Objective: To investigate the distribution characteristics of ABO and Rh blood group antigen phenotypes among blood donors in the Yantai, Shandong. Methods: Blood samples from 310 180 voluntary blood donors in Yantai collected from January 2019 to December 2023 were tested for ABO and Rh blood group antigens using standard serological methods. RhD-negative samples were further typed for C, c, E, and e antigens. Population genetic analysis of blood groups was performed: allele frequencies were inferred from ABO phenotypes, and Rh allele/haplotype frequencies were estimated based on the proportion of RhD-negative donors and CcEe antigen typing, followed by Hardy-Weinberg equilibrium testing. Results: The phenotypic distribution frequency of ABO blood groups was B(32.72%)>O(28.93%)>A(27.65%)>AB(10.70%). The inferred allele frequencies were r(53.74%)>q(24.78%)>p(21.48%), consistent with Hardy-Weinberg equilibrium (P>0.05). A total of 1 872 Rh-negative donors (0.603%) were identified. The most common Rh phenotypes were ccdee (59.56%) and Ccdee (30.18%). The distribution of Rh antigen phenotypes deviated significantly from Hardy-Weinberg equilibrium (χ =37.15, P<0.001), with the cde haplotype showing the highest frequency. There was no statistically significant difference in ABO blood group distribution between RhD-positive and RhD-negative donors (P>0.05). Conclusion: The ABO blood group distribution among voluntary blood donors in Yantai is generally stable and consistent with population genetic equilibrium, whereas the Rh antigen phenotype distribution deviates from equilibrium, indicating potential underlying genetic structural differences.

Objective To investigate the efficacy and safety of domestic RECO flow restoration device in endovascular treatment of acute ischemic stroke(AIS)patients in a real-world setting.Methods From January 2019 to June 2021,consecutive patients with acute intracranial vessel occlusion treated with RECO device from 8 stroke centers in Jiangsu Province were analyzed retrospectively.Baseline and clinical data were collected,including age,gender,baseline modified Rankin scale(mRS)scores,National Institutes of Health stroke scale(NIHSS)score on admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,responsible location of occlusion,wake-up stroke,and medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary heart disease,peripheral arterial disease),smoking,and alcohol consumption.Furthermore,surgical parameters were collected,including time indicators(intervals between symptom onset,admission,puncture and recanalization),preoperative intravenous thrombolysis,general anesthesia,combination of aspiration,number of passes,first pass effect(modified thrombolysis in cerebral infarction[mTICI]grade 3 achieved with s single stent-based thrombectomy),rescue therapy(including thrombectomy with other stents,intra-arterial urokinase thrombolysis,intra-arterial application of tirofiban,emergency angioplasty[stent implantation,balloon dilatation,balloon dilatation combined with stent implantation]),balloon guided catheter and NIHSS score at discharge.The effectiveness indicators included immediate successful recanalization after the operation(mTICI grade ≥ 2b),complete recanalization(mTICI grade 3),and a good prognosis at 90 d after the operation(mRS score ≤2).The safety indicators included symptomatic intracranial hemorrhage(sICH)within 24 h after the operation,device-related intraoperative complications(such as thrombus escape,iatrogenic dissection,bleeding at the surgical site),and all-cause mortality within 90 days after the operation.All patients were divided into the anterior circulation occlusion group and the posterior circulation occlusion group according to the location of the responsible occluded vessel,and the effectiveness and safety indexes were analyzed.Results A total of 366 patients with AIS caused by intracranial vessel occlusion who underwent mechanical thrombectomy with the domestic RECO thrombectomy stent were included.The average age was(69±11)years,with 54 patients(14.8％)over 80 years old and 221 patients(60.4％)male.There were 296 patients in the anterior circulation occlusion group and 70 patients in the posterior circulation occlusion group.