Objective To investigate the relationship between plasma metalloproteinase-tissue inhibitor 1 (TIMP-1),vascular endothelial growth factor (VEGF) and potentially transforming growth factor binding protein 2 (LTBP-2) levels and risk stratification and death in patients with acute pulmonary embolism (APE). Methods A toral of 110 APE patients admitted to the Third People's Hospital of Haikou from January 2022 to January 2024 were selected for risk stratification,and they were divided into low-risk group(n=28),medium-risk group(n=43) and high-risk groups(n=39). According to the occurrence of death in APE patients,they were divided into a survival group (n=79)and a death group(n=31). Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of plasma TIMP-1,VEGF and LTBP-2. Applying multiple Logistic regression analysis to identify risk factors affecting the mortality of APE patients and plotting ROC curve to analyze the predictive value of plasma TIMP-1,VEGF and LTBP-2 levels for APE patients mortality and. Pearson correlation analysis was used to analyze the correlation between plasma levels of TIMP-1,VEGF and LTBP-2 and clinical indexes in APE patients. Results The heart rate,B-type brain natriuretic peptide (BNP),D-dimer,TIMP-1(207.15±62.84pg/ml vs 152.48±41.62pg/ml),VEGF (726.35±190.46pg/ml vs 419.27±115.28pg/ml) and LTBP-2(29.17±6.38ng/ml vs 13.26±3.70ng/ml) levels in the death group were significantly higher than those in the survival group,the difference were statistically significant (t=5.386～21.194,all P<0.05). The levels of plasma TIMP-1(204.15±60.17 pg/ml,178.18±51.30pg/ml vs 148.20±34.80pg/ml),VEGF(720.83±204.18pg/ml,580.16±158.37pg/ml vs 412.15±109.26pg/ml) and LTBP-2(28.40±6.41ng/ml,21.37±5.26ng/ml vs 12.84±3.12ng/ml) in high-risk and medium-risk groups were significantly higher than those in the low-risk group(t=8.417～19.850),and those in the high-risk group were higher than those in the medium-risk group(t=7.964,9.381,11.470),the differences were statistically significant (all P<0.05),respectively. Multiple Logistic regression analysis showed that increased plasma BNP,D-dimer,TIMP-1,VEGF and LTBP-2 levels were risk factors for death in APE patients (all P<0.05). ROC curve analysis showed that TIMP-1,VEGF and LTBP-2 combined predicted the highest AUC(95％CI) of death in APE patients[0.938(0.881～0.997)],with an accuracy of 88.2％. Pearson correlation analysis showed that the levels of plasma TIMP-1,VEGF and LTBP-2 in APE patients were positively correlated with BNP and D-dimer (r=0.416～0.753,all P<0.05). Conclusion Elevated levels of plasma TIMP-1,VEGF and LTBP-2 are associated with high risk and mortality in APE,and the combination of these three factors has good predictive value for mortality in APE patients.

