ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

ObjectiveThis paper aims to find the identified and validated clinical biomarker data building upon a clinical study of early-phase phase Ⅱ and investigate the correlation analysis of Huanglian Jiedu Wan on syndrome improvement and clinical biomarkers in the treatment of "excess heat-toxicity" based on a machine learning model. Additionally， the effective prediction of clinical biomarker values for the main symptoms of the "excess heat-toxicity" syndrome was assessed. MethodsA total of 229 patients meeting the inclusion criteria for "excess heat-toxicity" syndrome were randomly divided into the Huanglian Jiedu Wan group and the placebo group. Syndrome score transition matrices were constructed for the Huanglian Jiedu Wan group and the placebo group based on three main symptoms of "excess heat-toxicity" syndrome， such as oral ulcers， sore throat， and gum swelling and pain. Data from the patients with these three syndromes were also integrated for an overall analysis. The corresponding syndrome score transition matrices were further constructed to visualize symptom change trends of the patients in the two groups via heatmaps. Based on the identified and validated clinical biomarkers related to inflammation， oxidative stress， and energy metabolism in the early phase， Spearman correlation analysis was employed to analyze and evaluate the associations between clinical biomarkers and syndrome improvement. Key clinical biomarkers reflecting the effect of Huanglian Jiedu Wan were screened through the comparison of differences between groups. An extreme gradient boosting （XGBoost） algorithm was used to develop a prediction model for main symptom classification， with classification performance evaluated through 10-fold cross-validation. Feature importance analysis was applied to identify variables with the greatest contribution to the prediction result. ResultsThe syndrome transition matrix results indicated that the Huanglian Jiedu Wan group showed a superior effect to the placebo group in improving oral ulcers， sore throat， and overall symptoms， with significant effects observed especially in sore throat and overall symptom analyses （P<0.01）. Spearman correlation analysis revealed that several clinical biomarkers positively correlated with "excess heat-toxicity" syndrome and its main symptom improvement， were also called "heat-related biomarkers"， including succinic acid， α-ketoglutaric acid， glycine， lactic acid， adenosine monophosphate （AMP）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， interleukin-1β （IL-1β）， interleukin-4 （IL-4）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， interleukin-10 （IL-10）， and so on. Conversely， clinical biomarkers negatively correlated with symptom severity， were also called "heat-clearing related biomarkers" after administration of Huanglian Jiedu Wan， including malic acid， fumaric acid， cis-aconitic acid， adrenocorticotropic hormone （ACTH）， IL-1β， IL-4， IL-8， succinic acid， and citric acid. The XGBoost classification model using all 52 biomarkers as variables achieved an average test accuracy of 0.754 and an average F1 score of 0.777. Feature importance analysis identified the scores of glutamic acid in saliva and IL-6 were the highest in all the variables， with importance scores of 0.081 and 0.080， respectively. After screening out 14 key variables and optimizing the parameters， model performance improved to an average accuracy of 0.758 and an F1 score of 0.798. Feature importance analysis further determined that the glutamic acid in saliva and IL-6 showed obvious changes after screening the variables， confirming the good syndrome prediction ability of the model constructed by these key clinical biomarkers. ConclusionThis study systematically elucidates the correlation between syndrome improvement and clinical biomarkers of Huanglian Jiedu Wan in the treatment of "excess heat-toxicity" syndrome. An XGBoost classification model based on key clinical biomarkers is successfully established， achieving effective prediction of the symptoms related to the "excess heat-toxicity" syndrome such as oral ulcers and sore throat and providing a new insight for objective identification of traditional Chinese medicine syndromes.

OBJECTIVE To investigate the effects of osthole （OST） on skin wound healing and angiogenesis in rats by regulating the sonic hedgehog （SHH） signaling pathway. METHODS Full-layer skin defect wound model rats were established and then randomly separated into Model group， OST low-dose， medium-dose and high-dose groups （OST-L group， OST-M group， OST-H group， 20， 30， 40 mg/kg OST）， high-dose OST+SHH inhibitor cyclopamide group （OST-H+cyclopamide group， 40 mg/kg OST+10 mg/kg cyclopamide）， with 12 rats in each group. Another 12 rats were selected as the control group. The wound healing of rats on 1， 7 and 14 days of administration was observed， and the wound healing rate of rats in each group was measured. The pathological changes and collagen deposition in rat wound tissue were observed； the levels of angiopoietin-1 （Ang-1） and basic fibroblast growth factor （bFGF） in wound tissue of rats were detected； the relative expressions of vascular endothelial growth factor A （VEGFA） and vascular endothelial growth factor receptor-2 （VEGFR-2） mRNA were also detected in wound tissue of rats； the protein expressions of VEGFA， VEGFR-2， SHH and glioma-associated oncogene homolog-1 （GLI1） were determined in wound tissue of rats. RESULTS Compared with Model group， the healing rate of skin wound， relative expression of collagen protein， the levels of Ang-1 and bFGF， the mRNA and protein expressions of VEGFA and VEGFR-2， and the protein expressions of SHH and GLI1 were all significantly increased in OST-M and OST-H groups （P＜0.05）. The wound tissue underwent significant re- epithelialization， with reduced inflammatory cell infiltration and granulation tissue edema， and an increase in the number of new blood vessels. SHH inhibitor cycloparamide weakened the promoting effects of OST on skin wound healing and angiogenesis in rats. CONCLUSIONS OST may promote skin wound healing and angiogenesis in rats by activating the SHH signaling pathway.

