Hemorrhoids are common anorectal diseases with complex pathogenesis, and there is still a lack of ideal experimental animal models for research on their prevention and treatment. In this paper, Chinese and English databases are searched with the keywords "hemorrhoids" and "animal model", and 36 relevant studies are finally included. The shortcomings of existing hemorrhoid animal models in integrating the clinical disease and syndrome characteristics of traditional Chinese and Western medicine are systematically analyzed, and the consistency of various models with clinical practice is evaluated. The studies are divided into four categories according to modeling methods: chemical modeling, physical modeling, biological modeling, and combined modeling. The clinical consistency of modeling is evaluated in combination with the diagnostic points of hemorrhoids in traditional Chinese and Western medicine. The results show that there are significant differences in the reproduction of clinical indicators by different modeling methods. According to clinical consistency, the models can be divided into three grades: high-consistency models are mainly based on combined modeling methods (such as induction by carrageenan combined with norepinephrine hydrochloride), which can more comprehensively simulate core pathological changes such as venous congestion and local inflammation; moderate-consistency models adopt single chemical or physical intervention (such as local inflammation induced by croton oil or vein ligation), which can only reproduce part of the pathological process; low-consistency models mostly adopt direct stimulation, with limited research value for pathological characteristics. Existing animal models have obvious advantages in replicating Western medical structural lesions of hemorrhoids, but they still have obvious defects in simulating the chronic disease course and stably reproducing the characteristics of traditional Chinese medicine syndromes, and a unified standard has not yet been formed for the traditional Chinese medicine evaluation system of models. In conclusion, it is still necessary to further explore the construction of high-quality integrated disease and syndrome animal models for hemorrhoids in traditional Chinese and Western medicine. Future research should integrate the theories of traditional Chinese and Western medicine, adopt multi-factor chronic modeling strategies, and establish a standardized comprehensive evaluation system covering macroscopic signs and microscopic indicators. This paper provides a reference for constructing standardized integrated disease and syndrome animal models of hemorrhoids that conform to the pathological changes of Western medicine and take into account the characteristics of traditional Chinese medicine syndromes, with the aim of providing more effective experimental tools for research on the pathogenesis of hemorrhoids and their integrated prevention and treatment with traditional Chinese and Western medicine.

Objective To develop an erythrocyte-based delivery system for butyrylcholinesterase(BChE)that is capable of prophylaxis against organophosphorus nerve agents.Methods Recombinant BChE was produced and analyzed for oligomerization via polyacrylamide gel electrophoresis(PAGE)and Western blotting.A modified hypotonic preswelling method was employed to prepare BChE-loaded erythrocytes.The drug loading capacity and encapsulation efficiency were quantified using enzyme-linked immunosorbent assay(ELISA).Catalytic activity was assessed in vitro with an activity detection kit.The system was characterized via scanning electron microscopy(SEM),flow cytometry and a hematology analyzer.Results Recombinant BChE predominantly existed as dimers(85％dimer,15％monomer).The optimized volume ratio of erythrocytes to hypotonic solution was determined as 1:7.Compared with native and empty erythrocytes,BChE-loaded erythrocytes exhibited significantly higher catalytic activity(P＜0.001).The mean corpuscular volume of BChE-loaded erythrocytes increased(P＜0.001),while the mean content of corpuscular hemoglobin and hemoglobin in erythrocytes per 100 mL decreased(P＜0.001).SEM revealed no morphological differences(biconcave disc shape).Hypotonic preswelling moderately increased erythrocyte apoptosis(P＜0.001),but no statistical difference was observed between BChE-loaded and hypotonic-treated erythrocytes(P＞0.05).CD47 expression remained unchanged compared to native erythrocytes(P＞0.05).Conclusion The modified hypotonic preswelling method can generate BChE-loaded erythrocytes that retain the characteristics of native erythrocytes while conferring catalytic activity,offering a novel strategy for clinical intervention against organophosphorus poisoning.

Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.

