BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Objective To explore relationship between glucose metabolism and neonatal weight in high-risk gestational diabetes melli-tus(GDM).Method A retrospective study was conducted on 779 pregnant women who underwent prenatal examinations at Tongzhou Maternity and Child Health Care Hospital in Beijing from March to June 2022.The data on pre-pregnancy weight,mid-and late-preg-nancy glycated albumin(GA)and glycated hemoglobin(HbA1c),pre-delivery weight,gestational weight gain,and neonatal birth weight were collected.A GDM risk assessment model was established using multivariate logistic regression to classify pregnant women into high-risk and low-risk groups for GDM,followed by separate management strategies.Regression discontinuity(RD)analysis was applied to evaluate the relationship between gestational glucose metabolism status and neonatal birth weight.Results Among the 779 pregnant women,the overall incidence of macrosomia was 7.32％.The high-risk GDM group exhibited significantly higher pre-pregnan-cy weight,late-pregnancy HbA1c,and GA levels compared to the low-risk group(all P＜0.001).Neonatal birth weight in the high-risk group was significantly higher than that in the low-risk group(P＜0.05),with a significantly increased macrosomia incidence(13.55％vs 5.77％,P＜0.05).RD analysis revealed a jump reduction of 199.59 g(P=0.029)in neonatal birth weight at the risk score thresh-old.Conclusion Lifestyle glucose metabolism management in high-risk GDM pregnant women may effectively reduce neonatal birth weight,mitigated the trend of excessive gestational weight gain,and improved late-pregnancy HbA1c and GA levels,providing evi-dence-based support for maternal and child health services.

Objective:To explore the specific mechanism of Baijiesan on microangiogenesis of wound after perianal abscess in rats by regulating RAS signal pathway.Methods:A total of 72 SD rats were divided into control group,model group,Baijiesan group and Baijiesan+farnesylthiosalicylic acid(FTS)group,with 18 rats in each group.Cut off the whole layer of skin on the back of rats.The model group,Baijiesan group and Baijiesan+FTS group were treated with fecal supernatant,while the control group was treated with normal saline.After the successful establishment of the model,Baijiesan+FTS group were treated with Baijiesan and received in-traperitoneal injection of FTS,while Baijiesan group were treated with Baijiesan only.The back wound images of rats were taken after successful modeling(day 0),4 days,8 days and 12 days after treatment,and the wound healing rate was calculated.After 4 days,8 days and 12 days of treatment,6 rats in each group were randomly selected and killed,the new wound healing tissue was removed,and the blood of abdominal aorta of rats after treatment for 12 days was collected.Histopathological morphology of wound tissue was observed by HE and Masson staining.Immunohistochemistry was used to detect the number of microvessels.ELISA was used to detect serum inflammatory markers.RAS signal pathway and angiogenesis-related molecules were detected by qRT-PCR and Western blot.Results:Compared with control group,the wound healing rate of model group,Baijiesan group and Baijiesan+FTS group decreased at each time point(P<0.05),while the number of microvessels,the levels of TNF-α,IL-1β,IL-6,RAS and Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were increased(P<0.05).Compared with model group and Baijiesan+FTS group,the wound healing rate,the number of microvessels,RAS,Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were further increased in Baijiesan group(P<0.05),while the levels of TNF-α,IL-1β and IL-6 were decreased(P<0.05).Conclusion:Baijiesan can reduce the level of wound inflamma-tion after operation of perianal abscess,and may enhance the ability of wound angiogenesis and wound healing by promoting RAS signal pathway.

BACKGROUND:Cognitive impairment is the most common complication after stroke,and its severity is closely related to the patient's prognosis.The prognosis of patients can be significantly improved if the severity of their cognitive impairment is recognized and targeted early.OBJECTIVE:To initially explore potential biomarkers affecting the progression of post-stroke cognitive impairment,thereby providing a richer and unique reference for the study of their pathophysiological mechanisms.METHODS:Using ultra performance liquid chromatography-mass spectrometry,non-targeted metabolomics analysis was conducted on serum samples from patients with mild and moderate post-stroke cognitive impairment to identify differential metabolites between the two groups.To further validate the diagnostic efficacy of the differential metabolites,the receiver operating characteristic curve analysis was used to evaluate their accuracy and sensitivity in distinguishing disease severity.In addition,pathway analysis was conducted on the differential metabolites.RESULTS AND CONCLUSION:(1)There were significant differences in metabolic profiles between patients with mild and moderate post-stroke cognitive impairment,and 9 differential metabolites were screened by the receiver operating characteristic curve.(2)Differential metabolite pathway analysis revealed that the metabolic pathways affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment included tryptophan metabolism,D-amino acid metabolism,biotin metabolism,retinol metabolism,aminoacyl-tRNA biosynthesis,lysine degradation,protein digestion and uptake,pyrimidine metabolism,cysteine and methionine metabolism,ABC transporter proteins,amino acid biosynthesis,and 2-oxocarboxylic acid metabolism.To conclude,9 potential biomarkers affecting disease progression in patients with mild-to-moderate post-stroke cognitive impairment have been identified,involving 12 metabolic pathways including tryptophan metabolism,D-amino acid metabolism and retinol metabolism.

