1.Correlation between estrogen metabolism of intestinal flora and liver fibrosis based on fecal microbiota transplantation
Na PAN ; Xue-ping QI ; Hui-jie SHENG ; Xiao-yu LYU ; Lu-yao GAO ; Hao-yang CHEN ; Yan-yan YIN ; Jia-jia WANG
Chinese Pharmacological Bulletin 2025;41(8):1508-1516
Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.
2.Observation of the Effect of Sodium Cantharinate Assisted Bevacizumab in the Treatment of Advanced Non Small Cell Lung Cancer Patients
Jia-sheng ZHAO ; Lei WANG ; Li LI ; Yong LIANG ; Hong-ying YIN
Progress in Modern Biomedicine 2025;25(11):1830-1837
Objective:To observe the effect of sodium cantharidate assisted bevacizumab in the treatment of advanced non-small cell lung cancer patients.Methods:A total of 120 patients with advanced lung adenocarcinoma from January 2021 to December 2023 were divided into two groups,namely the experimental group and the matched group,each consisting of 60 cases.All patients were treated with AP(cisplatin+pemetrexed)chemotherapy,and bevacizumab(7.5 mg/kg)was administered intravenously at the same time as chemotherapy in the matched group,while sodium bengalate(0.5 mg)was added intravenously in the experimental group on the basis of the matched group,and the patients in the two groups were compared with each other in terms of the clinical efficacy of the two groups in a cycle of 21 d,and the changes in the indicators of the immune function,symptoms and scores of adverse reactions were also compared before and after the 4 consecutive cycles of treatment.After 4 consecutive cycles of treatment,we compared the clinical efficacy,immune function indexes,symptoms,and the incidence of adverse reactions.Results:There was no difference in disease control rate(P>0.05),and the objective response rate was higher than the matched group(P<0.05);Pretherapy,tthe levels of natural killer(NK)cells,CD4+/CD8+,immunoglobulin(Ig)G and IgA were different between the test and matched group(P>0.05).Post-treatment,the levels of NK cells,CD4+/CD8+,IgG,and IgA in the experimental group increased,while there was no significant change in the matched group.The experimental group was higher than the matched group(P<0.05);Pretherapy,there was no difference in VAS and BFI scores between the experimental group and the matched group(P>0.05).Post-treatment,the scores of the Simplified Fatigue Scale(BFI)and Visual Analog Scale(VAS)in both groups decreased,and the experimental group was lower than the matched group(P<0.05);The incidence of grade Ⅰ-Ⅱ gastrointestinal reactions,liver and kidney dysfunction,bone marrow suppression,leukopenia,and grade Ⅲ-Ⅳ bone marrow suppression in the experimental group were all lower than those in the matched group(P<0.05).Conclusion:Sodium cantharidate assisted bevacizumab therapy has a significant effect on non-small cell lung cancer.Compared with single chemotherapy combined with bevacizumab,it can improve the objective remission rate of patients,improve their immune function level,alleviate pain and cancer-related fatigue symptoms,and assist in reducing the incidence of adverse reactions caused by bevacizumab and chemotherapy.
