Predictive effect of combined procalcitonin, interleukin-6 and antithrombin III on the severity and prognosis of patients with sepsis / 中华危重病急救医学

OBJECTIVE@#To investigate the correlation of procalcitonin (PCT), interleukin-6 (IL-6) and antithrombin III (AT III) with the severity of sepsis, and to compare the predictive value of the above indicators alone or in combination.@*METHODS@#A retrospective cohort study was conducted. Eighty-five patients with sepsis admitted to the department of intensive care medicine of Shandong Provincial Hospital Affiliated to Shandong First Medical University from April 2021 to September 2022 were enrolled. General information, sequential organ failure assessment (SOFA) score and acute physiology and chronic health evaluation II (APACHE II) score within 24 hours of admission, inflammatory indicators [PCT, IL-6, serum amyloid A (SAA), neutrophil to lymphocyte ratio (NLR), and C-reactive protein (CRP)] and coagulation indicators (D-dimer and AT III) levels at admission, and 28-day prognosis were collected. The differences of the above indicators were compared among patients with different prognosis at 28 days and different severity of sepsis. The correlation between PCT, IL-6, AT III and the severity of sepsis was analyzed by Spearman rank correlation method. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of PCT, IL-6 and AT III alone or in combination on the 28-day death of patients with sepsis.@*RESULTS@#Eighty-five patients were enrolled finally, 67 cases survived and 18 cases died at 28 days. The mortality was 21.2%. There were no statistical significant differences in gender, age and other general data between the two groups. The patients in the death group were more serious than those in the survival group, and PCT, IL-6, and CRP levels were significantly higher than those in the survival group [PCT (μg/L): 4.34 (1.99, 14.42) vs. 1.17 (0.31, 3.94), IL-6 (ng/L): 332.40 (50.08, 590.18) vs. 61.95 (31.64, 194.20), CRP (mg/L): 149.28 (75.34, 218.60) vs. 83.23 (48.22, 174.96), all P < 0.05], and AT III activity was significantly lower than that in the survival group [(53.67±28.57)% vs. (80.96±24.18)%, P < 0.01]. However, there were no significant differences in D-dimer, NLR and SAA between the two groups. Among the 85 patients, 36 had sepsis with single organ dysfunction, 29 had sepsis with multiple organ dysfunction, and 20 had septic shock with multiple organ dysfunction. With the increase of the severity of sepsis, PCT and IL-6 levels gradually increased [PCT (μg/L): 0.36 (0.19, 1.10), 3.00 (1.22, 9.94), 4.34 (2.18, 8.86); IL-6 (ng/L): 43.99 (20.73, 111.13), 100.00 (45.37, 273.00), 332.40 (124.4, 693.65)], and the activity of AT III decreased gradually [(89.81±21.42)%, (71.97±24.88)%, and (53.50±25.41)%], all with statistically significant differences (all P < 0.01). Spearman rank correlation analysis showed that PCT and IL-6 levels in sepsis patients were significantly positively correlated with the severity of the disease (r values were 0.562 and 0.517, respectively, both P < 0.01), and AT III activity was significantly negatively correlated with the severity of the disease (r = -0.523, P < 0.01). ROC curve analysis showed that PCT, IL-6, and AT III alone or in combination had some predictive value for the death of sepsis patients at 28 days. The area under the ROC curve (AUC) of the above three indicators in combination was higher than that of the individual tests (0.818 vs. 0.722, 0.725, and 0.770), with a sensitivity of 83.3% and a specificity of 73.1%.@*CONCLUSIONS@#PCT, IL-6, and AT III were significantly correlated with the severity of sepsis patients. The combined assay of the above three indicators can effectively improve the prediction of the prognosis of sepsis patients.

Molecular Mechanism Analysis of Dengzhan Shengmai Capsules Against Chronic Cerebral Hypoperfusion / 中国实验方剂学杂志

ObjectiveBased on the protective effect of Dengzhan Shengmai capsules （DZSM） on chronic cerebral hypoperfusion （CCH）， network pharmacology was employed to investigate the molecular mechanism. MethodCCH model was established by right common carotid artery ligation. The mice were divided into sham operation group， model group， ginaton group （48 mg·kg-1）， DZSM low- and high-dose groups （0.040 5， 0.162 g·kg-1）. The efficacy was evaluated by the Morris water maze test and open-field test. The underlying mechanism of DZSM for CCH was analyzed by network pharmacology and verified by molecular biology experiments. PubChem， GeneCards， Metascape and other databases were used for targets collection and enrichment analysis. Besides， the association of ingredients targets of DZSM with disease targets of CCH， core target network and chemical components-core targets-pathways network were constructed by STRING 11.0 and Cytoscape 3.7.1. ResultThe escape latency of CCH mice significantly shortened on the 3rd to 5th day after DZSM low-dose treatment， the crossing times， time spent in the target quadrant， movement distance and distance in the central region of CCH mice significantly increased after DZSM low-dose and high-dose treatment. The results of network pharmacology indicated that DZSM might play a key role by regulating inflammatory response， phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway， cytokine-cytokine receptor interaction， tumor necrosis factor （TNF） signaling pathway， blood circulation， angiogenesis， extracellular matrix and other related biological processes and pathways， and acting as targets such as interleukin-6 （IL-6）， TNF， insulin-like growth factor 1 （IGF1）， vascular endothelial growth factor A （VEGFA）， epidermal growth factor （EGF）. The results of biological experiments showed that DZSM could reduce the expression of IL-6 in brain tissue of CCH mice. ConclusionDZSM provides a protective effect during CCH， and its multi-component， multi-pathway， multi-target mechanism is also revealed， which provides a basis for further study of the mechanism.

