Objective To compare the diagnostic performance of a multi-marker panel(copeptin,cardiac troponin T[cTnT],and heart-type fatty acid-binding protein[HFABP])with the single marker cTnT in the diagnosis of type 4a acute myocardial infarction(AMI),and explore the application value of combined detectionmodel with the multiple markers.Methods The enrolled non-AMI pa-tients underwent elective percutaneous coronary intervention(PCI)at Nanjing Medical University First Affiliated Hospital during the period from March to December 2022 and were assessed as postoperative elevation of cTnT above the 99th percentile upper reference limit(URL).According to the Fourth Universal Definition of Myocardial Infarction,the patients were divided into non-type 4a AMI group and type 4a AMI group based on whether type 4a AMI occurred after surgery.The concentrations of AMI biomarkers were meas-ured using a chemiluminescent immuno-gold nanoassembly immunosensor array(chemiluminescent immuno-Gold,ciGold).Receiver operating characteristic(ROC)curves were used to analyze the performance of the diagnostic models with single and combined cardiac biomarkers.The sensitivity and specificity were also obtained from the ROC curves,and the area under the ROC curve(AUCROC)was calculated to evaluate respective diagnostic value.Kappa analysis was used to assess the consistency between the results combined de-tection model of multiple biomarkers and the diagnosis based on the Fourth Universal Definition of Myocardial Infarction.Results In this study,a total of 65 patients were included in whom females accounted for 23.1％.The ROC curve indicated that the combined de-tection model of multiple cardiac biomarkers showed specificity of 96.5％,sensitivity of 92.3％,agreement rate of 94.6％,positive pre-dictive value of 92.3％,negative predictive value of 96.2％,and AUCROC of 0.979.The single cTnT diagnostic model showed specificity of 94.2％,sensitivity of 100％,agreement rate of 95.7％,positive predictive value of 100％,negative predictive value of 94.9％,and AUCROC of 0.987.Although the combined detection model of multiple biomarkers had lower sensitivity(P=0.011),it showed higher specificity(P=0.016).The analysis of AUCROC differences between the two diagnostic models showed P＞0.05,indicating no signifi-cantly statistical difference for the diagnostic accuracy.Kappa analysis demonstrated a strong consistency between the combined detec-tion model of multiple cardiac biomarkers and the diagnosis of type 4a AMI based on the Fourth Universal Definition of Myocardial In-farction with a Cohen's Kappa coefficient of 0.818.Conclusion The multi-marker combined detection model showed similar perform-ance of cTnT in diagnos of type 4a AMI with strong diagnostic consistency.However,the combined detection model exhibited an advan-tage of higher specificity.

Langerhans cell histiocytosis (LCH) is a rare disease characterized by the proliferation of Langerhans cells and the destruction of local tissue. LCH large occurs in children, whilst incidence of the elderly population is extremely low, and there are few related studies. LCH lesions can involve multiple organs and systems, including bone tissue, lymph nodes, skin, liver, and spleen. However, it is rare that multiple soft tissues are implicated for eldly patients with LCH and present with soft tissue mass as the main manifestation. Here is a report on the clinical features, treatment and prognosis of an elderly LCH with multiple soft tissue masses as the main manifestation, in order to provide clinical reference.