3.ALKBH5 mediated m6A modification of NLRP3 promotes cardiomyocytes pyroptosis in mice with myocardial infarction
Miao-miao ZHAI ; Jian-jian YIN ; Zhi-mo WANG ; Yue-jiao ZHOU ; Qing-wen YU ; Pei WANG ; Li-rong ZHANG ; Sheng-na HAN
Chinese Pharmacological Bulletin 2025;41(3):434-444
Aim To investigate the effects of m6A demethylase ALKBH5 on cardiomyocytes pyroptosis in mice with myocardial infarction(MI).Methods The MI model of left anterior descending coronary artery ligation surgery was established by knocking down ALKBH5 using adeno-associated virus,and the hypox-ia model of mouse cardiomyocytes(HL-1)was estab-lished by knocking down small interfering RNA.The effects of ALKBH5 on the pyroptosis of MI mice and hypoxic HL-1 cells were observed.Subsequently,mechanism studies were conducted at the cellular lev-el,and the binding of ALKBH5 and IGF2BP2 to NL-RP3 mRNA was detected through RNA pull down and RNA immunoprecipitation(RIP)experiments.The MeRIP-qPCR method was used to determine the effects of ALKBH5 on the mRNA m6A level of NLRP3.Acti-nomycin D for RNA stability experiments were conduc-ted to detect the effects of ALKBH5 and IGF2BP2 on the stability of NLRP3 mRNA.Results Knocking down ALKBH5 in vivo and in vitro both inhibited NL-RP3 inflammasome activation and alleviated pyroptosis in MI mice and hypoxic HL-1 cells.Mechanistically,the results showed that NLRP3 mRNA could bind to ALKBH5 protein in HL-1 cells;knocking down ALK-BH5 could increase the m6A level of NLRP3 and re-duce the stability of NLRP3 mRNA;subsequently,it was confirmed that NLRP3 mRNA and IGF2BP2 pro-tein bound to each other;knocking down IGF2BP2 in-creased the mRNA stability of NLRP3.The Rescue ex-periment showed that knocking down IGF2BP2 re-versed the decrease in NLRP3 mRNA expression caused by knocking down ALKBH5.Conclusions ALKBH5 mediated m6A modification of NLRP3 pro-motes cardiomyocytes pyroptosis in mice with myocardi-al infarction.
4.Predictive value of caliceal pelvic height-to-infundibular length ratio for stone-free rate in lower calyx stone treatment with flexible ureteroscopic lithotripsy
Shiwei HUANG ; Sheng ZHONG ; Guangming YIN ; Long WANG ; Zhiqiang JIANG ; Kai HUANG ; Jing TAN
Chinese Journal of Urology 2025;46(8):600-606
Objective:This study aims to explore the predictive value of the ratio of caliceal pelvic height to infundibular length(CPH/IL)for the stone-free rate(SFR)in the treatment of lower calyx stones using flexible ureteroscopic lithotripsy(FURL)combined with a distally bendable negative pressure suction sheath.Methods:A retrospective analysis was conducted on the clinical data and anatomical parameters of 312 patients with lower calyx stones or combined lower calyx stones admitted to the Third Xiangya Hospital of Central South University from September 2022 to December 2023,all of whom were treated with FURL combined with a distally bendable negative pressure suction sheath. Stone clearance was defined as no residual stones or residual stones with a diameter of ≤3 mm without any symptoms. Patients were divided into the clearance group(265 cases,84.90%)and the non-clearance group(47 cases,15.10%). There were no significant differences in gender(male/female:173/92 cases vs. 29/18 cases),age[(44.69 ± 13.14)years vs.(42.60 ± 10.93)years],degree of hydronephrosis(no hydronephrosis/mild hydronephrosis/moderate to severe hydronephrosis:122/85/58 cases vs. 21/12/14 cases),side of lower calyx stones(left/right:157/108 cases vs. 31/16 cases),maximum diameter of stones(MDS)[(19.23 ± 6.41)mm vs.(17.77 ± 6.18)mm],and CT value of stones[(993.46 ± 249.12)Hu vs.(1013.43 ± 300.90)Hu]between the two groups( P > 0.05),indicating comparability between groups. There was no significant difference in the distance from the midpoint of the lower lip of the renal pelvis to the ureter at the lowest plane of the lower calyx(K-A line)between the clearance and non-clearance groups[(26.16 ± 5.18)mm vs.