Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphory-lation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drug-containing serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while pro-portion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-α were significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusion:XSTMD effectively treats DVT by pre-cisely regulating the JAK2/STAT3 signaling pathway to promote the differentiation of DCs into pDC and alleviate inflammatory injury.

Objective:To investigate the molecular mechanism of Xiaoshuantongmai Decoction(XSTMD)targeting JAK2/STAT3 signaling pathway to regulate the function of dendritic cells(DCs)in treatment of deep vein thrombosis(DVT).Methods:After treatment of DVT with XSTMD,expressions of fibrinogen beta chain(FGB)and D-dimer(D2D)protein in plasma of patients with DVT were detected by ELISA,proportion of plasmacytoid dendritic cell(pDC)and conventional dendritic cell(cDC),and expression of HLA-DR protein in peripheral blood mononuclear cells(PBMCs)of patients with DVT were detected by flow cytometry,expressions of CD80 and CD86 mRNA were detected by qRT-PCR,Western blot was used to detect protein levels of JAK2,STAT3 and phosphory-lation(p-JAK2 and p-STAT3)in PBMC of DVT patients and mice.LPS-induced mouse DC2.4 cells were treated with XSTMD drug-containing serum.Western blot was used to determine the protein levels of JAK2,STAT3,p-JAK2 and p-STAT3.ELISA was used to detect protein levels of IL-6,TNF-α,IL-10 and TGF-β1 in cell culture supernatant.Results:After treatment with XSTMD,weight and length of thrombus were significantly reduced in mice with DVT(P<0.001).Compared with before treatment,expressions of FGB and D2D were significantly decreased in plasma of DVT patients(P<0.001),proportion of pDC was significantly increased,while pro-portion of cDC was significantly decreased in PBMC of DVT patients(P<0.01),expression of HLA-DR protein and mRNA levels of CD80 and CD86 were significantly decreased in PBMC of DVT patients(P<0.05,P<0.01,P<0.001)after treatment with XSTMD.Levels of p-JAK2 and p-STAT3 protein were significantly increased in PBMC from DVT patients and mice treated with XSTMD(P<0.05).After treatment with serum containing XSTMD,protein levels of p-JAK2 and p-STAT3 induced by LPS were significantly increased in murine DC2.4 cells(P<0.05).Protein expressions of IL-6 and TNF-α were significantly decreased,while protein expressions of IL-10 and TGF-β1 were significantly increased in cell supernatant(P<0.01,P<0.001).Conclusion:XSTMD effectively treats DVT by pre-cisely regulating the JAK2/STAT3 signaling pathway to promote the differentiation of DCs into pDC and alleviate inflammatory injury.

Objective To explore the feasibility of radiomics features combined with different machine learning methods based on CT scans to predict lymphovascular and perineural invasion in patient with gastric cancer.Methods A total of 142 patients with gas-tric cancer lymphovascular confirmed by operative pathological examination were retrospectively selected.Among all patients,there were 96 positive cases and 46 negative cases.Among 137 patients with perineural invasion,there were 76 positive cases and 61 nega-tive cases.The 3D-Slicer package was used for delineation,and the Pyradiomics package was used to extract radiomics features.All data were randomly divided into training set and test set in an 8∶2 ratio.Intraclass correlation coefficient(ICC),Pearson correla-tion analysis,least absolute shrinkage and selection operator(LASSO)algorithm were used for feature selection.Support vector machine(SVM),K-nearest neighbor(KNN),decision tree(DT),random forest(RF),extreme tree(ET),extreme gradient boosting(XGBoost),and LightGBM were used to compare the models of lymphovascular and perineural invasion,respectively.Receiver operating characteris-tic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive performance of these models.Results The lymphovascular group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.926,0.753,1.000,0.999,1.000,1.000,and 0.917,and the AUC in the test set were 0.894,0.692,0.456,0.678,0.753,0.650,and 0.650,respectively.The perineural invasion group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.864,0.794,1.000,1.000,1.000,1.000,and 0.866,and the AUC in the test set were 0.861,0.706,0.700,0.672,0.731,0.667,and 0.678,respectively.Conclusion Based on venous phase CT radiomics features combined with machine learning methods,it is feasible to predict lymphovascu-lar and perineural invasion of gastric cancer preoperatively.Among the variousmachine learning methods,SVM shows the best predictive performance for lymphovascular and perineural invasion in patient with gastric cancer.

Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.