“Inflammation-cancer” transformation of chronic atrophic gastritis （CAG） refers to the process in which the gastric mucosa， in the context of CAG， progresses through stages of precancerous lesions of gastric cancer （PLGC）， such as intestinal metaplasia and dysplasia， and eventually develops into gastric cancer （GC）. In China， the incidence and mortality rates of GC rank among the highest in the world， and the proportion of GC cases caused by gastric mucosal infection and inflammation has been increasing. Modern medical treatments for CAG and PLGC mainly rely on drug therapy， endoscopic resection， and regular surveillance. Although these disease management strategies are relatively mature， they present limitations in early lesion prevention and recurrence risk control. Therefore， it is imperative to identify therapeutic approaches for CAG and PLGC that offer preventive， reversible， and recurrence-reducing benefits. With advances in research on the mechanisms underlying inflammation-cancer transformation and the integration of traditional Chinese and Western medicine， the advantages of TCM in preventing and even reversing early-stage CAG and PLGC have gradually become apparent. This review explored the mechanisms of inflammation-cancer transformation in CAG from five aspects： inflammatory microenvironment， autophagy， glycolysis， bile acids， and ferroptosis. In conjunction with TCM theory and a deeper understanding of the distinct mechanisms involved in the inflammation-cancer transformation of CAG， this review further discussed the specific mechanisms through which TCM intervened in treating CAG and PLGC， with the aim of providing theoretical support and therapeutic insights for future clinical applications.

“Inflammation-cancer” transformation of chronic atrophic gastritis （CAG） refers to the process in which the gastric mucosa， in the context of CAG， progresses through stages of precancerous lesions of gastric cancer （PLGC）， such as intestinal metaplasia and dysplasia， and eventually develops into gastric cancer （GC）. In China， the incidence and mortality rates of GC rank among the highest in the world， and the proportion of GC cases caused by gastric mucosal infection and inflammation has been increasing. Modern medical treatments for CAG and PLGC mainly rely on drug therapy， endoscopic resection， and regular surveillance. Although these disease management strategies are relatively mature， they present limitations in early lesion prevention and recurrence risk control. Therefore， it is imperative to identify therapeutic approaches for CAG and PLGC that offer preventive， reversible， and recurrence-reducing benefits. With advances in research on the mechanisms underlying inflammation-cancer transformation and the integration of traditional Chinese and Western medicine， the advantages of TCM in preventing and even reversing early-stage CAG and PLGC have gradually become apparent. This review explored the mechanisms of inflammation-cancer transformation in CAG from five aspects： inflammatory microenvironment， autophagy， glycolysis， bile acids， and ferroptosis. In conjunction with TCM theory and a deeper understanding of the distinct mechanisms involved in the inflammation-cancer transformation of CAG， this review further discussed the specific mechanisms through which TCM intervened in treating CAG and PLGC， with the aim of providing theoretical support and therapeutic insights for future clinical applications.