Research Status and Comparison on Medicinal Plants of Callerya and Millettia in China / 中国实验方剂学杂志

The Leguminosae perennial vines of Callerya and Millettia have many species and wide distribution， not only can be used for medicines， but also they have ornamental and insecticidal effects. With increasing demand for Spatholobi Caulis， and the reserves of wild medicinal materials are on the verge of exhaustion， resulting in the increasing number of mixtures and substitutes in the market， which makes it urgent to study the origin of Spatholobi Caulis. By referring to related literature， there are three major origins of Spatholobi Caulis， including Callerya， Millettia and Spatholobus. Callerya is separated from Millettia， they are divided and united for many times， now the official website of Flora of China has accepted the revision of them as two genera. This paper intends to compare the chemical components and pharmacodynamic effects of Callerya and Millettia， aiming to explore the similarities and differences between the two genera， so as to determine the rationality and necessity of separating Callerya from Millettia. After comparing， it was found that the chemical composition and pharmacodynamic effects of the two genera were different， which supported the separation of Callerya from Millettia， and it was not recommended to mix use of them.

T790M mutation is associated with better efficacy of treatment beyond progression with EGFR-TKI in advanced NSCLC patients.

BACKGROUND AND PURPOSE: Continuous EGFR-TKI treatment beyond progression has shown promising benefit for some patients with acquired resistance to EGFR-TKIs. The aim of this study was to investigate the association of secondary T790M mutation at the time of progression with the efficacy of EGFR-TKI treatment beyond progression. METHODS: From March 2011 to March 2013, patients with advanced NSCLC who developed acquired resistance to EGFR-TKI and where a re-biopsy was performed at Tongji University Cancer Institute were included into this study. Scorpion ARMS was used to detect EGFR mutation status. RESULTS: A total of 54 patients were enrolled in this study with a median progression-free survival time (PFS1) of 10.9 months according to RECIST criteria. In all, 53.7% (29/54) had T790M mutation after the failure of EGFR-TKIs; PFS1 was not statistically significantly different between patients with T790M mutation and without (13.0 vs. 10.5 months, p = 0.894). In all, 41 patients received TKI treatment beyond progression, including 22 with local progression to receive additional local therapy and 19 with gradual progression to receive additional chemotherapy. The median progression-free survival time (PFS2) of patients who received EGFR-TKI beyond progression treatment was 3.5 months (95% CI, 2.689-4.311). Patients with T790M mutation had significantly longer PFS2 (6.3 vs. 2.6 months, p = 0.002) and overall survival (39.8 vs. 23.2 months, p = 0.044) than those without. CONCLUSION: Patients with secondary T790M mutation at the time of progression having gradual or local progression after acquired resistance to EGFR-TKI benefit more from EGFR-TKI treatment beyond progression compared to those without T790M mutation.

Epithelial phenotype as a predictive marker for response to EGFR-TKIs in non-small cell lung cancer patients with wild-type EGFR.

Epithelial-to-mesenchymal transition (EMT) has profound impacts on cancer progression and also on drug resistance, including epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Nowadays, there is still no predictive biomarker identified for the use of EGFR-TKIs in non-small cell lung cancer (NSCLC) patients with wild-type EGFR. To clarify the role of EMT phenotype as a predictive marker for EGFR-TKI, we performed a retrospective study in 202 stage IV or recurrent NSCLC patients receiving gefitinib or erlotinib therapy from June 2008 to September 2012 in our institute. Clinical data and EGFR mutational status were collected, while epithelial, epithelial to mesenchymal, not specified or mesenchymal phenotype were classified according to EMT markers such as E-cadherin, fibronectin, N-cadherin and vimentin by immunohistochemistry. Epithelial phenotype was more frequently found in patients with EGFR mutation (p = 0.044). Epithelial phenotype was associated with a significantly higher objective response rate (23.5 vs. 11.1 vs. 0.0 vs. 2.4%, p = 0.011), longer progression-free survival (4.4 vs. 1.9 vs. 1.7 vs. 1.0 months, p < 0.001) and longer overall survival (11.5 vs. 8.9 vs. 4.5 vs. 4.9 months, p < 0.001) compared to epithelial to mesenchymal, not specified and mesenchymal phenotype in the wild-type EGFR subgroup. In the subgroup with EGFR mutation, the trend remained but without a statistically significant difference. In conclusion, epithelial phenotype was more likely expressed in patients with EGFR mutation and was associated with a better outcome in advanced NSCLC patients with wild-type EGFR, which indicates that the EMT phenotype might be a potential marker to guide EGFR-TKI therapy in this population.

Acellular tissue matrix mesh for inguinal herniopasty / 中华普通外科杂志

Objective To evaluate acellular tissue matrix mesh in inguinal hernioplasty in young male patients.Methods Clinical outcome and sexual function were evaluated on 12 young male inguinal hernia patients undergoing inguinal hernioplasty by ACTM mesh.Results The mean operation time was 62 minutes.Postoperative analgesics were needed for an average of 1.45 days (range,0 -4 days).The average postoperative hospital stay was 3.9 days,and patients were able to return to normal activity,after a mean 11.8 days.All patients were followed-up for a mean duration of 9.54 months(range,6 - 16 months).Two patients complained pain one month after surgery and the pain disappeared later without any medical treatment.There was no hernia recurrence and foreign body feelings,nor sexual and reproductive problems.Conclusions The ACTM mesh is a safe and effective material for inguinal hernioplasty,especially in young male patients.