Objective:To investigate the clinical subtypes of acute aortic dissection (AAD) through latent class analysis.Methods:This study was a multicenter retrospective cohort study. Patients with AAD admitted to five hospitals, including Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Henan Provincial People′s Hospital, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, between August 2010 and December 2021 were enrolled. Based on clinical and biological characteristics, latent class analysis (models with 2 to 5 latent classes) was conducted to classify the enrolled patients. The optimal classification scheme was determined using model fitting evaluations, including log-likelihood (LL), entropy, Lo-Mendell-Rubin adjusted likelihood ratio test and so on. Clinical data of different subtypes were compared, and in-hospital mortality was analyzed across the entire population and among subgroups receiving different treatments.Results:A total of 2 689 AAD patients, aged 54 (46, 63) years were included, with 1 305 (48.5%) having DeBakey type Ⅰ, 156 (5.8%) type Ⅱ, and 1 228 (45. 7%) type Ⅲ dissections. The cohort comprised 2 134 (79.4%) males. The overall in-hospital mortality rate was 22.8% (613/2 689). Latent class analysis indicated that a two-class model was optimal (LL=147 413.242, entropy=0.812, and PLMRT<0.001). Patients were classified into two subtypes, named clinical subtype 1 and clinical subtype 2. Compared to clinical subtype 1, clinical subtype 2 had a higher proportion of females, was older, had more dissections involving the ascending aorta, and exhibited higher rates of organ dysfunction (elevated alanine aminotransferase and creatinine levels) and inflammatory response (neutrophilia) (all P<0.05). Clinical subtype 2 also showed higher in-hospital mortality compared to subtype 1 (26.3% (238/905) vs. 21.0% (375/1 784), P=0.002). Among patients undergoing surgical treatment, clinical subtype 2 had higher mortality than subtype 1 (40.1% (67/167) vs. 30.0% (101/337), P=0.027). However, no significant differences in mortality were observed between the two subtypes among patients receiving medical therapy or endovascular and hybrid procedures (all P>0.05). Conclusions:Comprehensive latent class analysis identifies two subtypes of AAD with distinct clinical characteristics and treatment responses. These findings provide new insights into individualized clinical decision-making and prognostic evaluation for AAD patients.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective To investigate the expression of N-acetyltransferase 10(NAT10),serine hydroxymethyltransferase 2(SHMT2)and YTH domain family protein 1(YTHDF1)in lung cancer tissues and their correlation with clinicopathological characteristics and prognosis.Methods A total of 98 lung cancer patients admitted to our hospital from April 2020 to April 2021 were regarded as the observation subjects.The cancerous tissues and adjacent tissues of the patient during surgery were collected.Immunohistochemistry was used to detect the expression levels of NAT10,SHMT2 and YTHDF1.The patients were followed up for 3 years and divided into the survival group and the death group according to their prognosis.The data of general clinicopathological characteristics were collected and analyzed.The relationship between NAT10,SHMT2 and YTHDF1 with the prognosis of patients were analyzed.Multivariate Cox regression was used to analyze the influencing factors of lung cancer patients.Results The high expression ratios of NAT10,SHMT2 and YTHDF1 in cancer tissues were obviously higher than those in adjacent tissues(P＜0.05).The expression of NAT10 and YTHDF1 was related to clinical stage,degree of differentiation and lymph node metastasis(P＜0.05),and the expression of SHMT2 was correlated with clinical stage,degree of differentiation,tumor diameter,and lymph node metastasis(P＜0.05).There were statistically significant differences in tumor diameter,clinical stage,degree of differentiation,lymph node metastasis,and expressions of NAT10,SHMT2,and YTHDF1 between the survival group and the death group(P＜0.05).NAT10,SHMT2,YTHDF1 patient survival rates significantly below the low of high expression patients(x2=6.354,P=0.012,x2=8.512,P=0.004,x2=4.791,P=0.029).Lymph node metastasis,high expression of NAT10,SHMT2 and YTHDF1 are all risk factors affecting the prognosis of patients(P＜0.05).Conclusion NAT10,SHMT2,and YTHDF1 are all highly expressed in the tissues of lung cancer,and have a certain correlation with clinical pathological characteristics and prognosis.They may serve as relevant evaluation indicators for the prognosis of lung cancer patients.

