Sepsis-associated encephalopathy (SAE) is a common complication of sepsis, referring to a diffuse brain dysfunction caused by sepsis in the absence of direct central nervous system (CNS) infection. SAE occurs in up to 70% of patients with sepsis. Globally, the annual incidence of sepsis ranges from 30.0 to 48.9 million cases, resulting in approximately 11 million deaths per year, which accounts for 20% of all global mortalities. SAE is identified as an independent risk factor contributing to the increased mortality rate among these patients. Early diagnosis of SAE and related cerebral protection interventions hold significant clinical importance. Currently, the main indicators of brain function for sepsis patients include Glasgow coma score (GCS), confusion assessment method for the intensive care unit (CAM-ICU), electroencephalogram (EEG), brain CT or magnetic resonance imaging (MRI) and other related imaging changes, which have the problems of low sensitivity, poor specificity, and non-objective evaluation of the results of the diagnosis of SAE. This article focuses on the latest progress in the pathogenesis of SAE and systematically reviews potential biomarkers related to the onset of SAE from multiple aspects, including inflammatory markers, endothelial and neuronal injury markers, and metabolic markers. This will provide new insights for the clinical diagnosis and treatment of SAE.
Humans ; Sepsis-Associated Encephalopathy/therapy* ; Biomarkers ; Sepsis/complications* ; Magnetic Resonance Imaging ; Electroencephalography ; Brain Diseases/etiology*

Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.

OBJECTIVE To analyze the characteristics of pediatric medicines with priority review and approval for marketing in China,providing a reference for promoting enterprise R&D and production,as well as improving the supply guarantee mechanism for pediatric medicines.METHODS Based on publicly available data sources such as List of Approved Information for Pediatric Medications Subject to Priority Review and Approval,Pharnexcloud biomedical database,and National Medical Insurance Drug Directory,this study conducted a comprehensive analysis of the main characteristics of pediatric medicines with priority review and approval for marketing.RESULTS As of June 30,2024,a total of 68 pediatric medicines had been approved through the priority review and approval process,covering 12 therapeutic areas,with oral dosage forms accounting for 64.71％.The median time from application to inclusion in priority review was 35.50 days,with an average of 41.69 days.The median time from inclusion in priority review to market approval was 1.24 years,with an average of 1.42 years.This included 12 domestic new medicines,21 domestic generic medicines,35 imported medicines,as well as 29 pediatric-specific medicines and 21 orphan medicines.Additionally,31 of these medicines had been included in the medical insurance catalog,representing a proportion of 45.59％.CONCLUSIONS Currently,a trend of differentiated competition is emerging between domestic and imported pediatric medicines.The therapeutic areas for pediatric medicines are continuously expanding,and the dosage forms are becoming more tailored to children's needs.However,there are still issues such as slow progress in new medicine development,insufficient stability in the medicine review and approval process,and a need to increase the proportion of medicines included in medical insurance.

Anxiety is a major emotional disorder manifested in the individual's expectation of future threats.The incidence rate of anxiety is about 7.3％,with the highest lifetime prevalence rate among mental health conditions.The mechanism of anxiety overlaps with depression,and anxiety is a typical symptom of various mental diseases or emotional disorders in traditional Chinese medicine.The high rates of comorbidity and disability pose serious threats to people's health.Animal models are important tools for studying anxiety and are of great use for deciphering the pathogenesis of anxiety and for developing drugs.The traditional paradigm of stress-induced anxiety,however,is relatively limited.Based on traditional theory combined with clinical and animal experimental data,we propose a new hypothesis of"insufficiency of ZhiYi'causing anxiety,defined as"an anxiety state induced by the inability of an individual to meet their own needs,limited or lacking after multiple attempts,rendered hindered and powerless by an inability to meet their desires".This hypothesis is more in line with the typical manifestations of despair,lack of pleasure,and social withdrawal in clinical patients,and is supported by traditional theory and experimental data showing"hunger but unable to eat,food but unable to obtain,and gain but not full".Based on this,the established modeling paradigm is easy to apply,with good repeatability and low cost,and can be used to establish anxiety models in rats and mice,to provide a theoretical and model basis for the development and pharmacological evaluation of anti-anxiety drugs.