(25.70 ± 8.66)mm, P > 0.05]. However,significant differences were observed in the infundibulopelvic angle(IPA)[(53.97 ± 15.72)° vs.(37.43 ± 15.39)°],infundibular length(IL)[(27.26 ± 5.11)mm vs.(33.04 ± 7.38)mm],infundibular width(IW)[(8.27 ± 2.82)mm vs.(7.09 ± 3.20)mm],caliceal pelvic height(CPH)[(19.96 ± 4.63)mm vs.(30.32 ± 7.56)mm],ureter-lower calyx distance(ULD)[(23.00 ± 5.59)mm vs.(18.78 ± 6.31)mm],CPH/IL ratio[(0.73 ± 0.11)vs.(0.92 ± 0.09)],and curvature of the lower calyx of the renal pelvis[(0.06 ± 0.01)mm -1 vs.(0.08 ± 0.03)mm -1]between the two groups( P <0.05). Univariate and logistic multivariate regression analyses were used to identify the independent risk factors affecting the postoperative SFR of FURL-treated lower calyx stones and to assess the value of CPH/IL for SFR in the treatment of lower calyx stones using FURL combined with a distally bendable negative pressure suction sheath. A logistic multivariate regression model and a corresponding nomogram were constructed,and the predictive ability of the model for SFR was evaluated using the receiver operating characteristic(ROC)curve. The calibration curve and the Hosmer -Lemeshow test were used to assess the consistency and accuracy of the model. The clinical utility of the model was evaluated using decision curve analysis(DCA). Results:Univariate analysis revealed that seven anatomical parameters differed significantly between the clearance and non-clearance groups(all P < 0.05):infundibulopelvic angle(IPA, OR = 0.27,95% CI 0.17-0.42, P < 0.01),infundibular length(IL, OR = 2.52,95% CI 1.83-3.47, P < 0.01),infundibular width(IW, OR = 0.64,95% CI 0.45-0.90, P = 0.011),caliceal pelvic height(CPH, OR = 5.78,95% CI 3.67-9.10, P < 0.01),ureter-lower calyx distance(ULD, OR = 0.43,95% CI 0.30-0.63, P < 0.01),CPH/IL ratio( OR = 13.62,95% CI 6.86-27.03, P < 0.01),and curvature of the lower calyx of the renal pelvis( O = 3.15,95% CI 2.08-4.78, P < 0.01). Multivariate logistic regression further identified CPH/IL( OR = 9.87,95% CI 4.92-19.79, P < 0.01),IPA( OR = 0.41,95% CI 0.23-0.71, P = 0.001),and ULD( OR = 0.50,95% CI 0.29-0.87, P = 0.014)as independent risk factors influencing the stone-free rate after flexible ureteroscopic lithotripsy combined with a distally bendable negative-pressure suction sheath. The area under the ROC curve(AUC)of the univariate regression model showed that for IPA,the AUC was 0.788(95% CI 0.711-0.864);for IL,it was 0.731(95% CI 0.643-0.819);for ULD,it was 0.677(95% CI 0.586-0.767);for CPH,it was 0.867(95% CI 0.804-0.929);for IW,it was 0.628(95% CI 0.535-0.721);for CPH/IL,it was 0.906(95% CI 0.850-0.961)with an optimal cutoff value of 0.882,corresponding to a sensitivity of 83.02% and a specificity of 92.08%;and for curvature of the lower calyx of the renal pelvis,it was 0.744(95% CI 0.662-0.827). The AUC of the multivariate regression model was 0.929(95% CI 0.884-0.974)with an optimal cutoff value of 0.364,corresponding to a sensitivity of 82.98% and a specificity of 95.09%. Calibration curves demonstrated close agreement between the predicted and actual stone-free rates after FURL(C-index = 0.921). The Hosmer-Lemeshow goodness-of-fit test indicated no significant discrepancy between predicted and observed probabilities( P = 0.135,>0.05). Decision-curve analysis further revealed that basing clinical decisions on the model ,s predicted probability yields a higher net clinical benefit than either withholding FURL for all patients or treating all patients regardless of risk,and it also outperforms strategies guided by any single independent predictor alone. Conclusions:IPA,IL,IW,CPH,ULD,CPH/IL ratio,and curvature of the lower calyx of the renal pelvis can all predict the postoperative SFR of FURL combined with a distally bendable negative pressure suction sheath for the treatment of lower calyx stones to varying degrees. Among them,CPH/IL has the highest predictive value. When CPH/IL >0.88,it may be difficult to use FURL to treat lower calyx stones.