(1)Immediate successful recanalization(mTICI grade≥2b)was achieved in 337 patients(92.1％),and complete recanalization was achieved in 282 patients(77.0％)immediately after the operation.The average number of thrombectomies was(1.9±1.0)times,and 141 patients(38.5％)achieved recanalization on the first attempt.9 patients(2.5％)used other stents during the operation,and 65 patients(17.8％)underwent emergency angioplasty.The incidence of sICH within 24 h after the operation was 10.9％(40/366),the good prognosis rate at 90 d after the operation was 53.6％(196/366),and the all-cause mortality rate at 90 d after the operation was 23.0％(84/366).The incidence of device-related intraoperative complications was 3.6％(13/366).The median time from arterial puncture to recanalization was 75(52,110)min,and the median time from onset to recanalization was 370(280,488)min.(2)The good prognosis rates at 90 d after the operation in the anterior and posterior circulation occlusion groups were 55.1％(163/296)and 47.1％(33/70),respectively.The immediate successful recanalization rates were 93.2％(276/296)and 87.1％(61/70),respectively.The immediate complete recanalization rates were 79.1％(234/296)and 68.6％(48/70),respectively.The incidence of sICH within 24h after the operation was 12.2％(36/296)and 5.7％(4/70),respectively.The incidence of device-related intraoperative complications was 3.7％(11/296)and 2.9％(2/70),respectively.The all-cause mortality rate within 90 d after the operation was 21.6％(64/296)and 28.6％(20/70),respectively.There were no statistically significant differences between the two groups in the above aspects(all P＞0.05).Conclusions The application of the domestic RECO thrombectomy stent in the treatment of AIS caused by intracranial vessel occlusion can effectively and safely achieve vascular recanalization.The results of this study still need to be further verified by prospective controlled studies.

Objective To establish a model of indirectly induced respiratory tract infection with influenza A subtypes H1N1 and H3N2 in animals,to screen influenza virus hosts,and to provide theoretical support for the clinical control of influenza viruses.Methods Fifty BALB/c mice and 50 Hartley guinea pigs were randomly divided into five groups(10 animals/group for each species):normal control group,virus infects 1 group,virus infects 2 group,close transmission 1 group,and close transmission 2 group.Mice and guinea pigs in virus infects 1 and 2 groups were administered influenza A(H1N1)and influenza A(H3N2)viruses via nasal drip.For both virus infects 1 and 2 groups,animals were housed together with those in the close transmission group at a 1∶1 ratio on the following day.On day 7,the lung function,viral titer and viral load of the nasal tissue,trachea,and lung tissue of each group were measured,and pathological changes of the trachea and lung tissue of animals in the close transmission group were evaluated.Results In mice,the viral titers and viral loads of nasal,tracheal,and lung tissues of virus infects 1 and 2 and the closely transmitted groups 1 and 2 were significantly higher(P＜0.01),pathological scores of the trachea and lung tissues were significantly higher(P＜0.01),and the FVC and FEV20 of virus infects l and 2 groups were significantly lower(P＜0.01)than those in the normal control group.The nasal tissue,trachea and lung tissues of guinea pigs in virus infects 1 and 2 groups and close transmission groups 1 and 2 showed significantly higher viral titers and viral loads(P＜0.01),significantly higher trachea and lung histopathological scores(P＜0.01),and significantly lower FVC and FEV200(P＜0.01)than those of the normal control group.Conclusions In this study,influenza A subtypes H1N1 and H3N2 were used to indirectly induce respiratory tract infections in mice and guinea pigs for analyses of animal lung function,respiratory viral titers,viral load,and pathology.The animal models of the indirect transmission of influenza viruses in the respiratory tract had certain limitations;for example,influenza viruses were transmitted less efficiently among mice than among guinea pigs.The guinea pig model was stable.These findings confirm that guinea pigs are suitable hosts for efficient virus replication and transmission.