Objective To use imaging features of pulmonary nodules to predict the risk of lymph node metastasis in patients with cT1-stage non-small cell lung cancer (NSCLC), providing a reference for clinical decision-making. Methods A retrospective analysis was conducted on the imaging features and postoperative pathological results of cT1 NSCLC patients who underwent surgical treatment at Linyi People’s Hospital from July 2019 to July 2022. Patients were grouped and analyzed according to lymph node metastasis status. Results A total of 1 123 patients were included, comprising 471 males and 652 females, with a median age of 59 (52, 66) years. Comparative analysis revealed that sex, age, nodule location, nodule size on imaging, solid component size, consolidation tumor ratio (CTR), average CT value, and tumor proximity to the pleura all influenced lymph node metastasis. A nomogram was constructed, indicating that the probability of lymph node metastasis in cT1 NSCLC was positively correlated with solid component size, CTR, and average CT value of the pulmonary nodule, and negatively correlated with patient age. The area under the receiver operating characteristic curve was 0.929. Conclusion For cT1 NSCLC patients, the probability of lymph node metastasis can be predicted by measuring the solid component size, CTR, and average CT value of the pulmonary nodule, in conjunction with patient age. However, relying solely on pulmonary nodule imaging characteristics is insufficient to determine a specific lymph node dissection strategy.

Objective To investigate the mechanism of Fuzheng Yangxin Prescription in improving cardiac function in rats with heart failure with reduced ejection fraction(HFrEF)through regulation of AMPK/mTOR signaling pathway.Methods An HFrEF rat model was established via left anterior descending coronary artery ligation.Rats were randomized divided into sham-operation group,model group,Fuzheng Yangxin Prescription group and Entresto group,followed by 28 days of intervention.Echocardiography was used to measure left ventricular internal dimension at end-systole(LVIDs),left ventricular internal dimension at end-diastole(LVIDd),left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),HE staining and Masson staining were used to observe myocardial morphology and fibrosis,serum contents of NT-proBNP and inflammatory factors(TNF-α,IL-1β,IL-6)were detected by ELISA,Western blot was performed to analyze p-AMPK,p-mTOR and protein expressions of autophagy markers(Beclin1,LC3,p62).Results Compared with sham-operation group,the LVIDs and LVIDd in model group significantly increased(P<0.05),while LVEF and LVFS significantly decreased(P<0.05),the structure of myocardial cells was disordered and arranged loosely,the deposition of collagen fibers in the infarct area was increased,and the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly increased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly decreased(P<0.05),while the protein expressions of p-mTOR and p62 significantly increased(P<0.05);compared with the model group,the LVIDs and LVIDd of rats in Fuzheng Yangxin Prescription group significantly decreased(P<0.05),the LVEF and LVFS were significantly increased(P<0.05),the disorder of myocardial cell arrangement and fibrosis were alleviated,the contents of NT-proBNP,TNF-α,IL-1β and IL-6 in serum significantly decreased(P<0.05),the protein expressions of p-AMPK,Beclin1 and LC3Ⅱ/LC3Ⅰ in myocardial tissue significantly increased(P<0.05),while the protein expressions of p-mTOR and p62 significantly decreased(P<0.05).Conclusion Fuzheng Yangxin Prescription may regulate autophagy by activating AMPK/mTOR pathway and improve cardiac function in HFrEF rats.

Anxiety is a major emotional disorder manifested in the individual's expectation of future threats.The incidence rate of anxiety is about 7.3％,with the highest lifetime prevalence rate among mental health conditions.The mechanism of anxiety overlaps with depression,and anxiety is a typical symptom of various mental diseases or emotional disorders in traditional Chinese medicine.The high rates of comorbidity and disability pose serious threats to people's health.Animal models are important tools for studying anxiety and are of great use for deciphering the pathogenesis of anxiety and for developing drugs.The traditional paradigm of stress-induced anxiety,however,is relatively limited.Based on traditional theory combined with clinical and animal experimental data,we propose a new hypothesis of"insufficiency of ZhiYi'causing anxiety,defined as"an anxiety state induced by the inability of an individual to meet their own needs,limited or lacking after multiple attempts,rendered hindered and powerless by an inability to meet their desires".This hypothesis is more in line with the typical manifestations of despair,lack of pleasure,and social withdrawal in clinical patients,and is supported by traditional theory and experimental data showing"hunger but unable to eat,food but unable to obtain,and gain but not full".Based on this,the established modeling paradigm is easy to apply,with good repeatability and low cost,and can be used to establish anxiety models in rats and mice,to provide a theoretical and model basis for the development and pharmacological evaluation of anti-anxiety drugs.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.