Objective:To explore the effect of Chaibei Zhixian Decoction on intestinal flora and T helper 17/regulatory T cell(Th17/Treg)immune balance in epileptic rats by regulating mammalian target of rapamycin/hypoxia-inducible factor-1α(mTOR/HIF-1α)pathway.Methods:Sixty rats were randomly divided into Sham group,Model group,low-dose Chaibei Zhixian Decoction group(CBZXD-Low)and high-dose Chaibei Zhixian Decoction group(CBZXD-High),with 15 rats in each group.Lateral ventricular injec-tion 1 μl kainic acid(1.5 μg/μl)was used to prepare epileptic rat model,Sham group was injected with an equal amount of physiological saline.CBZXD-Low group and CBZXD-High group were given Chaibei Zhixian Decoction by gavage daily(8.48 g/kg,16.96 g/kg),while Sham group and model group were given an equal amount of physiological saline by gavage.After continuous gavage for 4 weeks,HE staining and Nissl staining were used to detect pathological damage in hippocampal tissue;RT-qPCR was used to detect Th17/Treg related marker mRNA levels in spleen tissue and mTOR,HIF-1α mRNA levels in hippocampus tissue;flow cytometry was used to de-tect Th17/Treg cell ratio in spleen tissue;16S rRNA sequencing of feces in colon segment was performed;Western blot was used to de-tect mTOR and HIF-1α protein levels in hippocampal tissue.Results:Compared with Sham group,Model group rats suffered from spontaneous epilepsy,the arrangement of hippocampal neurons was disordered and severely lacking,intracellular Nissl bodies was de-creased,RORγt,IL-17A mRNA levels in spleen tissue were increased,Foxp3,CTLA-4 and GITR mRNA levels were decreased,the proportion of Th17 cells and Th17/Treg were increased,the proportion of Treg cell was decreased,intestinal flora α/β diversity were decreased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were increased,the proportion of beneficial bacte-ria such as Bacteroides,Lactobacillus,Prevotella and Akkermansia were decreased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levelsin hippocampal tissue were increased(P<0.05);compared with Model group,the seizures of rats in CBZXD-Low group and CBZXD-High group were significantly reduced,and the damage to hippocampal neurons was alleviated,RORγt,IL-17A mRNA levels in spleen tissue were decreased,Foxp3,CTLA-4 and GITR mRNA levels were increased,the propor-tion of Th17 cells and Th17/Treg were decreased,the proportion of Treg cell was increased,intestinal flora α/β diversity were in-creased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were decreased,the proportion of beneficial bacte-ria,such as Bacteroides,Lactobacillus,Prevotella,and Akkermansia were increased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levels in hippocampal tissue were decreased(P<0.05);and it showed a dose-dependent effect of Chaibei Zhixian Decoction(P<0.05).Conclusion:Chaibei Zhixian Decoction can restore intestinal flora and Th17/Treg cell immune balance in epileptic rats,it possibly plays a role by regulating mTOR/HIF-1α pathway.

Objective:To investigate the effect of asiaticoside on cognitive impairment in young epileptic rats by regulating SIRT1/AMPK signaling pathway.Methods:Young rats were randomly separated into Sham group,Model group,low-dose asiaticoside(20 mg/kg)group,high-dose asiaticoside(40 mg/kg)group and high-dose asiaticoside+EX527 group.The seizure situation of rats was observed;Morris water maze was applied to test spatial learning and memory abilities;ELISA was applied to detect levels of TNF-α,IL-10,IL-6,MDA,SOD and GSH-Px in rat hippocampal tissue;Nissl staining was applied to observe morphological changes of rat hippocampal tissue;TUNEL staining was applied to detect apoptosis of hippocampal neurons in rats;Western blot was applied to detect expressions of Cleaved-caspase-3,Bax,Bcl-2,SIRT1,p-AMPK and AMPK proteins in rat hippocampal tissue.Results:Compared with Sham group,Model group showed severe tissue damage in hippocampal CA1 region of rats,epilepsy score and seizure duration were obviously increased,incubation period was obviously prolonged,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously increased,the retention time and number of platform crossings were obviously decreased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1,p-AMPK/AMPK in CA1 region of hippocampus were obviously reduced(P<0.05);compared with Model group,tissue damage in hippocampal CA1 region of rats in low-dose and high-dose asiaticoside groups was obviously reduced,the epilepsy score and seizure duration were obviously decreased,incubation period was obviously shortened,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously reduced,the retention time and the number of platform crossings were obviously increased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1 and p-AMPK/AMPK in CA1 region of hippocampus were obviously increased(P<0.05);EX527 was able to partially reverse the improve-ment effect of asiaticoside on epileptic young rats.Conclusion:Asiaticoside can reduce inflammatory response,oxidative stress and hippocampal neuronal apoptosis in rats and reduce nerve damage by activating SIRT1/AMPK signaling pathway,thus improving cogni-tive function of young epileptic.