[Abstract] [Objective] To assess the effect of a centrifugal haemocyte separator on platelet counts in patients with neurological immune-mediated disorders during/after therapeutic plasma exchange (TPE). [Methods] This study included 189 patients (108 females and 81 males) who were treated in the department of neurology at Huashan Hospital, Fudan University, from March 2021 to March 2022. A total of 820 TPE treatments were carried out. Each patient received 2 to 5 TPEs, with each TPE amounting to the patient's plasma volume. The peripheral blood cell counts of the patients were evaluated before TPE and after 2 to 5 TPEs. [Results] The duration of a single TPE in this study was 94(84,107) minutes, and the actual volume of a single TPE replacement was 2 456(2 142, 2 785) mL. The number of patients who underwent TPE for 2, 3, 4, and 5 sessions was 17, 28, 18, and 126, respectively. The platelet (PLT) counts of the patients before and after the TPE were 195×10⁹/L (range:150 to 245) and 220×10⁹/L (range:170 to 270), respectively (P<0.05). Consequently, the overall PLT counts exhibited a significant decrease from baseline following TPE, yet the PLT counts remained within the normal range after TPE. Spearman's correlation analysis indicated that platelet loss did not correlate with the duration of TPE (ρ=0.037), the age of the patient (ρ=0.015), or the volume of the single replacement fluid (ρ=0.034), P>0.05, weakly correlated with the number of TPE sessions (ρ=0.017), and moderately correlated with the PLT counts before TPEs (ρ=0.446). [Conclusion] The TPE procedure exhibited a measurable impact on the patients' platelet levels, but the platelet counts remained within the normal range, therefore did not interfere with the patients' subsequent treatment protocols. The decrease in platelet level was correlated with the baseline platelet level before treatment and the number of TPE sessions.

Objective Nowadays, radioactive xenon isotopes, including ^131mXe, ^133mXe, ¹³³Xe, and ¹³⁵Xe, are primarily released into the atmosphere through various reactor operation and major accidents of reactors. To improve the online monitoring capability of xenon in nuclear facilities and their gaseous effluents, a highly sensitive online xenon monitoring system was developed to monitor, warn, and alarm the activity concentration of radioactive xenon. Methods The online monitoring system for radioactive xenon gas in nuclear facilities was established using xenon membrane separation and concentration, xenon high-efficiency selective adsorption, and low-background gamma-ray spectrometry analysis methods. Results Under the operation mode of one-hour sampling and one-hour measuring, the minimum detectable activity concentration of the radioactive xenon online monitoring system for ¹³³Xe was approximately (1.43 ± 0.03) Bq/m³. Conclusion This system can be effectively used for online monitoring of xenon activity concentration in nuclear facilities such as nuclear power plants and isotope production reactors, as well as in gaseous effluents. It helps improve the safety level of personnel, the environment, and nuclear facilities.

Objective:To investigate the epidemiology features, intervention effects and influencing factors of thrombosis in arteriovenous graft (AVG), and to provide reference for optimizing vascular access scheme in hemodialysis patients.Methods:It was a retrospective study. The clinical and follow-up data of patients with AVG constructed in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were analyzed. According to whether AVG thrombosis occurred during the follow-up period, they were divided into thrombosis group and non-thrombosis group, and the epidemiology status, influencing factors and patency rates of AVG thrombosis were analyzed. AVG was followed up until June 30, 2023 or abandonment or death of patient or loss of follow-up. Kaplan-Meier method was used to analyze the patency rates of AVG. Log-rank test was used to compare the differences of patency rates between groups. Logistic regression model was used to analyze the influencing factors of AVG thrombosis.Results:The study included 475 AVG from 464 patients, with age of (55.50 ± 11.85) years old, 193 males (40.6%), 185 diabetes patients (38.9%) and dialysis age of 24 (1, 68) months. One hundred and fifty-four AVG (32.4%) had a total of 307 AVG thrombotic events during the follow-up of 602 (380, 920) days, with a standardized incidence of 0.34 times per patient-year. Among them, 60 cases (19.5%, 60/307) had frequent thrombosis. Kaplan-Meier survival analysis showed that AVG secondary patency rates at 2-years and 3-years in the thrombosis group and frequent thrombosis subgroup were inferior to those in the non-thrombosis group (84.0% vs. 92.5%, P=0.017; 66.5% vs. 85.7%, P<0.001; 78.9% vs. 92.5%, P=0.030; 54.6% vs. 85.7%, P<0.001). Two hundred and sixty-nine AVG thrombotic events were analyzed to evaluate the treatment effects. Endovascular interventional surgery was used for thrombectomy in 215 cases (79.9%), and hybrid surgery (endovascular interventional surgery combined with surgical incision) was used in 54 cases (20.1%), with a technical success rate of 98.9% (266/269) and a clinical success rate of 98.1% (264/269). Kaplan-Meier survival analysis showed that there were no statistically significant differences in the primary post-intervention patency rates at 90 days and 365 days, respectively (all P>0.05), and there was statistically significant difference in the primary post-intervention patency rate at 180 days (45.1% vs. 26.5%, Z=2.563, P=0.015). Multivariate logistic regression analysis showed that graft-applied type (intering as the reference, propaten OR=1.953, 95% CI 1.139-3.350, P=0.015; acuseal OR=2.628, 95% CI 1.438-4.800, P=0.002), body mass index < 18.5 kg/m 2 (18.5-24.0 kg/m 2 as the reference, OR=0.291,95% CI 0.090-0.943, P=0.040), serum albumin < 40 g/L ( OR=1.579, 95% CI 1.019-2.445, P=0.041), serum ferritin < 200 μg/L ( OR=1.818, 95% CI 1.162-2.845, P=0.009) and mean arterial pressure < 70 mmHg ( OR=7.180, 95% CI 1.339-38.501, P=0.021) were the independent influencing factors of AVG thrombosis. Conclusions:The incidence of AVG thrombotic events is 0.34 times per patient-year, mainly concentrated in a small number of patients. Thrombosis reduces the secondary patency rate of AVG. AVG thrombosis treatment with endovascular interventional surgery or hybrid surgery has a high technical success rate and a clinical success rate. The thrombosis is related to graft-applied types, nutritional status of patients and mean arterial pressure level.