5.Diagnosis and Treatment of a Case of Spironolactone-Associated Asymptomatic Hyperuricemia After Renal Transplantation
Yun XIAO ; Xiaoyu HAN ; Chao ZHENG ; Yu FU ; Hanbin XIONG ; Bin ZOU ; Baolin WANG ; Hua ZOU ; Chenglong YIN ; Zhengyao JIANG ; Sheng ZOU ; Anle DU ; Guohui LI ; Xiaohui GUO ; Lin ZHONG ; Jiake HE
Herald of Medicine 2025;44(10):1562-1565
Objective To explore the identification method,pathogenesis,clinical characteristics and individualized pharmacotherapy of asymptomatic hyperuricemia after renal transplantation.Methods The pharmacist was on duty at the organ transplant outpatient clinic.During this time,they analyzed and sorted out the medications,identified and differentiated a case of asymptomatic hyperuricemia related to spironolactone in a patient who had undergone a renal transplant,and provided comprehensive care throughout the entire process.Results The asymptomatic hyperuricemia in this patient might be associated with spironolactone,and the adverse reactions of the patient were alleviated by pharmacists through optimizing clinical treatment.Up to now,no hyperuricemia occurred.Conclusions Pharmacists are required to collaborate closely with clinicians to establish medication profiles for patients under long-term follow-up and to closely monitor and evaluate drug-related adverse reactions.Additionally,they should assess the renal function and immune status of transplant recipients promptly and formulate individualized treatment plans in order to enhance the long-term survival of both the transplanted kidneys and the recipients.
6.Isolation,identification,and biological characterization of a Streptococcus equinus strain from sheep
Hai-li WANG ; Xiu-sheng YIN ; Qi JIA ; Feng-yuan ZHANG ; Ling MO ; Lin LI ; Jing DONG ; Jin-liang WANG
Chinese Journal of Zoonoses 2025;41(6):641-647
Streptococcus equinus is a zoonotic disease that can cause illness in various animals under specific environmental condi-tions.No reports have described isolation of this bacterium from the liver in affected sheep.This study successfully isolated and identi-fied a strain of Streptococcus equinus through bacterial isolation and culture,Gram staining,drug sensitivity testing,mouse sensitivity testing,bacterial biochemical testing,and whole genome sequencing.The strain was found to have pathogenicity toward Kunming white mice,and to be sensitive to four antibiotics(penicillin,ampicillin,ceftiofur sodium,and ceftriaxone sodium)but resistant to four antibiotics(streptomycin,amoxicillin,tetracycline,and gentamicin).On the basis of drug sensitivity testing,targeted treatment of the affected sheep flock with ceftiofur sodium effectively controlled the disease within 2 days,and no new cases occurred.This study provides a reference for biological characterization of ovine Streptococcus equinus;public health;and the investigation of disease pre-vention,control,and epidemiology.
7.Original plants, production areas, and spread of Sanqi: based on historical materials of the Ming and Qing Dynasties.