Objective To investigate the relationship between plasma metalloproteinase-tissue inhibitor 1 (TIMP-1),vascular endothelial growth factor (VEGF) and potentially transforming growth factor binding protein 2 (LTBP-2) levels and risk stratification and death in patients with acute pulmonary embolism (APE). Methods A toral of 110 APE patients admitted to the Third People's Hospital of Haikou from January 2022 to January 2024 were selected for risk stratification,and they were divided into low-risk group(n=28),medium-risk group(n=43) and high-risk groups(n=39). According to the occurrence of death in APE patients,they were divided into a survival group (n=79)and a death group(n=31). Enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of plasma TIMP-1,VEGF and LTBP-2. Applying multiple Logistic regression analysis to identify risk factors affecting the mortality of APE patients and plotting ROC curve to analyze the predictive value of plasma TIMP-1,VEGF and LTBP-2 levels for APE patients mortality and. Pearson correlation analysis was used to analyze the correlation between plasma levels of TIMP-1,VEGF and LTBP-2 and clinical indexes in APE patients. Results The heart rate,B-type brain natriuretic peptide (BNP),D-dimer,TIMP-1(207.15±62.84pg/ml vs 152.48±41.62pg/ml),VEGF (726.35±190.46pg/ml vs 419.27±115.28pg/ml) and LTBP-2(29.17±6.38ng/ml vs 13.26±3.70ng/ml) levels in the death group were significantly higher than those in the survival group,the difference were statistically significant (t=5.386～21.194,all P<0.05). The levels of plasma TIMP-1(204.15±60.17 pg/ml,178.18±51.30pg/ml vs 148.20±34.80pg/ml),VEGF(720.83±204.18pg/ml,580.16±158.37pg/ml vs 412.15±109.26pg/ml) and LTBP-2(28.40±6.41ng/ml,21.37±5.26ng/ml vs 12.84±3.12ng/ml) in high-risk and medium-risk groups were significantly higher than those in the low-risk group(t=8.417～19.850),and those in the high-risk group were higher than those in the medium-risk group(t=7.964,9.381,11.470),the differences were statistically significant (all P<0.05),respectively. Multiple Logistic regression analysis showed that increased plasma BNP,D-dimer,TIMP-1,VEGF and LTBP-2 levels were risk factors for death in APE patients (all P<0.05). ROC curve analysis showed that TIMP-1,VEGF and LTBP-2 combined predicted the highest AUC(95％CI) of death in APE patients[0.938(0.881～0.997)],with an accuracy of 88.2％. Pearson correlation analysis showed that the levels of plasma TIMP-1,VEGF and LTBP-2 in APE patients were positively correlated with BNP and D-dimer (r=0.416～0.753,all P<0.05). Conclusion Elevated levels of plasma TIMP-1,VEGF and LTBP-2 are associated with high risk and mortality in APE,and the combination of these three factors has good predictive value for mortality in APE patients.

Objective:To investigate the effect of asiaticoside on cognitive impairment in young epileptic rats by regulating SIRT1/AMPK signaling pathway.Methods:Young rats were randomly separated into Sham group,Model group,low-dose asiaticoside(20 mg/kg)group,high-dose asiaticoside(40 mg/kg)group and high-dose asiaticoside+EX527 group.The seizure situation of rats was observed;Morris water maze was applied to test spatial learning and memory abilities;ELISA was applied to detect levels of TNF-α,IL-10,IL-6,MDA,SOD and GSH-Px in rat hippocampal tissue;Nissl staining was applied to observe morphological changes of rat hippocampal tissue;TUNEL staining was applied to detect apoptosis of hippocampal neurons in rats;Western blot was applied to detect expressions of Cleaved-caspase-3,Bax,Bcl-2,SIRT1,p-AMPK and AMPK proteins in rat hippocampal tissue.Results:Compared with Sham group,Model group showed severe tissue damage in hippocampal CA1 region of rats,epilepsy score and seizure duration were obviously increased,incubation period was obviously prolonged,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously increased,the retention time and number of platform crossings were obviously decreased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1,p-AMPK/AMPK in CA1 region of hippocampus were obviously reduced(P<0.05);compared with Model group,tissue damage in hippocampal CA1 region of rats in low-dose and high-dose asiaticoside groups was obviously reduced,the epilepsy score and seizure duration were obviously decreased,incubation period was obviously shortened,levels of TNF-α,IL-6,MDA,neuronal apoptosis rate,expressions of Cleaved-caspase-3 and Bax proteins in CA1 region of hippocampus were obviously reduced,the retention time and the number of platform crossings were obviously increased,levels of IL-10,SOD,GSH-Px,protein expressions of Bcl-2,SIRT1 and p-AMPK/AMPK in CA1 region of hippocampus were obviously increased(P<0.05);EX527 was able to partially reverse the improve-ment effect of asiaticoside on epileptic young rats.Conclusion:Asiaticoside can reduce inflammatory response,oxidative stress and hippocampal neuronal apoptosis in rats and reduce nerve damage by activating SIRT1/AMPK signaling pathway,thus improving cogni-tive function of young epileptic.