Objective To establish a model of indirectly induced respiratory tract infection with influenza A subtypes H1N1 and H3N2 in animals,to screen influenza virus hosts,and to provide theoretical support for the clinical control of influenza viruses.Methods Fifty BALB/c mice and 50 Hartley guinea pigs were randomly divided into five groups(10 animals/group for each species):normal control group,virus infects 1 group,virus infects 2 group,close transmission 1 group,and close transmission 2 group.Mice and guinea pigs in virus infects 1 and 2 groups were administered influenza A(H1N1)and influenza A(H3N2)viruses via nasal drip.For both virus infects 1 and 2 groups,animals were housed together with those in the close transmission group at a 1∶1 ratio on the following day.On day 7,the lung function,viral titer and viral load of the nasal tissue,trachea,and lung tissue of each group were measured,and pathological changes of the trachea and lung tissue of animals in the close transmission group were evaluated.Results In mice,the viral titers and viral loads of nasal,tracheal,and lung tissues of virus infects 1 and 2 and the closely transmitted groups 1 and 2 were significantly higher(P＜0.01),pathological scores of the trachea and lung tissues were significantly higher(P＜0.01),and the FVC and FEV20 of virus infects l and 2 groups were significantly lower(P＜0.01)than those in the normal control group.The nasal tissue,trachea and lung tissues of guinea pigs in virus infects 1 and 2 groups and close transmission groups 1 and 2 showed significantly higher viral titers and viral loads(P＜0.01),significantly higher trachea and lung histopathological scores(P＜0.01),and significantly lower FVC and FEV200(P＜0.01)than those of the normal control group.Conclusions In this study,influenza A subtypes H1N1 and H3N2 were used to indirectly induce respiratory tract infections in mice and guinea pigs for analyses of animal lung function,respiratory viral titers,viral load,and pathology.The animal models of the indirect transmission of influenza viruses in the respiratory tract had certain limitations;for example,influenza viruses were transmitted less efficiently among mice than among guinea pigs.The guinea pig model was stable.These findings confirm that guinea pigs are suitable hosts for efficient virus replication and transmission.

Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Objective:To establish ultra-performance liquid chromatography (UPLC) fingerprint chromatograms for Erigeron breviscapu from different origins and storage conditions; To identify the Erigeron breviscapus from different habitats by chemometric analysis.Methods:Acquity UPLC HSS T3 (2.1 mm×100 mm,1.8 μm) chromatography column was used; mobile phase was 0.1% formic acid aqueous solution-acetonitrile; detection wavelength was 268 nm; flow rate was 0.25 ml/min; column temperature was 35 ℃; injection volume was 2 μl gradient elution. The UPLC fingerprint of Erigeron breviscapu from different origins was established. Similarity evaluation combined with chemometric analysis methods such as clustering analysis (CA), principal component analysis (PCA), orthogonal partial least squares method - discriminant analysis (OPLS-DA) were used to identify the origin of Breviscapine from different places. Fingerprint technology was used to evaluate the similarity of storage conditions for Erigeron breviscapu.Results:The UPLC fingerprint method met the methodological requirements. 30 batches of Erigeron breviscapus had 24 common peaks, and the similarity between Xingyi in Guizhou and Huize in Qujing was 0.702-0.783, while the similarity between Honghe Luli, Kunming Fuming and Dali was 0.861-0.970. All samples were divided into two categories according to their origin by CA: category Ⅰ: Xingyi in Guizhou and Huize in Qujing, and category Ⅱ: Dali, Kunming Fuming and Honghe Luli. The results of PCA were consistent with CA. OPLS-DA screened out 10 differential markers of Erigeron breviscapus from different habitats. Moreover, a total of 40 common peaks were identified in six batches of Erigeron breviscapus samples stored under different conditions. Based on the similarity analysis, Erigeron breviscapus samples stored at 30% humidity and 70% humidity were classified into two separate categories.Conclusions:The fingerprint method constructed in this study is stable and reliable, and the predictive ability and reliability of the OPLS-DA model are excellent. By combining the two methods, a clear division can be made between Erigeron breviscapus from Yunnan and Guizhou. Humidity conditions are an important factor in storing Erigeron breviscapus.