Objective To investigate the anti-inflammatory protective effects of remimazolam on microglial cells and elucidates the potential molecular mechanisms underlying these effects. Methods The mouse microglial cell line (BV2) was selected as the research object. The following groups were set up:the control group (complete medium),the Rema group (200 μg/mL remimazolam),the model group (1 μg/mL lipopolysaccharide,LPS),and different-concentration administration groups (1 μg/mL LPS+50,100,200 μg/mL remimazolam). In the Rema group,cells were treated with 200 μg/mL remimazolam alone for 26 h. In the model group,cells were treated with LPS for 24 h. In the different-concentration administration groups,cells were pre-treated with different concentrations of remimazolam for 2 h,and then treated with LPS for 24 h. The effects of LPS and remimazolam on the morphology of BV2 cells were observed and evaluated using an optical microscope. Cell viability was determined using the CCK-8 assay,while the expression and secretion of inflammatory cytokines were quantified by quantitative real-time PCR and ELISA. Reactive oxygen species (ROS) levels were measured using a fluorescent probe. Additionally,malondial-dehyde (MDA) content,superoxide dismutase (SOD) activity,and glutathione peroxidase (GSH) activity were evaluated using respective assay kits. Western blot analysis was conducted to examine the protein expression levels of Bax,Bcl-2,IL-1β,RAGE,NF-κB,p-NF-κB,IκBα,p-IκBα,iNOS,and Arg-1. Immunofluorescence staining was employed to visualize NF-κB nuclear translocation and M1/M2 polarization in the cells. Results Compared to the control group,LPS-treated BV2 cells demonstrated significantly reduced cell viability,elevated expression and se-cretion of inflammatory cytokines (TNF-α,IL-6,IL-1β),decreased activities of SOD and GSH,and increased in-tracellular levels of MDA and ROS. Additionally,RAGE protein levels were upregulated,along with enhanced phos-phorylation of IκBα and NF-κB,leading to observable NF-κB nuclear translocation. The expression of the M1 marker iNOS was upregulated,while that of the M2 marker Arg-1 was downregulated. In contrast,in the LPS+Rema group,cell viability was restored,expression and secretion of inflammatory cytokines were attenuated,SOD and GSH activities were improved,and levels of MDA and ROS were reduced compared to the LPS group. Furthermore,RAGE protein expression and phosphorylation levels of IκBα and NF-κB were diminished,inhibiting NF-κB nuclear translocation. The expression of the M1 marker iNOS was downregulated,while that of the M2 marker Arg-1 was up-regulated. Conclusion Remimazolam mitigates LPS-induced inflammation by facilitating the transition of microglial cells from the M1 to the M2 phenotype via modulation of the NF-κB pathway and reduction of ROS production.

Objective To investigate the expression of N-acetyltransferase 10(NAT10),serine hydroxymethyltransferase 2(SHMT2)and YTH domain family protein 1(YTHDF1)in lung cancer tissues and their correlation with clinicopathological characteristics and prognosis.Methods A total of 98 lung cancer patients admitted to our hospital from April 2020 to April 2021 were regarded as the observation subjects.The cancerous tissues and adjacent tissues of the patient during surgery were collected.Immunohistochemistry was used to detect the expression levels of NAT10,SHMT2 and YTHDF1.The patients were followed up for 3 years and divided into the survival group and the death group according to their prognosis.The data of general clinicopathological characteristics were collected and analyzed.The relationship between NAT10,SHMT2 and YTHDF1 with the prognosis of patients were analyzed.Multivariate Cox regression was used to analyze the influencing factors of lung cancer patients.Results The high expression ratios of NAT10,SHMT2 and YTHDF1 in cancer tissues were obviously higher than those in adjacent tissues(P＜0.05).The expression of NAT10 and YTHDF1 was related to clinical stage,degree of differentiation and lymph node metastasis(P＜0.05),and the expression of SHMT2 was correlated with clinical stage,degree of differentiation,tumor diameter,and lymph node metastasis(P＜0.05).There were statistically significant differences in tumor diameter,clinical stage,degree of differentiation,lymph node metastasis,and expressions of NAT10,SHMT2,and YTHDF1 between the survival group and the death group(P＜0.05).NAT10,SHMT2,YTHDF1 patient survival rates significantly below the low of high expression patients(x2=6.354,P=0.012,x2=8.512,P=0.004,x2=4.791,P=0.029).Lymph node metastasis,high expression of NAT10,SHMT2 and YTHDF1 are all risk factors affecting the prognosis of patients(P＜0.05).Conclusion NAT10,SHMT2,and YTHDF1 are all highly expressed in the tissues of lung cancer,and have a certain correlation with clinical pathological characteristics and prognosis.They may serve as relevant evaluation indicators for the prognosis of lung cancer patients.

