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.

Carbamate pesticides, a new type of broad-spectrum pesticides for controlling pests, mites, and weeds, are developed to address the shortcomings of organochlorine and organophosphorus pesticides. Their widespread use and slow degradation have led to environmental pollution, causing damage to ecosystems and human health. Managing pesticide residues is a pressing issue in the current environmental protection. This study aims to investigate the expression of SyEst870, a member of the SGNH/GDSL hydrolase family in Sphingobium yanoikuyae, in a prokaryotic system and evaluate the ability of the recombinant protein to degrade carbamate pesticides. The prokaryotic expression vector pET-32a-SyEst870 was constructed and transformed into the Escherichia coli BL21 for heterologous expression. The purified protein was studied in terms of enzyme activity and effects of temperature, pH, and metal ions on the enzyme activity, with p-nitrophenol acetate as the substrate and based on the standard curve of p-nitrophenol. LC-MS (liquid chromatography-mass spectrometry) was employed to examine the degradation effects of SyEst870 on carbaryl, metolcarb, and isoprocarb. GC-MS (gas chromatography-mass spectrometry) was employed to detect the degradation products of SyEst870 for the three pesticides. The soluble protein SyEst870 was successfully obtained through the heterologous expression in Escherichia coli, which yielded an enzyme with the activity of 677.5 U after affinity chromatography. SyEst870 exhibited degradation rates of 82.34%, 84.43%, and 92.87% for carbaryl, metolcarb, and isoprocarb, respectively, at an initial concentration of 100 mg/L within 24 h at 30 ℃ and pH 7.0. The primary degradation products of carbaryl were identified as α-naphthol and methyl isocyanate. Metolcarb was mainly degraded into m-cresol and methyl isocyanate, and isoprocarb was mainly degraded into 2-isopropylphenol and methyl isocyanate. Compared with the half-life of carbamate pesticides in the natural environment, which ranges from a few days to several weeks, the recombinant protein SyEst870 can rapidly eliminate the residues of carbamate pesticides. This study lays a foundation for addressing pesticide residues in the environment and in fruits and vegetables.
Escherichia coli/metabolism* ; Sphingomonadaceae/genetics* ; Recombinant Proteins/metabolism* ; Biodegradation, Environmental ; Esterases/metabolism* ; Pesticides/isolation & purification* ; Carbamates/isolation & purification*

Objective: To report 3 cases of multiple myeloma (MM) with lung cancer.Combined with literature review to improve the understanding of MM with lung cancer. Methods: The clinical characteristics, treatment and prognosis of 3 cases of MM with lung cancer in Shijingshan Teaching Hospital of Capital Medical University from January 2017 to December 2018 and the relevant literature were retrospectively reviewed. Results: Among the 3 patients, 2 cases were male and 1 case was female, with an average age of 69.7 years.The pathological type of lung cancer patients was adenocarcinoma, of which 2 cases were positive for EGFR gene mutation and 1 case was positive for ALK fusion gene.Three cases of multiple myeloma were all IgG-kappa light chain type, with stage Ⅲ A. The chemotherapy regimens used in MM patients were all PD regimen 4-6 cycles; one patient died of pulmonary infection, one patient had MM CR, but lung cancer progressed, one patient had MM very good partial remission (VGPR), and there was no recurrence of lung cancer. Conclusion The pathogenesis of second primary malignancy in MM is not clear, which needs further study.

OBJECTIVETo compare the effects of neoadjuvant chemotherapy and adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer using propensity score matching method.

METHODSClinical data of patients with locally advanced gastric cancer undergoing open D2 radical gastrectomy between January 2012 and December 2014 at the Affiliated Tumor Hospital of Zhengzhou University were analyzed retrospectively. Sixty-five patients receiving neoadjuvant chemotherapy (NAC) were allocated into the NAC group and 1243 patients receiving postoperative adjuvant chemotherapy (AC) were allocated into the AC group.

INCLUSION CRITERIA(1) age ranged from 18 to 75 years old, and biopsy specimen was confirmed as adenocarcinoma; (2) all the operative procedures were open D2 radical gastrectomy;(3)image examinations showed no distant metastasis or other unresectable factors.