Objective:To explore the effect of Chaibei Zhixian Decoction on intestinal flora and T helper 17/regulatory T cell(Th17/Treg)immune balance in epileptic rats by regulating mammalian target of rapamycin/hypoxia-inducible factor-1α(mTOR/HIF-1α)pathway.Methods:Sixty rats were randomly divided into Sham group,Model group,low-dose Chaibei Zhixian Decoction group(CBZXD-Low)and high-dose Chaibei Zhixian Decoction group(CBZXD-High),with 15 rats in each group.Lateral ventricular injec-tion 1 μl kainic acid(1.5 μg/μl)was used to prepare epileptic rat model,Sham group was injected with an equal amount of physiological saline.CBZXD-Low group and CBZXD-High group were given Chaibei Zhixian Decoction by gavage daily(8.48 g/kg,16.96 g/kg),while Sham group and model group were given an equal amount of physiological saline by gavage.After continuous gavage for 4 weeks,HE staining and Nissl staining were used to detect pathological damage in hippocampal tissue;RT-qPCR was used to detect Th17/Treg related marker mRNA levels in spleen tissue and mTOR,HIF-1α mRNA levels in hippocampus tissue;flow cytometry was used to de-tect Th17/Treg cell ratio in spleen tissue;16S rRNA sequencing of feces in colon segment was performed;Western blot was used to de-tect mTOR and HIF-1α protein levels in hippocampal tissue.Results:Compared with Sham group,Model group rats suffered from spontaneous epilepsy,the arrangement of hippocampal neurons was disordered and severely lacking,intracellular Nissl bodies was de-creased,RORγt,IL-17A mRNA levels in spleen tissue were increased,Foxp3,CTLA-4 and GITR mRNA levels were decreased,the proportion of Th17 cells and Th17/Treg were increased,the proportion of Treg cell was decreased,intestinal flora α/β diversity were decreased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were increased,the proportion of beneficial bacte-ria such as Bacteroides,Lactobacillus,Prevotella and Akkermansia were decreased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levelsin hippocampal tissue were increased(P<0.05);compared with Model group,the seizures of rats in CBZXD-Low group and CBZXD-High group were significantly reduced,and the damage to hippocampal neurons was alleviated,RORγt,IL-17A mRNA levels in spleen tissue were decreased,Foxp3,CTLA-4 and GITR mRNA levels were increased,the propor-tion of Th17 cells and Th17/Treg were decreased,the proportion of Treg cell was increased,intestinal flora α/β diversity were in-creased,the proportion of harmful bacteria such as Cronobacter and Heliobacillus were decreased,the proportion of beneficial bacte-ria,such as Bacteroides,Lactobacillus,Prevotella,and Akkermansia were increased;mTOR and HIF-1α mRNA levels,p-mTOR/mTOR,HIF-1α protein levels in hippocampal tissue were decreased(P<0.05);and it showed a dose-dependent effect of Chaibei Zhixian Decoction(P<0.05).Conclusion:Chaibei Zhixian Decoction can restore intestinal flora and Th17/Treg cell immune balance in epileptic rats,it possibly plays a role by regulating mTOR/HIF-1α pathway.

Cow′s milk protein allergy is the most common food allergy in infants and young children, and its prevalence has been increasing in recent years. The use of appropriate diagnostic methods is essential for the management of patients. Oral food challenges are not yet widely used in clinical practice, and new and more effective methods are still being sought, including component resolved diagnosis. Component resolved diagnosis has been introduced into the field of clinical allergy, which provides a new understanding for the diagnosis and treatment of allergic diseases. This article reviews the clinical application of component resolved diagnosis in IgE-mediated cow′s milk protein allergy, especially the components of cow′s milk protein allergy and the identification of co-sensitization, the research progress of diagnosis, the prediction of the development of tolerance and the risk of allergic reactions, the guidance of allergen immunotherapy and the development of personalized diet for patients, in order to provide a basis for the diagnosis, treatment and prevention of IgE-mediated cow′s milk protein allergy.