Objective:To explore the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of relapsed/refractory acute myeloid leukemia (AML).Methods:The clinical data of 35 patients with relapsed/refractory AML treated with allo-HSCT in the Affiliated Cancer Hospital of Zhengzhou University from June 2011 to October 2018 was retrospectively analyzed. The overall survival (OS), disease-free survival (DFS), graft versus host disease (GVHD) incidence, transplantation related mortality and recurrence rate were calculated, and the risk factors affecting prognosis were analyzed.Results:Hematopoietic reconstitution was obtained in all patients after transplantation. The 100 d incidence of grade Ⅱ-Ⅳ acute GVHD was (22.9±7.7)%, and the 3-year incidence of chronic GVHD was (49.5±10.60)%. The median follow-up time after transplantation was 14.1 months (4.2-89.4 months). In all cases, 18 cases survived (including 16 cases of DFS), and 17 cases died. Fourteen cases relapsed, and the median recurrence time was 4.7 months (2.9-32.4 months). The 3-year OS rate and DFS rate were (44.4±9.3)% and (43.0±9.5)%, respectively. Univariate analysis showed that the non-remission disease before transplantation, poor genetic risk grade before transplantation and recurrence after transplantation were the risk factors for OS (all P < 0.05). The 3-year OS rates in complete remission before transplantation group and non-remission before transplantation group were (63.2±12.0)% and (15.7±12.8)% ( P = 0.025), the 3-year DFS rates were (62.2±12.3)% and (15.3±12.7)% ( P = 0.028), and the 3-year recurrence rates were (28.2±10.7)% and (80.6±15.7)% ( P = 0.057). The 3-year recurrence rate in genetic high-risk group was higher than that in middle-risk group and low-risk group [100.0%, (45.0±12.1)% and (14.3±13.2)%, P = 0.045]. The 3-year tansplantation related mortality was (18.7±7.7)%. Conclusions:Allo-HSCT is an effective method for salvage treatment of relapsed/refractory AML, and recurrence is the main factor affecting survival. Reducing tumor load before transplantation is very important for reducing recurrence and improving curative effect.

Objective To investigate the role of diffusion kurtosis imaging (DKI) in indeterminate solitary pulmonary nodules (SPN) diagnosis and to compare with conventional diffusion weighted imaging (DWI). Methods From March 2016 to Dec 2017, forty-three consecutive patients (30 male, 13 female, age: 56 ± 11 years) with indeterminate SPNs were included. All patients underwent axial multi-b factor DWI (with b values=0, 50, 200, 400, 800, 1400, 2000 s/mm2) examination and were divided into benign group (19 cases) and malignant group (24 cases) according to pathological results of SPN. ADC Kurtosis (K) and Diffusivity (Dk) values were compared between malignant and benign group and among different subtypes of lung cancer using independent t test (normal distribution and homogeneity of variance) and Mann-Whitney U test (skewed distribution or variance). Receiver operating characteristic (ROC) curves were employed to evaluate the diagnostic performance. Results K values were significantly higher for malignant SPNs than for benign SPNs (0.839 ± 0.197 vs. 0.718 ± 0.120;t=2.359, P=0.023). ADC values were found to be significantly higher in benignity than malignant SPNs [(1.605 ± 0.422) × 10-3mm2/s vs. (1.278 ± 0.210) × 10-3mm2/s; t=-3.089, P=0.005). No difference was observed in Dk between the two groups (P=0.922). All parameters cannot differentiate subtypes of lung cancer. The ADC value had higher AUC (area under ROC curve) than that of K value. The sensitivity (70.8％) and accuracy (72.1％) of ADC value was higher than K value, the specificity of both methods was equal. Conclusion DKI is a feasible non-invasive tool which has comparable capability of conventional DWI in SPNs differentiation, although with lower sensitivity and accuracy. DKI can provide additional information for SPNs characterization and has a potential to be a robust way in SPNs interpretation.

OBJECTIVE： To evaluate the accessibility of essential medicine for common chronic disease in primary health care institutions in Hubei province， and to provide evidence for improving essential medicine policy and strengthening the management level of chronic disease. METHODS： The purchase data of essential medicine for 6 kinds of common chronic disease （diabetes， hypertension， gastric ulcer， asthma， rheumatoid arthritis and epilepsy） were collected from centralized drug procurement platform of Hubei province from 2015 to 2017； essential medicin equipping rate was used to evaluate the availability， and minimum daily wage was used to evaluate the affordability. So that accessibility could be analyzed and suggestions for improving accessibility and affordability were put forward. RESULTS： From 2015 to 2017， the equipping rate of essential drugs varied from 40.00％ to 71.43％，and the availability of those medicine for common chronic disease was at a low level. The affordability improved slightly （the ratio of medication cost to minimum daily wage was decreased from 1.91 to 1.79 from 2015 to 2017） but remained low， and the ratio of medication cost to minimum daily wage for more than 70％ of 21 drugs was less than 1. CONCLUSIONS： Since the accessibility of essential medicine for common chronic disease was at a low level in Hubei province， it is suggested to optimize kinds of essential medicine for chronic disease， to promote the construction of hierarchical medical system， to reduce the price of essential medicine for chronic disease， and to improve the compensation mechanism of essential medicine for chronic disease to further strengthen the management of chronic disease in primary health care institutions.