EXCLUSION CRITERIAno open D2 radical gastrectomy, undergoing laparoscopic surgery, neoadjuvant chemotherapy course <2 cycles, without adjuvant chemotherapy, history of other malignancies, severe complications, incomplete data. SOX (tegafur-gimeracil-oteracil plus oxaliplatin) or XELOX (capecitabine plus oxaliplatin) was used as neoadjuvant and postoperative adjuvant chemotherapy regimen. One-to-two propensity score matching was performed to balance the covariance between two groups. Survival was analyzed using the Kaplan-Meier method. Differences between the curves were tested using log-rank test.

RESULTSAfter balancing the covariates including gender, age, tumor location, degree of differentiation, clinical stage, chemotherapy regimen, chemotherapy course and surgical approach, 195 patients were enrolled, including 65 patients of the NAC group and 130 patients of the AC group. The number of harvested lymph nodes in NAC and AC group was 22.3±4.6 and 22.6±5.1 respectively, without statistically significant difference(t=1.125, P=0.263). Pathological response assessment for NAC group showed TRG0 in 6 cases, TRG1 in 8 cases, TRG2 in 17 cases, TRG3 in 34 cases; sensitive (TRG 0 to 2) in 31 cases (47.7%), non-sensitive in 34 cases (52.3%). The 3-year progression-free survival rate of NAC and AC group was 73.6%(95%CI: 62.8-84.3) and 69.9%(95%CI:62.1-77.7) respectively, which was not significantly different(P=0.361). The 3-year overall survival rate of NAC and AC group was 80.0%(95%CI:70.2-89.8) and 74.6%(95%CI:67.2-82.0) respectively, which was not significantly different as well(P=0.387). Subgroup analysis revealed that the 3-year progression-free survival rate and 3-year overall survival rate of sensitive patients in NAC group were 83.3%(95%CI:70.0-96.6) and 87.1%(95%CI:75.3-98.9) respectively, which were significantly higher than 62.4%(95%CI:46.1-78.7, P=0.037) and 70.2%(95%CI:54.7-85.7, P=0.033) of non-sensitive patients in NAC group, and those in AC group(P=0.044 and P=0.040).

CONCLUSIONSEffects of neoadjuvant chemotherapy and postoperative adjuvant chemotherapy on the prognosis of patients with locally advanced gastric cancer are similar. Patients who are sensitive to neoadjuvant chemotherapy have better prognosis. It may be beneficial to improve prognosis that some appropriate patients with locally advanced gastric cancer are screened for neoadjuvant chemotherapy.

Objective To evaluate the clinical significance of detecting platelet parameters in platelet transfusion patients by Investigating the relationship between platelet parameters and efficacy of platelet transfusion and prognosis.Methods A total of 50 patients who underwent platelet transfusion in our hospital in 2014 to 2016 were reviewed.Patients divided into two groups (with normal platelet counts group or subnormal platelet counts group) according to outcomes of blood biochemistry and routine after five days of platelets transfusion.Platelet parameters (platelet count,platelet distribution width,mean platelet volume,large platelet ratio) and CCI were evaluated by statistical analysis.Results The numbers of patients with CCI＞4.5 in normal platelet counts group is 21 (77.78％),that in subnormal platelet counts group is 11 (47.83％).Platelet parameters before transfusion showed no significant difference between two groups (P＞ 0.05).After transfusion,in normal platelet counts group Plt,PDW,MPV and P-LCR were significantly higher than another group (P＜0.01).MPV and P-LCR were increased in normal platelet counts group,and decreased in normal platelet counts group after transfusion.Condusion Detection of platelet parameters,especially MPV and P-LCR,is important for evaluating the efficacy and prognosis of platelet transfusion.

BACKGROUND:In the clinical orthodontics, ceramic brackets have deficiencies in the aspects of antibacterial and mechanical properties, which easily lead to the emergence of a variety of adverse events and influence the orthodontic effect. OBJECTIVE:To observe the antibacterial and mechanical properties of nano silver hydroxyapatite coating ceramic brackets. METHODS:The nano silver hydroxyapatite coating ceramic brackets were prepared. Scanning electron microscopy was used to observe the coating surface. Coating antibacterial experiment was conducted. Totaly 50 in vitro human maxilary premolars were randomly divided into two groups (n=25 per group): experimental and control groups. Premolars in the experimental group were bonded to nano silver coating hydroxyapatite ceramic brackets, and premolars in the control group were bonded to ordinary ceramic brackets. The shear strength was detected in these two groups.RESULTS AND CONCLUSION: The overall structure of nano silver hydroxyapatite coating was order, uniform and compact. Hydroxyapatite had a porous structure with a micro-nanometer aperture and there were a large number of nano-silver particles uniformly distributed. Quantitative antibacterial experiments showed that nano silver hydroxyapatite coating ceramic brackets had a strong inhibition to Escherichia coli and Staphylococcus albus, with an antibacterial rate of more than 95%. The shear strength in the experimental group was lower than that of the control group (P < 0.05). These results demonstrate that the nano silver hydroxyapatite coating ceramic brackets have good antibacterial and mechanical properties, which meet the requirement of mechanical change in the clinical orthodontics.