Objective:To investigate the clinical outcomes of hemodialysis (HD) patients with stent grafts for arteriovenous access complications in real-world.Methods:It was a retrospective cohort study. Clinical data of HD patients treated with stent grafts for arteriovenous access complications from August 1, 2018 to December 31, 2021 in the First Affiliated Hospital of Zhengzhou University was collected to analyze target lesion primary patency (TLPP), target lesion primary assisted patency (TLPAP), and access circuit primary patency (ACPP) using the Kaplan-Meier survival analysis and Log-rank test, and to compare TLPP and mean annual intervention times between pre-stent grafts and post-stent grafts placement.Results:A total of 77 stent grafts in 71 patients were included according to the inclusion criteria, of which 46 (59.7%) were arteriovenous fistula (AVF) and 31 (40.3%) were arteriovenous graft (AVG), with a median follow-up time of 22.4 months. At 6, 12, 24, and 36 months after stent grafts deployment, TLPP was 89.3%, 66.5%, 48.3% and 42.5%, respectively. TLPAP was 94.8%, 90.4%, 78.7% and 75.4%, respectively. And ACPP was 77.2%, 54.3%, 35.2% and 29.0%, respectively. At subgroup analysis, there was no difference in TLPP at the three different sites of central vein, cephalic arch, and AVG venous anastomosis or outflow tract ( χ2=0.086, P=0.808). TLPP was better in the stenosis group than thrombosis or occlusion group, but was not statistically significant ( χ2=2.551, P=0.110). Compared with pre-stent grafts, TLPP improved significantly ( χ2=7.484, P=0.006), the median patency time increased from 16.6 months to 23.2 months, and the mean annual intervention times decreased from 0.99 (0.10, 1.83) to 0.50 (0, 1.45) ( Z=-2.841, P=0.004) after stent grafts placement Conclusion:The TLPP of HD patients with stent grafts for arteriovenous access complications improves significantly, and the mean annual intervention times reduce significantly.

OBJECTIVE To study the correlation between color and inner quality during the processing of Prunus mume carbon， and provide reference for the determination of processing end point of P. mume carbon. METHODS The chromaticity value of P. mume carbon powder was measured by colorimeter， and the inner quality of P. mume carbon was measured by selecting the contents of water， water-soluble extract， citric acid and tannin. The dynamic change trend of the chromaticity value， water， water- soluble extract， the contents of citric acid and tannin in P. mume carbon under different processing time was analyzed. The correlation between color and the above indexe contents was analyzed， and the regression equation of inner quality-chromaticity value was established. Combined with principal component analysis （PCA）， hierarchical cluster analysis （CA） and partial least squares discriminant analysis （PLS-DA）， the difference of P. mume carbon at different processing times was analyzed to determine the processing end point. RESULTS With the extension of processing time， the sample color gradually deepened； the chromaticity values L* and E* of the samples increased at first and then decreased， the chromaticity values a* and b* decreased， and finally all tended to be stable. The content of water-soluble extract， citric acid and tannin in the sample increased at first and then decreased， the water content of the sample decreased with time and finally stabilized. Correlation analysis showed that water， water-soluble extract， citric acid and tannin were positively correlated with L*， a*， b* and E*（P＜0.001）. PCA and HCA showed that P. mume carbon under different processing time could be clustered into two categories： the processed samples of 0-30 min and those of 40-60 min. PLS-DA showed that water and water-soluble extract were important quality indexes and b* was an important chrominance index in the processing of P. mume carbon. The chromaticity value of the samples processed for 50 min and 60 min were not significantly different. The contents of water， water- soluble extract， citric acid and tannin in the samples processed for 60 min were less than those processed for 50 min. CONCLUSIONS There is a certain correlation between the color and the inner quality of P. mume carbon. The processing time of P. mume carbon should be 40-50 min.