ObjectiveTo explore the effect and toxicity change rule of Aconiti Lateralis Radix Praeparata（ALRP） and Zingiberis Rhizoma（ZR） before and after compatibility， and to reveal the compatibility connotation of them. MethodSixty SD rats were randomly divided into blank group， blank-ALRP group， blank-ALRP-ZR group， model group， model-ALRP group and model-ALRP-ZR group， the latter three groups were injected with adriamycin via tail vein to establish the model of heart failure， and the former three groups were injected with the same amount of physiological saline via tail vein. The effects of ALRP single decoction and ALRP-ZR mixed decoction on biochemical indexes and myocardial histopathological morphology of normal rats and model rats were compared. Metabolomics analysis was performed on rat serum samples， principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were used to screen the differential metabolites between groups， and the differential metabolic pathways were analyzed. Combined with network pharmacology technology， the metabolites and their associated targets and pathways related to enhancing anti-heart failure efficacy and reducing cardiotoxicity were screened before and after the compatibility of ALRP and ZR， the screened representative pathways were verified by Western blot. ResultCompared with the blank group， the model group showed significant increases in the contents of brain natriuretic peptide（BNP）， creatine kinase（CK）， lactate dehydrogenase（LDH） and cardiac troponin（cTn）-T（P<0.01）， the blank-ALRP group showed obvious increases in CK， LDH， and cTn-T contents（P<0.05， P<0.01）， while the normal-ALRP-ZR group showed a significant increase in CK content（P<0.01）. Compared with the blank-ALRP group， the blank-ALRP-ZR group showed a obvious decrease in LDH content（P<0.05）， and pathological sections showed that both decoctions could lead to myocardial histopathological damage in normal rats. Compared with the model group， the model-ALRP-ZR group showed obvious decreases in BNP， CK， LDH and cTn-T contents（P<0.05， P<0.01）， and the model-ALRP group showed obvious decreases in BNP， LDH and cTn-T contents（P<0.05， P<0.01）. Compared with the model-ALRP group， the model-ALRP-ZR group showed a significant decrease in CK content（P<0.01）， and both decoctions could improve the pathological morphology of myocardial tissue in the model rats. Metabolomics results showed that ALRP single decoction and ALRP-ZR mixed decoction could recover 422 and 459 metabolites in model rats， respectively. And the metabolic disruption of ALRP-ZR mixed decoction on normal rats was weaker than that of ALRP single decoction. The results of network pharmacological association analysis showed that in the aspect of ZR enhancing the anti-heart failure efficacy of ALRP， 3 metabolites such as deoxyuridylic acid were correlated to 56 metabolites， 82 targets and 13 pathways， including calcium signaling pathway， renin secretion， renin-angiotensin system， etc. In the aspect of ZR reducing the cardiotoxicity of ALRP， 3 metabolites such as tyrosol were associated with 24 metabolites， 55 targets and 14 pathways， including adrenergic signaling in cardiomyocytes and carbon metabolism and so on. Western blot results showed that the expression of angiotensin-converting enzyme（ACE）， angiotensin-converting enzyme 2（ACE2） and angiotensin Ⅱ（Ang Ⅱ） in myocardial tissues of rats from the model group was significantly elevated by comparing with the blank group（P<0.01）. Compared with the model group， the model-ALRP group and the model-ALRP-ZR group showed significantly decreased expression of ACE， ACE2 and Ang Ⅱ（P<0.01）. Compared with the model-ALRP group， the expression of ACE2 and AngⅡ was significantly decreased in the model-ALRP-ZR group. Compared with the blank group， the expression of extracellular signal regulated kinase（ERK）， protein kinase B（Akt） and cTn-I3 was significantly elevated in the blank-ALRP group and blank-ALRP-ZR group（P<0.01）. Compared with the blank-ALRP group， the blank-ALRP-ZR group showed decreased expression of ERK， Akt and cTn-I3， but there was no statistical significance. ConclusionTo a certain extent， the combination of ALRP and ZR shows synergistic relationship under pathological state， and attenuated effect of compatibility under normal physiological state， and the pharmacodynamic characteristics and compatibility relationship of ALRP and ZR are closely related to the physiological state.

Objective:To optimize the extraction process of Shangke Huoxue Granule.Methods:Taking the factors of extraction solvent multiple, extraction time and extraction times as investigation factors, and extraction amount of ferulic acid, paeoniflorin and the ratio of extraction as comprehensive evaluation indices, one-factor experimental design and central composite design-response surface methodology were adopted to optimize the extraction process of Shangke Huoxue Granule.Results:The binomial fitting equation was Y=96.16+2.42 A+0.63 B-3.76 AB-1.57 A2-1.87 B2 ( P<0.01). The optimal extraction process parameters were confirmed to be adding 16 times of water, 64 minutes each time, twice. The deviation rates between the measured values of three verification experiments and the predicted value were 2.00%, 3.23% and 0.66%. Conclusion:The established model of central composite design-response surface methodology has high predictability and the optimized extraction process is stable and feasible.