Objective To investigate the therapeutic effect and underlying mechanism of Qishishenshu Capsule on renal fibrosis in mice with early diabetic nephropathy(DN).Methods A DN mouse model was established by multiple injections of streptozotocin.The mice were randomly divided into a normal group(NC),model group(DN),and Qishi group(QS)(0.9 g/(kg·d)),with eight mice in each group.Mice were gavaged continuously for 4 weeks,and fasting blood glucose(FBG)was measured weekly.Four weeks later,urinary albumin/creatinine(UACR),serum creatinine,and blood urea nitrogen were measured.Hematoxylin-eosin,periodicacid-Schiff,and Sirius red staining were used to analyze renal pathological changes.Real-time fluorescence quantitative reverse-transcription polymerase chain reaction was used to detect the mRNA levels of fibronectin(FN),collagen type Ⅰ alpha 1(Col1a1),and α-smooth muscle actin(α-SMA).Immunohistochemistry and Western blot were performed to detect FN,collagen type Ⅰ(Collagen Ⅰ),collagen typeⅢ(Collagen Ⅲ),α-SMA,Podocin,Nephrin,and transforming growth factor-β1/SMAD family member2/3(TGF-β1/Smad2/3)pathway-related proteins.Results Compared with mice in the NC group,those in the DN group showed significantly higher levels of FBG and UACR(P＜0.001),and mesangial hyperplasia,basement membrane thickening,and collagen deposition in the renal tissue.The mRNA levels of FN,Col1a1,and α-SMA were increased(P＜0.05).Protein levels of Podocin and Nephrin were decreased(P＜0.05).The levels of FN,Collagen I,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were increased(P＜0.05).Compared with the DN group,the QS group's level of UACR was decreased(P＜0.05),their renal pathological injury was alleviated,and mRNA levels of FN,Collagen Ⅰ,andα-SMA were attenuated(P＜0.05);whereas their protein levels of Podocin and Nephrin were elevated(P＜0.05).The levels of FN,Collagen Ⅰ,Collagen Ⅲ,α-SMA,and TGF-β1/Smad2/3 pathway proteins were also decreased(P＜0.05).Conclusions Qishishenshu Capsule improved renal fibrosis in DN mice,probably through the inhibition of the TGF-β1/Smad2/3 signaling pathway.

Objective:To analyze the temporal trends of the incidence rate of tuberculosis (TB) in Shaanxi Province and provide a reference for WHO to control the prevalence of TB effectively.Methods:Joinpoint regression was used to analyze the trend of the incidence rate of TB in Shaanxi Province from 2004 to 2022, and the seasonal autoregressive moving average model was used to forecast the incidence rate of TB in Shaanxi Province to 2030.Results:The incidence rate of TB in Shaanxi Province decreased from 90.896/100 000 in 2004 to 35.364/100 000 in 2022, showing a general downward trend (AAPC=-7.72%, P<0.001). From 2014 to 2019, the reduction trend slowed down (APC=-0.69%, P=0.814), of which the largest decline occurred from 2019 to 2022 (APC=-13.26%, P=0.010). The predicted incidence rate of TB in Shaanxi Province from 2020 to 2022 was higher than the reported incidence rate, with the expected incidence rate of 51.342/100 000 in 2022 and 43.468/100 000 in 2030. Conclusion:The incidence rate of TB in Shaanxi Province shows a downward trend from 2004 to 2022, but the decline has shrunk in recent years. It is predicted that the downward trend will continue to slow down by 2030.