Mei WANG ; Min-Zhen YIN ; Hua-Sheng PENG
China Journal of Chinese Materia Medica 2025;50(11):2938-2944
Sanqi is first recorded in the Compendium of Materia Medica(Ben Cao Gang Mu) in the Ming Dynasty. During the Ming and Qing Dynasties, Sanqi, as a precious Dao-di herb, was successively spread and introduced for cultivation. This study verified the germplasm resources, production areas, and spread of Sanqi in the Ming and Qing Dynasties by systematically reviewing the historical materials, such as materia medica works and local chronicles, and the modern distribution of production areas. In the Ming and Qing Dynasties, the original plants of Sanqi included Panax notoginseng, P. japonicus, P. bipinnatifidus, P. zingiberensis, P. stipuleanatus, and Gynura japonica. Among them, the production area of P. notoginseng has changed. From 1578 to 1593, the main production areas of P. notoginseng were Nandan county, Hechi city in Guangxi Zhuang autonomous region and Guangnan county and Funing county, Wenshan prefecture in Yunnan province. From 1683 to 1755, the production areas of P. notoginseng additionally included Yizhou district, Tian'e county, and Huanjiang county in Hechi city, and Tianyang district and Tiandong county in Baise city, Xincheng county and Gongcheng county in Guangxi Zhuang autonomous region. From 1765 to 1892, the production areas additionally included Youjiang district, Debao county, Napo county, and Jingxi city in Baise city, and Tiandeng county in Guangxi Zhuang autonomous region, and Wenshan city, Malipo county, Yanshan county, Xichou county, and Maguan county in Wenshan prefecture, and Baoshan city, Dali prefecture, Lincang city, Honghe prefecture, Mangshi city, and Lushui city in Yunnan province. During the Wanli period of the Ming Dynasty, Sanqi was introduced to Zhejiang province. During the Qianlong period of the Qing Dynasty, it was introduced to Fujian province. During the Daoguang period of the Qing Dynasty, it was introduced to Hunan province. By comprehensively reviewing the materia medica works, local chronicles, and novel historical materials, this study restores the development history of the Sanqi industry in the Ming and Qing Dynasties. Historical data show that the introduction of Dao-di herbs should consider the biological characteristics of medicinal plants and avoid blind introduction.
China
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Drugs, Chinese Herbal/history*
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History, 17th Century
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History, 16th Century
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Plants, Medicinal/chemistry*
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Medicine, Chinese Traditional/history*
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History, 18th Century
8.Asian consensus on normothermic intraperitoneal and systemic treatment for gastric cancer with peritoneal metastasis
Zhenggang ZHU ; Kitayama Joji ; Hyung-Ho Kim ; Jimmy Bok-Yan So ; Hui CAO ; Lin CHEN ; Xiangdong CHENG ; Jiankun HU ; Imano Motohiro ; Ishigami Hironori ; Ye Seob Jee ; Jong-Han Kim ; Yasuhiro Kodera ; Han LIANG ; Xiaowen LIU ; Sheng LU ; Yiping MOU ; Mingming NIE ; Won Jun Seo ; Yanong WANG ; Dan WU ; Zekuan XU ; Yamaguchi Hironori ; Chao YAN ; Zhongyin YANG ; Kai YIN ; Yonemura Yutaka ; Wei-Peng Yong ; Jiren YU ; Jun ZHANG ; Asian Gastric Cancer NIPS Treatment Collaborative Group ; Shanghai Anticancer Association, Committee of Peritoneal Tumor
Journal of Surgery Concepts & Practice 2025;30(4):277-294
Gastric cancer with peritoneal metastasis (GCPM) is a common and lethal manifestation of advanced gastric cancer, with a median survival of only 5-11 months. This consensus was developed by 30 experts from Asia (China, Japan, Korea, and Singapore) using the Delphi method and the GRADE evidence grading system. A total of 29 statements were formulated, covering the diagnosis and assessment of GCPM, indications for laparoscopic exploration and NIPS (normothermic intraperitoneal and systemic treatment), treatment regimens, prevention and management of complications, criteria for conversion surgery, and postoperative intraperitoneal therapy. The consensus aims to standardize clinical practice and improve the prognosis of patients with GCPM.