Objective To compare seminal carnitine levels between normal males and asthenozoospermic patients,evaluate its correla-tion with progressive motility(PR)of sperm,and observe the effects of exogenous carnitine supplementation on asthenozoospermic pa-tients.Methods Semen samples were collected from 511 normal fertile males and asthenozoospermic patients.Seminal was measured using a fixed-time assay kit and the levels of carnitine were compared between the two groups.The consistency between seminal carni-tine and PR was assessed.Additionally,77 asthenozoospermic patients received L-carnitine(1 g/time,3 times/day,30 days/course).The levels of seminal carnitine and PR alteration pre-and post-treatment were monitored.Results The seminal L-carnitine level in the patients with asthenospermia([194.34±65.41]μmol/L)was significantly lower than that in normal fertile males([405.43±72.12]μmol/L)(P＜0.01).When the seminal L-carnitine level ≥325 μmol/L was set as the threshold,the statistical results showed that Kappa value was 0.81,with a diagnostic coincidence rate of 93.74％.After one course of administration of L-carnitine,the concentra-tion of seminal L-carnitine([356.03±84.87]μmol/L)and PR([32.69±8.35]％)were significantly higher those that before treat-ment([183.61±79.54]μmol/L and[16.56±7.74]％,P＜0.01).Conclusion The seminal carnitine assay kit could be used for ac-curate and high-throughput quantification of clinical samples,facilitating asthenozoospermia diagnosis and therapeutic efficacy evalua-tion.Exogenous carnitine supplementation may elevate seminal carnitine levels and sperm motility in asthenozoospermic patients and po-tentially improve their fertility.

Cow′s milk protein allergy is the most common food allergy in infants and young children, and its prevalence has been increasing in recent years. The use of appropriate diagnostic methods is essential for the management of patients. Oral food challenges are not yet widely used in clinical practice, and new and more effective methods are still being sought, including component resolved diagnosis. Component resolved diagnosis has been introduced into the field of clinical allergy, which provides a new understanding for the diagnosis and treatment of allergic diseases. This article reviews the clinical application of component resolved diagnosis in IgE-mediated cow′s milk protein allergy, especially the components of cow′s milk protein allergy and the identification of co-sensitization, the research progress of diagnosis, the prediction of the development of tolerance and the risk of allergic reactions, the guidance of allergen immunotherapy and the development of personalized diet for patients, in order to provide a basis for the diagnosis, treatment and prevention of IgE-mediated cow′s milk protein allergy.

Malignant tumors are diseases that seriously threaten human health and social development. Traditional tumor therapies such as surgery, radiotherapy, chemotherapy and targeted therapy cannot fully meet the needs of clinical treatment, and emerging immunotherapy has become a research hotspot in the field of tumor treatment. Immune checkpoint inhibitors (ICIs) have been approved as a tumor immunotherapy method for the treatment of various tumors, such as lung cancer, liver cancer, stomach cancer and colorectal cancer, etc. However, during the clinical use of ICIs, only a small number of patients experienced durable responses, which also led to drug resistance and adverse reactions. Therefore, the identification and development of predictive biomarkers is crucial to improve the therapeutic efficacy of ICIs. The predictive biomarkers of tumor ICIs mainly include tumor biomarkers, tumor microenvironment biomarkers, circulation-related biomarkers, host environmental biomarkers and combinatorial biomarkers. They are of great significance for screening, individualized treatment and prognosis evaluation of tumor patients. This article reviews the advances of predictive markers for tumor ICIs therapy.
Humans ; Immune Checkpoint Inhibitors/therapeutic use* ; Lung Neoplasms ; Biomarkers ; Immunotherapy/methods* ; Biomarkers, Tumor/genetics* ; Prognosis ; Tumor Microenvironment