Objective:To explore the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia using network pharmacology; To verify the mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia through animal experiments.Methods:The active components and potential targets of Shiwei Chaihu Shugan Powder were searched in TCMSP and Uniprot databases. Breast hyperplasia genes were searched in GeneCards and OMIM databases. The intersection targets were obtained by online tool Venny, and the "drug-component-target" network was constructed by Cytoscape 3.8.2 software. The protein interaction (PPI) network was constructed using the String platform, and GO function and KEGG pathway enrichment analysis were performed using the DAVID annotation database. Molecular docking was performed using PDB, PubChem database, PyMOL 2.1 and AutoDockvina 1.2.5 software to predict the biological mechanism of Shiwei Chaihu Shugan Powder in the treatment of breast hyperplasia. Rats were divided into blank group, model group, tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups according to the random number table method, with 6 rats in each group. Except for the blank group, the other groups were prepared with the modified estrogen-progesterone-induced rat mammary hyperplasia model. Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups were intragastrically administered with Shiwei Chaihu Shugan Powder solution at 7.425 g/kg, 14.850 g/kg, and 29.700 g/kg respectively, while the tamoxifen group was intragastrically administered with 2.1 mg/kg tamoxifen. The blank group and the model group were intragastrically administered with the same volume of drinking water, once a day, for consecutive 28 d. The thickness of the mammary gland was measured by small animal ultrasound. The height and width of the nipples were measured by vernier calipers. The levels of serum E2 and P were detected by ELISA. The morphology of mammary tissue was observed by HE staining. The expressions of ERα, ERβ, SRC-1 and CBP/p300 proteins were detected by Western blot.Results:A total of 92 active components and 274 disease-drug intersection targets were screened out. GO functional enrichment analysis showed that Shiwei Chaihu Shugan Powder was closely related to positive regulation of gene expression, positive regulation of RNA polymerase Ⅱ promoter transcription, signal transduction, negative regulation of apoptosis process, response to heterogeneous stimulation, and regulation of hormone levels. KEGG enrichment analysis showed that the core targets might be related to NF-κB signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, PI3K/Akt signaling pathway, and regulating hormone levels. Molecular docking results showed that the core components had a good binding energy with the core target and a stable conformation. Compared with the model group, the thickness of the mammary gland in the tamoxifen group and Shiwei Chaihu Shugan Powder low-, medium- and high-dosage groups decreased ( P<0.01), the serum P level increased ( P<0.05), the expressions of ERα, SRC-1, and CBP/p300 proteins decreased ( P<0.01), and the expression of ERβ protein increased ( P<0.01); the height of the nipples in the Shiwei Chaihu Shugan Powder medium- and high-dosage groups and the tamoxifen group decreased ( P<0.01), and the serum E2 level increased ( P<0.05). Conclusion:Shiwei Chaihu Shugan Powder may play a role in the treatment of breast hyperplasia by regulating the levels of estrogen and related proteins.