Objective:To evaluate the epidemiological characteristics and influencing factors of out-of-hospital sudden cardiac death (SCD) in Hangzhou from 2016 to 2019.Methods:SCD events recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019 were reviewed. Demographic and mortality data were recorded, and the distribution patterns of SCD events in terms of date, time, and population with different characteristics were observed. Time series analysis method and a distributed lag nonlinear model based on quasi-Poisson distribution were used to explore the possible nonlinear association between ambient temperature and SCD incidence.Results:A total of 4 744 out-of-hospital sudden death events were recorded by Hangzhou Emergency Center from January 1, 2016 to December 31, 2019. After excluding non-SCD events and observed events with missing items, 3 743 SCD events were finally included in the study. The survey results showed that the incidence of out-of-hospital SCD in Hangzhou was 96.5 cases per 100 000 person-years. Most of the people who experienced SCD were aged ≥60 years. The incidence in males (2 462 cases, 66%) was significantly higher than that in females (1 281 cases, 34%), and the proportion of events occurring during the day (2 737 cases, 73%) was significantly higher than that at night (1 006 cases, 27%), mainly occurring between 7: 00 and 9: 00. High temperature was associated with an increased risk of SCD. When the average daily temperature was higher than 25.5 ℃, the risk of SCD increased with the further increase of average daily temperature.Conclusions:SCD events mainly occur in the elderly population aged ≥60 years, with a significantly higher incidence in males than in females, and more frequently during the day than at night, mainly between 7: 00 and 9: 00 in the morning. High temperature is closely related to the risk of SCD. It is particularly important to carry out targeted SCD screening and prevention for different populations and implement appropriate prevention strategies for high-risk groups of SCD in high-temperature weather.

Objective:To investigate the clinical subtypes of acute aortic dissection (AAD) through latent class analysis.Methods:This study was a multicenter retrospective cohort study. Patients with AAD admitted to five hospitals, including Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Henan Provincial People′s Hospital, Central China Fuwai Hospital of Zhengzhou University (Fuwai Central China Cardiovascular Hospital), the Third Affiliated Hospital of Xinxiang Medical University and the Second Affiliated Hospital of Chongqing Medical University, between August 2010 and December 2021 were enrolled. Based on clinical and biological characteristics, latent class analysis (models with 2 to 5 latent classes) was conducted to classify the enrolled patients. The optimal classification scheme was determined using model fitting evaluations, including log-likelihood (LL), entropy, Lo-Mendell-Rubin adjusted likelihood ratio test and so on. Clinical data of different subtypes were compared, and in-hospital mortality was analyzed across the entire population and among subgroups receiving different treatments.Results:A total of 2 689 AAD patients, aged 54 (46, 63) years were included, with 1 305 (48.5%) having DeBakey type Ⅰ, 156 (5.8%) type Ⅱ, and 1 228 (45. 7%) type Ⅲ dissections. The cohort comprised 2 134 (79.4%) males. The overall in-hospital mortality rate was 22.8% (613/2 689). Latent class analysis indicated that a two-class model was optimal (LL=147 413.242, entropy=0.812, and PLMRT<0.001). Patients were classified into two subtypes, named clinical subtype 1 and clinical subtype 2. Compared to clinical subtype 1, clinical subtype 2 had a higher proportion of females, was older, had more dissections involving the ascending aorta, and exhibited higher rates of organ dysfunction (elevated alanine aminotransferase and creatinine levels) and inflammatory response (neutrophilia) (all P<0.05). Clinical subtype 2 also showed higher in-hospital mortality compared to subtype 1 (26.3% (238/905) vs. 21.0% (375/1 784), P=0.002). Among patients undergoing surgical treatment, clinical subtype 2 had higher mortality than subtype 1 (40.1% (67/167) vs. 30.0% (101/337), P=0.027). However, no significant differences in mortality were observed between the two subtypes among patients receiving medical therapy or endovascular and hybrid procedures (all P>0.05). Conclusions:Comprehensive latent class analysis identifies two subtypes of AAD with distinct clinical characteristics and treatment responses. These findings provide new insights into individualized clinical decision-making and prognostic evaluation for AAD patients.