Myeloproliferative neoplasms (MPN) are a group of clonal disorders of hematopoietic stem cells, and JAK2 V617F gene mutation is the main basis for the diagnosis of MPN. Previous studies have shown that BCR-ABL fusion gene and JAK2 V617F gene mutation are mutually exclusive in MPN patients, but in recent years, patients with a double mutation of both genes are often reported. The article synthesizes the relevant domestic and foreign literature in recent years, and reviews the BCR-ABL fusion gene and JAK2 V617F mutation double-positive MPN.

Objective:To establish the TLC identification method and content determination method of ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin in Shangke Huoxue Decoction for quality evaluation.Methods:Ferulic acid, ligustilide, hydroxysafflor yellow A and paeoniflorin were qualitatively identified by TLC method, and the content was determined by HPLC method. Waters Symmetry ShieldTM RP18 column (4.6 mm×250 mm, 5 μm) was set, the mobile phase consisted of acetonitrile-0.15% phosphoric acid water with gradient elution at a flow of 1.0 ml/min, and the column temperature was 30 ℃.The detection wavelength was 320 nm (33-50 min for ferulic acid, 55-70 min for ligustilide), 403 nm (7-31 min for hydroxysafflor yellow A) and 230 nm (7-31 min for paeoniflorin).Results:The TLC spots were clear. The linear relationships of ferulic acid, ligustilide, and hydroxysafflor yellow A were good in the range of 3.05-48.74 μg, 3.50-26.24 μg, 21.34-213.44 μg. The method was stable, repeatable with good recovery rate.Conclusion:The TLC and HPLC method for the simutanous determination of the four effective components in Shangke Huoxue Decoction were established, and the methods are suitable for the quality evaluation of Shangke Huoxue Decoction.

Objective:To investigate the clinical characteristics of de novo malignancies (DNMs) after liver transplantation (LT) and to study the clinical management strategies.Methods:Adult LT recipients who were regularly followed-up in the Organ Transplantation Center, the Affiliated Hospital of Qingdao University from January 2005 to April 2021 were enrolled in this study. The clinical characteristics of DNMs were retrospectively analyzed. Of 601 LT recipients, there were 105 females and 496 males, aged (51.4±9.6) years old. They were divided into the DNMs group ( n=26) and the non-DNMs group ( n=575) according to whether there were DNMs on followed-up. Clinical data including age, sex, basic diseases before LT and operation time were collected. These patients were follow-up in outpatient clinics. Results:Twenty-six patients were diagnosed to develop DNMs after LT, but there were 28 DNMs (of which 2 patients were diagnosed to have DNMs twice). The incidence of DNMs after LT was 4.3% (26/601), the median time from LT to DNMs was 42 (20, 70) months, and the cumulative incidence rates of DNMs were 0.5%, 2.0%, 6.3%, 21.0% and 34.5% at 1, 3, 5, 10 and 15 years after LT, respectively. Among the 28 DNMs, digestive system tumors were most common, with 17 lesions (60.7%), followed by 3 lesions (11.1%) of lung cancer, 2 lesions (7.4%) of lymphoproliferative diseases, and 1 lesion (3.7%) of cervical cancer, thyroid cancer, soft palate cancer, eyelid cancer, laryngeal cancer, and prostate cancer. The follow-up time of 55.9 (36.6, 102.5) months in the DNMs group after LT was longer than the 33.4 (18.5, 58.9) months in the non-DNMs group ( P<0.001). The 1, 5, and 10 year survival rates of patients with DNMs after LT were 96.3%, 83.5%, and 49.8%, respectively. The 1, 5, and 10 year survival rates of patients with non-DNMs after LT were 94.5%, 77.7%, and 75.4%, respectively. There was no significant difference in the cumulative survival rates between the two groups (log rank=0.402, P=0.526). Conclusion:The incidence of DNMs in LT recipients was 4.3%. The majority of them were digestive system tumors. Early diagnosis and treatment of DNMs significantly improved the prognosis and quality of life of these patients.