Objective To investigate the efficacy and safety of domestic RECO flow restoration device in endovascular treatment of acute ischemic stroke(AIS)patients in a real-world setting.Methods From January 2019 to June 2021,consecutive patients with acute intracranial vessel occlusion treated with RECO device from 8 stroke centers in Jiangsu Province were analyzed retrospectively.Baseline and clinical data were collected,including age,gender,baseline modified Rankin scale(mRS)scores,National Institutes of Health stroke scale(NIHSS)score on admission,trial of Org 10172 in acute stroke treatment(TOAST)classification,responsible location of occlusion,wake-up stroke,and medical history(hypertension,diabetes mellitus,hyperlipidemia,atrial fibrillation,coronary heart disease,peripheral arterial disease),smoking,and alcohol consumption.Furthermore,surgical parameters were collected,including time indicators(intervals between symptom onset,admission,puncture and recanalization),preoperative intravenous thrombolysis,general anesthesia,combination of aspiration,number of passes,first pass effect(modified thrombolysis in cerebral infarction[mTICI]grade 3 achieved with s single stent-based thrombectomy),rescue therapy(including thrombectomy with other stents,intra-arterial urokinase thrombolysis,intra-arterial application of tirofiban,emergency angioplasty[stent implantation,balloon dilatation,balloon dilatation combined with stent implantation]),balloon guided catheter and NIHSS score at discharge.The effectiveness indicators included immediate successful recanalization after the operation(mTICI grade ≥ 2b),complete recanalization(mTICI grade 3),and a good prognosis at 90 d after the operation(mRS score ≤2).The safety indicators included symptomatic intracranial hemorrhage(sICH)within 24 h after the operation,device-related intraoperative complications(such as thrombus escape,iatrogenic dissection,bleeding at the surgical site),and all-cause mortality within 90 days after the operation.All patients were divided into the anterior circulation occlusion group and the posterior circulation occlusion group according to the location of the responsible occluded vessel,and the effectiveness and safety indexes were analyzed.Results A total of 366 patients with AIS caused by intracranial vessel occlusion who underwent mechanical thrombectomy with the domestic RECO thrombectomy stent were included.The average age was(69±11)years,with 54 patients(14.8％)over 80 years old and 221 patients(60.4％)male.There were 296 patients in the anterior circulation occlusion group and 70 patients in the posterior circulation occlusion group.(1)Immediate successful recanalization(mTICI grade≥2b)was achieved in 337 patients(92.1％),and complete recanalization was achieved in 282 patients(77.0％)immediately after the operation.The average number of thrombectomies was(1.9±1.0)times,and 141 patients(38.5％)achieved recanalization on the first attempt.9 patients(2.5％)used other stents during the operation,and 65 patients(17.8％)underwent emergency angioplasty.The incidence of sICH within 24 h after the operation was 10.9％(40/366),the good prognosis rate at 90 d after the operation was 53.6％(196/366),and the all-cause mortality rate at 90 d after the operation was 23.0％(84/366).The incidence of device-related intraoperative complications was 3.6％(13/366).The median time from arterial puncture to recanalization was 75(52,110)min,and the median time from onset to recanalization was 370(280,488)min.(2)The good prognosis rates at 90 d after the operation in the anterior and posterior circulation occlusion groups were 55.1％(163/296)and 47.1％(33/70),respectively.The immediate successful recanalization rates were 93.2％(276/296)and 87.1％(61/70),respectively.The immediate complete recanalization rates were 79.1％(234/296)and 68.6％(48/70),respectively.The incidence of sICH within 24h after the operation was 12.2％(36/296)and 5.7％(4/70),respectively.The incidence of device-related intraoperative complications was 3.7％(11/296)and 2.9％(2/70),respectively.The all-cause mortality rate within 90 d after the operation was 21.6％(64/296)and 28.6％(20/70),respectively.There were no statistically significant differences between the two groups in the above aspects(all P＞0.05).Conclusions The application of the domestic RECO thrombectomy stent in the treatment of AIS caused by intracranial vessel occlusion can effectively and safely achieve vascular recanalization.The results of this study still need to be further verified by prospective controlled studies.