Inflammation and lung function decline are the main pathophysiological features of chronic obstructive pulmonary disease (COPD). Acupuncture can improve lung function in patients with COPD, but the underlying mechanisms are not well understood. Orexins (OXs), which are found in peripheral plasma, are neuropeptides that regulate respiration and their levels are related to COPD. Therefore, we hypothesized that acupuncture might alter OXs, reduce lung inflammation and improve lung function in COPD.

BACKGROUND: Tissue Doppler echocardiography (TDE) has been proved to evaluate general and local function of heart but less reported on adriamycin-induced cardiomyopathy following bone marrow stromal cell (BMS) transplantation.OBJECTIVE: To evaluate myocardial function of an adriamycin-induced cardiomyopathy rabbit model following BMS transplantation using TDE.DESIGN, TIME AND SETTING: A randomized animal control study was performed at Laboratory of Ultrasound, Union Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology from September 2002 to December 2003.MATERIALS: A total of 28 male adult Japanese rabbits weighing (2.0+0.2) kg were used in this study. Adriamycin was used to induce cardiomyopathy model in 20 rabbits.METHODS: Twenty-eight male Japanese rabbits were randomly divided into three groups: cell transplantation group (n=10),PBS group (n=10), and sham operation group (n=8). BMSs were isolated from cell transplantation group at the 8th day. On the 12th week, cells were labeled with 4, 6-diamidino-2-phenylindole (DAPI), and then epicardial directly injected into the myocardium of the same rabbits in thoracotomy surgery. Non-cell only culture fluid PBS was injected in PBS group. Sham operation group underwent thoracotomy surgery with the same volume of saline injection.MAIN OUTCOME MEASURES: Left ventricular function was assessed by conventional and tissue Doppler echocardiography before and 4 weeks after surgery. Histological examination including apotisis study and DAPI fluorescent were assessed after sacrificed.from (4.0+1.1) cm/s to (5.3+1.2) cm/s (P ＜ 0.05) around the inject site, but the improvement of global myocardial function was not found by conventional echocardiography. In PBS and sham operation group there were no differences in global and myocardium at 4 weeks after transplantation. Histological findings showed that the injury of the myocardium around the injection site was relieved with less apoptosis.

Objective To investigate the effect on bioeffects such as sonoporation and cell killing that induced by domestic ultrasound contrast agent(perfluoropropane-albumin microsphere)and diagnostic ultrasound by microbubble concentration.Methods Suspensions of hepatocyte with microbubbules in different concentrations were exposed to diagnostic ultrasound.The study included blank contrast group(no microbubble,no ultrasound),exposed group(no microbubble,exposed to ultrasound)and 6 microbubble groups in different concentration(with different microbubbule/cell ratios for 1,5,10,50,100 and 200,exposed to ultrasound for 10min).The uptake of fluorescein isothiocyanatedextran(FD500)by hepatocyte was observed and the percentages of sonoporation cells were counted,the cell viability was determined by trypan blue stain immediately after exposure,and apoptosis of ceils were detected by flow cytometry,with double staining of fluorescein isothiocyanate(FITC)-labeled Annexin V/propidium iodide(PI).Results Fluorescence stain results:compared with blank contrast group or exposed group,the sonoporatin of groups with microbubble/cell ratio of 5 to 200 increased significantly(P＜0.05).Cell killing effects:compared with the blank contrast group,only the cell death percentages of microbubble groups with microbubble/cell ratio of 50,100 and 200 increased significantly(P＜0.05).Compared with the exposed group,only that of groups with microbubble/cell ratio of 100 and 200 increased significantly(P＜0.05).There was no significant different between blank contrast group and exposed group for all these results.Conclusions Sonoporation and cell killing effect can be induced by diagnostic ultrasound in HL-7702 with domestic ultrasound contrast agent(perfluoropropane-albumin microsphere).For diagnosis,the ratio of microbubbule/cell should better be under 10.While for gene transfection,the ratio should better be 50 and could be 100 if it is necessary.