Objective:To optimize the matrix formulation of Erhuang analgesic gels. Methods:Central composite design-response surface methodology was adopted to optimize the best formulation of Erhuang analgesic gels by using carbomer 940, triethanolamine and glycerine as independent variables, the appearance, stability, viscosity and in vitro release of berberine hydrochloride as comprehensive evaluation indices. Results:The fitting regressing equation was Y= 82.25 + 4.95 A+ 5.19 B + 1.41 C+ 1.51 AB + 0.904 0 AC- 0.531 9 BC- 2.92 A2-1.80 B2-0.182 1 C2. P value of the model was less than 0.000 1, and the correlation coefficient r value was 0.977. The optimal formulation of Erhuang analgesic gels consisted of 1.84% carbomer 940, 1.30 times triethanolamine of carbomer 940 and 13.99 grams of glycerine. The average comprehensive scores of three verification experiments was 88.56, and the deviations from the predicted values were 2.93%, 2.85% and 1.55%. Conclusion:The formulation process by central composite design-response surface methodology was stable and the formulation of Erhuang analgesic gels has been optimized.

Objective:To retrospectively analyze the long-term survival (10-15 years) and late toxicity of nasopharyngeal carcinoma (NPC) patients after intensity-modulated radiotherapy (IMRT), aiming to provide reference for the optimal treatment of NPC.Methods:132 patients with NPC who were treated with IMRT in Sichuan Cancer Hospital from 2003 to 2009 were recruited. Among them, 3 patients were classified as stage Ⅰ, 22 cases of grade Ⅱ, 61 cases of grade Ⅲ, 43 cases of Ⅳ A and 3 cases of Ⅳ B, respectively. The median dose was 73.37Gy (66 to 85Gy), divided into 33 times. Twenty patients received radiotherapy alone, 112 cases of concurrent radiochemotherapy. The survival rate was calculated by Kaplan-Meier method and log- rank test. Univariate prognostic analysis was performed. Cox model was used to conduct multivariate prognostic analysis. The late radiation toxicity was evaluated by RTOG/EORTC criteria. Results:The median follow-up duration was 128 months (range, 3 to 191 months). The 10-and 15-year local control rates of NPC patients were 86.0% and 79.9%. The disease-free survival rates were 72.5% and 63.2%, and the overall survival (OS) rates were 65.2% and 57.1%. The local recurrence rate was 12.1%, and the distant metastasis rate was 16.7%. A total of 53 patients died, of whom 15 patients died of local recurrence, 20 patients died of distant metastasis and 18 patients died of other diseases (pneumonia, intracranial hemorrhage and accident, etc.). The 10-and 15-year non-tumor-related mortality rates were 11.3% and 13.6%. Univariate analysis showed that age, smoking habit, lactate dehydrogenase (LDH), T stage and clinical stage were the independent prognostic factors of OS in NPC patients. Multivariate analysis demonstrated that LDH, T stage and synchronous chemotherapy were the prognostic factors of OS in NPC patients. The incidence of gradeⅠ-Ⅱ late radiation injury (hearing impairment, dysphagia, dental caries and xerostomia) was 90.4%, and 8.5% for grade Ⅲ-Ⅳ late radiation injury (skin fibrosis, hearing impairment and radiation brain injury).Conclusions:The 10-and 15-year OS of NPC patients treated with IMRT is relatively high. With the prolongation of survival, the non-tumor-related mortality rate is increased. Distant metastasis is the main cause of treatment failure. The main late injuries include grade Ⅰ/Ⅱ hearing impairment, dysphagia, dental caries and xerostomia.

Objective:To optimize the extraction process of Huoxue-Sanyu effervescent tablets. Methods:The hydroxysafflor yellow A content, paeoniflorin and dry extract yield were used as the evaluation indexes, by using analytic hierarchy process (AHP) method, integrative graded indicators method combined with orthogonal test and back propagation (BP) artificial neural network. To optimize the technics parameters, such as the amount of water, extraction time and frequency.Results:Paeoniflorin and hydroxysafflor yellow A showed good linear relation in the range of 0.079 5-1.590 4 μg and 0.038 5-1.539 2 μg respectively, with the average recovery rates of 98.18% and 96.22%. RSD was 0.77% and 1.31% respectively. The optimum extraction technic was 9 times of water, 3 times of heating reflux extraction, and each extraction last for 1 hour. Conclusions:The optimized combined method of orthogonal experiment and BP artificial neural network is practical with high efficiency. The optimal extraction process is stable and reasonable.