Objective:To compare the clinical characteristics of patients with drug-induced liver injury (DILI) caused by Polygonum multiflorum and other drug-induced liver injuries (DILI).Methods:A retrospective cohort study was conducted. Clinical data of seventy-three cases confirmedly diagnosed with DILI caused by Polygonum multiflorum, 168 cases diagnosed with DILI caused by other traditional Chinese medicines, and 225 cases diagnosed with DILI caused by modern medicines admitted to Peking University First Hospital, the Fipth People's Hospital of Wuxi, Yantai Qishan Hospital, and Qinhuangdao Third Hospital from January 1995 to August 2019 were selected and collected as the research subjects. The Mann-Whitney U test was used for comparison of skewed distribution of continuous data between two groups. The Kruskal-Wallis rank-sum test was used for comparison between three groups. The χ2 test was used for comparing count data between groups. Results:Among the 73 cases with DILI caused by Polygonum multiflorum, 11 (15.1%) took a single herb of Polygonum multiflorum (including its powder and boiled water), 37 (50.7%) took traditional Chinese patent medicines containing Polygonum multiflorum, and 25 (34.2%) took a traditional Chinese medicine formula containing Polygonum multiflorum. The age of the DILI group caused by Polygonum multiflorum was 48 years old, which was lower than the other two groups (the DILI group caused by other traditional Chinese medicines: 55 years old, the DILI group caused by modern medicines: 52 years old; P<0.01). The levels of alanine aminotransferase (ALT), aspartate aminotransferase, and alkaline phosphatase were all higher than the other two groups ( P<0.05). The proportion of patients with antinuclear antibody positivity rate and severity of liver damage grade 3 was higher in the DILI group induced by Polygonum multiflorum than those in the modern drug-induced DILI group ( P<0.05). The liver cell injury type accounted for 96.6% (57/59) in the DILI group caused by Polygonum multiflorum, which was higher than that in the modern drug-induced DILI group (69.3%, 156/225) ( P<0.001). There was no statistically significant difference ( P>0.05) in gender, age, medication duration, and various biochemical indicators between patients with DILI caused by Polygonum multiflorum monotherapy and compound preparations in terms of compatibility. The ALT level in the DILI group caused by raw Polygonum multiflorum was higher than that in the DILI group caused by processed Polygonum multiflorum [the DILI group caused by raw Polygonum multiflorum: 1 289.0(921.8, 1 851.8)U/L, the DILI group caused by processed Polygonum multiflorum: 890.0(304.0,1 320.0)U/L; P<0.05] according to the comparison of processing methods. Conclusion:The degree of DILI caused by Polygonum multiflorum is more obvious than that caused by other drugs. There was no difference in the degree of DILI caused by the single and the compound formulation. However, the liver damage caused by raw Polygonum multiflorum was more severe than that caused by processed Polygonum multiflorum.

Objective A model for studying oral ulcers induced by betel nut-extract was constructed in rats.Changes in the structure and diversity of oral flora were observed to explore the involvement of oral flora and local inflammatory factors in the pathogenesis of oral ulcers induced by betel nut-extract and to provide theoretical support for the prevention and treatment of oral ulcers in the clinic.Methods Thirty SD rats were randomly divided into normal,model and intervention groups(Guilin watermelon cream,8 mg/d for 7 days),with 10 rats/group.The oral mucosa of rats was subcutaneously injected with 10 g/mL of betel nut-extract to generate an oral ulcer model.The histomorphological changes were observed,and ulcer area and ulcer scores were assessed.Local oral tissue tumor necrosis factor-α(TNF-α),interleukin(IL)-2 and IL-8 levels were determined.Oral mucosal tissues were sampled for HE staining and analyzed for the structural distribution of oral flora and the diversity of microbial communities using high-throughput sequencing method.Results Compared with rats in the normal group,those in the model group had an increased ulcer area,significantly increased ulcer scores(P＜0.01),and significantly increased levels of TNF-α,IL-2 and IL-8 in the oral mucosal tissues(P＜0.01).The amount Streptococcus(P＜0.05)and Veillonella(P＜0.001)in the oral saliva of the model group rats was significantly reduced.The model group rats showed oral mucosal epithelial cell hyperplasia or focal necrosis,mucosal lamina propria edema,and hemorrhage accompanied by mass neutrophil and monocyte infiltration.Compared with the model group rats,the intervention group rats had significantly reduced ulcerated area(P＜0.05,P＜0.01)and ulcer scores(P＜0.05).And oral mucosal tissue levels of TNF-α(P＜0.01),IL-2(P＜0.05)and IL-8(P＜0.05),as well as significantly increased Streptococcus(P＜0.001)and Veillonella(P＜0.01)and significantly reduced Staphylococcus(P＜0.01)in the oral saliva.The degree of lesions in the oral mucosal tissues was significantly improved in the intervention group.Conclusions Betel nut-extract can be used to successfully reproduce a rat model of oral ulcer,and it is speculated that the development of oral ulcers after exposure to betel nut-extract may be related to an imbalance in the oral flora and local tissue inflammatory mediators.