Objective To explore relationship between glucose metabolism and neonatal weight in high-risk gestational diabetes melli-tus(GDM).Method A retrospective study was conducted on 779 pregnant women who underwent prenatal examinations at Tongzhou Maternity and Child Health Care Hospital in Beijing from March to June 2022.The data on pre-pregnancy weight,mid-and late-preg-nancy glycated albumin(GA)and glycated hemoglobin(HbA1c),pre-delivery weight,gestational weight gain,and neonatal birth weight were collected.A GDM risk assessment model was established using multivariate logistic regression to classify pregnant women into high-risk and low-risk groups for GDM,followed by separate management strategies.Regression discontinuity(RD)analysis was applied to evaluate the relationship between gestational glucose metabolism status and neonatal birth weight.Results Among the 779 pregnant women,the overall incidence of macrosomia was 7.32％.The high-risk GDM group exhibited significantly higher pre-pregnan-cy weight,late-pregnancy HbA1c,and GA levels compared to the low-risk group(all P＜0.001).Neonatal birth weight in the high-risk group was significantly higher than that in the low-risk group(P＜0.05),with a significantly increased macrosomia incidence(13.55％vs 5.77％,P＜0.05).RD analysis revealed a jump reduction of 199.59 g(P=0.029)in neonatal birth weight at the risk score thresh-old.Conclusion Lifestyle glucose metabolism management in high-risk GDM pregnant women may effectively reduce neonatal birth weight,mitigated the trend of excessive gestational weight gain,and improved late-pregnancy HbA1c and GA levels,providing evi-dence-based support for maternal and child health services.

Objective:To explore the specific mechanism of Baijiesan on microangiogenesis of wound after perianal abscess in rats by regulating RAS signal pathway.Methods:A total of 72 SD rats were divided into control group,model group,Baijiesan group and Baijiesan+farnesylthiosalicylic acid(FTS)group,with 18 rats in each group.Cut off the whole layer of skin on the back of rats.The model group,Baijiesan group and Baijiesan+FTS group were treated with fecal supernatant,while the control group was treated with normal saline.After the successful establishment of the model,Baijiesan+FTS group were treated with Baijiesan and received in-traperitoneal injection of FTS,while Baijiesan group were treated with Baijiesan only.The back wound images of rats were taken after successful modeling(day 0),4 days,8 days and 12 days after treatment,and the wound healing rate was calculated.After 4 days,8 days and 12 days of treatment,6 rats in each group were randomly selected and killed,the new wound healing tissue was removed,and the blood of abdominal aorta of rats after treatment for 12 days was collected.Histopathological morphology of wound tissue was observed by HE and Masson staining.Immunohistochemistry was used to detect the number of microvessels.ELISA was used to detect serum inflammatory markers.RAS signal pathway and angiogenesis-related molecules were detected by qRT-PCR and Western blot.Results:Compared with control group,the wound healing rate of model group,Baijiesan group and Baijiesan+FTS group decreased at each time point(P<0.05),while the number of microvessels,the levels of TNF-α,IL-1β,IL-6,RAS and Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were increased(P<0.05).Compared with model group and Baijiesan+FTS group,the wound healing rate,the number of microvessels,RAS,Raf-1,VEGF,VEGFR2 mRNA and protein,ERK1,ERK2 mRNA,p-MEK1/2,p-ERK1/2 protein expressions were further increased in Baijiesan group(P<0.05),while the levels of TNF-α,IL-1β and IL-6 were decreased(P<0.05).Conclusion:Baijiesan can reduce the level of wound inflamma-tion after operation of perianal abscess,and may enhance the ability of wound angiogenesis and wound healing by promoting RAS signal pathway.

Animals ; Callithrix ; Sex Factors ; Vocalization, Animal ; Sex Characteristics

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.

Objective:To report the clinical efficacy of adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures in patients with initially unresectable hepatocellular carcinoma.Methods:This is a retrospective case series study. Data from 100 patients who underwent adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical procedures with long-term survival were collected from December 2018 to December 2022 at the Faculty of Hepato-Pancreato-Biliary Surgery, First Medical Center, Chinese People′s Liberation Army General Hospital. According to inclusion and exclusion criteria, 47 cases were included, among which patients who met the discontinuation criteria and maintained a drug-free tumor-free status. Thirty-nine male and eight female patients were included, with an age of (54.2±18.8)years(range:38 to 73 years) at initial diagnosis. At the time of initial diagnosis, 43 cases (91.5%) were classified as Barcelona Clinic Liver Cancer stage C. Survival curves were made using Kaplan Meier method.Results:Forty-seven patients underwent R0 resection, all achieved a drug-free tumor-free state through postoperative adjuvant therapy based on pathological examination results. Thirty-six patients(76.6%) maintained a drug-free tumor-free survival status for more than 6 months,28 patients(59.6%) for more than 12 months,and 8 patients(17.0%) for more than 24 months. The longest drug-free tumor-free survival in this cohort reached 48 months. The median follow-up time in this study was 32 months. After diagnosis, the overall survival rates at 1- and 3- years were 97.7%(95% CI:93.4% to 100%) and 90.7%(95% CI:82.5% to 99.8%). The postoperative recurrence-free survival rates at 1- and 3- years were 91.0%(95% CI:83.0% to 99.8%) and 71.3%(95% CI:58.7% to 86.5%). Conclusions:The adjuvant therapy based on pathological results following immunotherapy combined with targeted therapy and sequential curative surgical approach provides long-term survival benefits for patients with initially unresectable hepatocellular carcinoma. Standardized adjuvant therapy maybe sustain long-term tumor-free status,and achieve drug-free tumor-free survival.