Objective:To identify the serotype and genotype characteristics of the first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province. Methods:The information of seven suspected cluster brucellosis cases reported in Lanping County, Nujiang Lisu Autonomous Prefecture in April 2023 were collected, blood samples were collected, and the strains were isolated and cultured. Serological methods were employed for brucellosis diagnosis, bacterial species identification was performed using BCSP31-PCR and AMOS-PCR. Multilocus locus variable-number tandem repeat analysis (MLVA) was conducted for strain genotyping, followed by phylogenetic analysis comparing the strains with those from other regions of China.Results:All seven cases were diagnosed with brucellosis, they were all villagers from the same village and had daily contact with sheeps. Four suspected Brucella strains were isolated, identified as Brucella melitensis biotype by BCSP31-PCR and AMOS-PCR. The four isolated strains exhibited identical MLVA-16 genotype, with MLVA-8 genotype 42 and MLVA-11 genotype 180, belonging to the Eastern Mediterranean lineage. Compared with the MLVA-16 of the isolated strains from other regions of China, the four isolated strains formed an independent cluster. Conclusion:The first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province is caused by Brucella melitensis biotype, and the four isolated strains have showed unique MLVA genotype.

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

Objective:To identify the serotype and genotype characteristics of the first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province. Methods:The information of seven suspected cluster brucellosis cases reported in Lanping County, Nujiang Lisu Autonomous Prefecture in April 2023 were collected, blood samples were collected, and the strains were isolated and cultured. Serological methods were employed for brucellosis diagnosis, bacterial species identification was performed using BCSP31-PCR and AMOS-PCR. Multilocus locus variable-number tandem repeat analysis (MLVA) was conducted for strain genotyping, followed by phylogenetic analysis comparing the strains with those from other regions of China.Results:All seven cases were diagnosed with brucellosis, they were all villagers from the same village and had daily contact with sheeps. Four suspected Brucella strains were isolated, identified as Brucella melitensis biotype by BCSP31-PCR and AMOS-PCR. The four isolated strains exhibited identical MLVA-16 genotype, with MLVA-8 genotype 42 and MLVA-11 genotype 180, belonging to the Eastern Mediterranean lineage. Compared with the MLVA-16 of the isolated strains from other regions of China, the four isolated strains formed an independent cluster. Conclusion:The first cluster infection of Brucella in Nujiang Lisu Autonomous Prefecture of Yunnan Province is caused by Brucella melitensis biotype, and the four isolated strains have showed unique MLVA genotype.

The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

H 1-antihistamines are widely used in the treatment of various allergic diseases, but there are still many challenges in the safe and rational use of H 1-antihistamines in pediatrics, and there is a lack of guidance on the prescription review of H 1-antihistamines for children.In this paper, suggestions are put forward from the indications, dosage, route of administration, pathophysiological characteristics of children with individual difference and drug interactions, so as to provide reference for clinicians and pharmacists.

Anti-seizure medications (ASMs) are the main therapy for epilepsy.There are many kinds of ASMs with complex mechanism of action, so it is difficult for pharmacists to examine prescriptions.This paper put forward some suggestions on the indications, dosage forms/routes of administration, appropriateness of usage and dosage, combined medication and drug interaction, long-term prescription review, individual differences in pathophysiology of children, and drug selection when complicated with common epilepsy, for the reference of doctors and pharmacists.

Objective:To investigate the value of hemorrhage after thrombolytic (HAT) score and neutrophil to lymphocyte ratio (NLR) in combination predicting symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Consective patients with AIS received intravenous thrombolysis with ateplase in Tianjin TEDA Hospital from January 2016 to December 2021 were retrospectively enrolled. sICH was defined as cerebral CT showing hemorrhage at any part of the brain after intravenous thrombolysis, and the National Institutes of Health Stroke Scale (NIHSS) score was increased by≥4 compared with the baseline, or there was a manifestation indicating clinical aggravation. Univariate analysis was used to compare the baseline data of sICH group and non-sICH group. A binary multivariate logistic regression model was used to determine the independent influencing factors of sICH. The receiver operating characteristic (ROC) curve was used to evaluate the value of HAT score and NLR in combination predicting sICH. Results:A total of 429 patients with AIS were enrolled. Univariate analysis showed that there were significant differences in atrial fibrillation, systolic blood pressure, NLR, HAT score and NIHSS score between the sICH group and the non-sICH group (all P<0.05). Multivariate analysis showed that NLR (odds ratio [ OR] 1.405, 95% confidence interval [ CI] 1.193-2.958), HAT score ( OR 1.512, 95% CI 1.207-3.169) and NIHSS score ( OR 1.221, 95% CI 1.082-2.634) had significant independent correlation with sICH after adjusting for atrial fibrillation and systolic blood pressure. The ROC curve showed that the areas under the curve of HAT score, NLR and their combination predicting sICH were 0.719 (95% CI 0.609-0.832), 0.723 (95% CI 0.618-0.835) and 0.854 (95% CI 0.765-0.931), respectively. The areas under the curve of the two methods in combination were significantly larger than those of the single method ( P=0.029 and 0.032, respectively), and their sensitivity and specificity were 74.1% and 83.5% respectively. Conclusion:Combined HAT score and NLR is of high value in predicting sICH after intravenous thrombolysis in patients with AIS, and has clinical application potential.

Objective : To investigate whether NaHS，a hydrogen sulfide donor，can improve myocardial injury in sepsis by inhibiting oxidative stress and activating the Xc －/ GPX4 signaling pathway in ferroptosis． Methods : Lipopolysacc-haride(LPS) induced H9c2 in rat cardiomyocytes to form an in vitro model of myocardial injury in sep- sis，which was divided into Control group，LPS group and LPS + NaHS group．The kits were applied to detect the changes of cardiomyocyte viability，Fe2 + ，LDH and CK-MB，determine the levels of oxidative stress indexes GSH and MDA，detect the changes of cellular ROS and mitochondrial membrane potential levels by fluorescent probes， and detect the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 by Western blot. Results: Compared with the Control group，H9c2 cell viability decreased，Fe2 + concentration increased ，GSH ，MDA and ROS levels increased，mitochondrial JC-1 monomer increased ，expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 decreased，and cell damage increased after LPS stimulation (P＜0. 05) ．Compared with the LPS group，NaHS attenuated LPS-induced H9c2 cell injury and elevated Fe2 + concentration，decreased the level of LPS-induced oxidative stress in H9c2 cells ，and increased the expression levels of ferroptosis regulatory proteins SLC7A11 and GPX4 (P＜0. 05 ) ． Conclusion The mechanism by which NaHS attenuates myocardial injury in sepsis may be related to the inhibition of oxidative stress and activation of the Xc －/ GPX4 signaling pathway in fer- roptosis.

Antipyretic-analgesics are currently one of the most prescribed drugs in children.The clinical application of antipyretic-analgesics for children in our country still have irrational phenomenon, which affects the therapeutic effect and even poses hidden dangers to the safety of children.In this paper, suggestions were put forward from the indications, dosage form/route, dosage suitability, pathophysiological characteristics of children with individual differences and drug interactions in the symptomatic treatment of febrile children, so as to provide reference for the general pharmacists when conducting prescription review.