To explore the biological characteristics related to the pathogenesis and severity of respiratory syncytial virus (RSV) bronchiolitis by RNA sequencing of white blood cells in children with RSV bronchiolitis. This study is a case-control study. A total of 87 children diagnosed with bronchiolitis and RSV antigen positive and/or RSV nucleic acid positive in the pediatric respiratory department of the Second Affiliated Hospital of Wenzhou Medical University from October 2019 to April 2022 were selected as the case group. The case group was divided into three groups based on the condition: mild, moderate, and severe, and there were two groups according to the presence or absence of atopic symptoms: the atopic group and the non -atopic group, forty healthy children in the same period were selected as the control group. The whole blood leukocyte RNA of the children in the case group and the control group was extracted for RNA sequencing, and the data were analyzed to obtain differentially expressed genes (DEGs). Then, the immunobiological pathways and genes related to the pathogenesis, disease condition, and atopy were screened through Gene Ontology (GO) annotation, Kyoto Gene and Genome Encyclopedia (KEGG) annotation, and protein interaction network (PPI) construction methods. Construct the weighted gene co-expression network analysis (WGCNA) module to identify potential biological indicators related to disease severity.Compared with the control group, the case group had a total of 1 782 DEGs, including 1 586 upregulated genes and 196 downregulated genes. The GO pathway enrichment of DEGs is mainly enriched in molecular functions such as peroxidase activity and oxidoreductase activity. In the cytological components, it is mainly enriched in cytoplasmic vesicle lumen and secretory granule lumen. In biological processes, it is mainly enriched in processes such as neutrophil activation involved in immune responses, neutrophil degranulation, and neutrophil activation. KEGG analysis is mainly concentrated in the signal pathway of the viral protein interaction with cytokine and cytokine receptor. A PPI network was constructed to screen four genes at the core position, including CCL2, IL-10, MMP9 and JUN. The DEGs obtained by comparing different disease groups with the control group are mainly enriched in retrograde endocannabinoid signaling and cell apoptosis pathways. WGCNA analysis showed that the brown module related to oxygen saturation was most closely related to the disease, and its gene was mainly enriched in the RNA helicase retinoic acid inducible gene-I (RIG-I) like receptor signal pathway. There are 230 specific DEGs in the atopic group and 444 in the non -atopic group. KEGG enrichment analysis results show that both groups are enriched to NF-κB signaling pathway, the characteristic does not cause significant changes in immune response and transcriptome characteristics in children with RSV bronchiolitis. In conclusion, neutrophil activation, degranulation pathway and signal pathway of interaction between viral protein and cytokine and cytokine receptor are involved in the immune response of RSV bronchiolitis host. CCL2, IL-10, MMP9 and JUN genes may be associated with the pathogenesis. They might be potential biomarkers related to disease severity in RIG-I like receptors, cell apoptosis, and endogenous cannabinoid related signaling pathways.