9.Correlation between estrogen metabolism of intestinal flora and liver fibrosis based on fecal microbiota transplantation
Na PAN ; Xue-ping QI ; Hui-jie SHENG ; Xiao-yu LYU ; Lu-yao GAO ; Hao-yang CHEN ; Yan-yan YIN ; Jia-jia WANG
Chinese Pharmacological Bulletin 2025;41(8):1508-1516
Aim To study the correlation between es-trogen metabolism function of intestinal flora and liver fibrosis disease phenotype and differential intestinal bacteria by fecal microbiota transplantation(FMT).Methods C57BL/6J male mice were divided into normal group(Control-M),liver fibrosis Model group(Model),FMT-1 group(normal mice fecal microbiota transplantation from liver fibrosis mice),and FMT-2 group(liver fibrosis mice fecal microbiota transplanta-tion from female mice).The model group was induced by high fat and high glucose combined with low dose of CCl4 for 16 weeks.In the FMT group,the bacteria were destroyed by mixed antibacterial solution and then the corresponding fecal microbiota solution was given.The model group was established in the FMT-2 group and the model group at the same time.Liver function(ALT,AST)was detected by biochemical methods;liver inflammation(IL-1α,IL-6)was detected by ELISA;liver pathology was detected by HE and Mas-son methods;the expressions of α-SMA,collagen Ⅰ,estrogen receptor ERα,ERβ and GPER were detected by Western blot;estrogen metabolic enzymes β-glucu-ronidase and β-glucosidase in intestinal flora were de-tected by double antibody sandwich assay;gut microbi-ota was detected by 16S rDNA method;the correlation between estrogen metabolic enzymes,estrogen receptors and disease phenotypes and disease-related differential bacteria was analyzed by Pearson correlation analysis.Results Liver function,inflammation and fibrosis in-dices were significantly higher in the model group than those in the control-M group and significantly lower in the FMT-2 group than in the model group;estrogen metabolic enzymes of the intestinal flora significantly increased in the model group compared to the control-M group and significantly decreased in the FMT-2 group compared to the model group;the model group showed a significant increase in ERβ and GPER and a significant decrease in ERα compared to the control-M group,while the FMT-2 group showed a significant de-crease in ERβ and GPER and a significant increase in ERα compared to the model group;the FMT-2 group increased the enterobacterial abundance and diversity reduced by modelling;estrogen metabolic enzymes,es-trogen receptor ERβ and GPER were all positively cor-related with the disease phenotype,while the opposite was true for ERα;estrogen metabolic enzymes were positively correlated with Allobaculum,Ruminococcus and Alistipes,and negatively correlated with Akkerman-sia,Lactobacillus and Prevotella.Conclusions Fecal microbiota transplantation in female mice can alleviate liver fibrosis in male mice,which is related to the im-provement of estrogen metabolism of intestinal flora.
10.Isolation,identification,and biological characterization of a Streptococcus equinus strain from sheep
Hai-li WANG ; Xiu-sheng YIN ; Qi JIA ; Feng-yuan ZHANG ; Ling MO ; Lin LI ; Jing DONG ; Jin-liang WANG
Chinese Journal of Zoonoses 2025;41(6):641-647
Streptococcus equinus is a zoonotic disease that can cause illness in various animals under specific environmental condi-tions.No reports have described isolation of this bacterium from the liver in affected sheep.This study successfully isolated and identi-fied a strain of Streptococcus equinus through bacterial isolation and culture,Gram staining,drug sensitivity testing,mouse sensitivity testing,bacterial biochemical testing,and whole genome sequencing.The strain was found to have pathogenicity toward Kunming white mice,and to be sensitive to four antibiotics(penicillin,ampicillin,ceftiofur sodium,and ceftriaxone sodium)but resistant to four antibiotics(streptomycin,amoxicillin,tetracycline,and gentamicin).On the basis of drug sensitivity testing,targeted treatment of the affected sheep flock with ceftiofur sodium effectively controlled the disease within 2 days,and no new cases occurred.This study provides a reference for biological characterization of ovine Streptococcus equinus;public health;and the investigation of disease pre-vention,control,and epidemiology.

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