Objective: To evaluate clinical efficacy and safety of microneedle-mediated intradermal injection with hyaluronic acid for the treatment of sensitive skin. Methods: A total of 53 female patients aged 21-54 years and diagnosed with sensitive skin were enrolled from Department of Cosmetic Dermatology, Dermatology Hospital of Southern Medical University from January to June in 2018, and were divided into 3 groups by using a random number generator and a residue-based method: high-pressure jet injection group (n = 23) receiving high-pressure jet injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 2 weeks, microneedle injection group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and microneedle-mediated injection with 0.9% sodium chloride solution on the left side of the face (control side) once every 4 weeks, combination group (n = 15) receiving microneedle-mediated injection with hyaluronic acid on the right side of the face (treatment side) and high-pressure jet injection with hyaluronic acid on the left side of the face (control side) once every 4 weeks. All the patients in the above 3 groups received 4 consecutive sessions of treatment. Before the initial treatment and 2 weeks after the final treatment, erythema and skin pore scores were determined on the right and left sides of the face by using VISIA facial imaging system, lactic acid stinging test was performed, and skin sensitivity including severity of itching, dryness, erythema and scaling was evaluated. Two weeks after the final treatment, the overall improvement was evaluated with the Global Aesthetic Improvement Scale (GAIS) by clinicians and patients. Adverse reactions were recorded during and after treatment. Statistical analysis was carried out by using paired t test, Wilcoxon sign rank sum test and chi-square test. Results: Two weeks after the final treatment, the improvement of skin pore score in the treatment side was superior to that in the control side in the high-pressure jet injection group (t = 2.19, P = 0.03) , while no significant difference in the improvement of erythema score was observed between the treatment side and control side (t = 1.10, P = 0.27) ; in the microneedle injection group, the improvement of erythema and skin pore scores was greater in the treatment side than in the control side (t = 2.47, 3.02, both P = 0.01) ; in the combination group, the VISIA erythema score in the treatment and control sides was 0.59 ± 0.25 and 0.85 ± 0.31 respectively, the improvement of erythema score in the treatment side was superior to that in the control side (t = 5.02, P < 0.01) , while there was no significant difference in the improvement of skin pore score between the treatment side and control side (P > 0.05) . Two weeks after the final treatment, the severity of itching, dryness and scaling was significantly improved in both the treatment and control sides in the 3 groups compared with those before the initial treatment (P < 0.05) , while the severity of erythema was significantly improved only in the treatment side in the microneedle injection group and combination group when compared with that before the initial treatment (Z = -2.236, -2.887, respectively, both P < 0.05) . Moreover, both the microneedle injection group and combination group showed significantly decreased severity of erythema in the treatment side compared with that in the control side two weeks after the final treatment (Z = -2.646, -2.887, respectively, both P < 0.05) . Two weeks after the final treatment, the positive rate of the lactic acid stinging test significantly decreased in the treatment side compared with that before the initial treatment in the microneedle injection group (χ² = 4.821, P = 0.028) , but showed no significant changes in the other groups (all P > 0.05) . No severe adverse reactions were observed during or after the treatment. Conclusion Microneedle intradermal injection with hyaluronic acid can effectively and safely improve erythema, skin pore and sensitive symptoms in patients with sensitive skin.

The efficacy and safety of co-transplantation of unrelated donor peripheral blood stem cells (UD-PBSCs) combined with umbilical cord mesenchymal stem cells (UC-MSCs) in refractory severe aplastic anemia-Ⅱ(RSAA-Ⅱ) were analyzed retrospectively. Fifteen patients with RSAA-Ⅱ underwent UD-PBSCs and UC-MSCs co-transplantation, among whom 14 cases had hematopoietic reconstitution without severe graft versus-host disease (GVHD). The 5-year overall survival rate was 78.57%. Combination of UD-PBSCs and UC-MSCs transplantation could be a safe and effective option for RSAA-Ⅱ.

Background:CBX3 is a member of heterochromatin protein family. Recent studies indicated that CBX3 was closely related to lung cancer,osteosarcoma,gastric cancer. Aims:To investigate the expression and clinical significance of CBX3 in colorectal cancer,and explore the potential mechanism. Methods:Thirty colorectal cancer patients from June 2011 to June 2012 at Shanghai Renji Hospital were enrolled. Real-time quantitative PCR and immunohistochemistry were used to determine mRNA and protein expressions of CBX3 in colorectal cancer tissues and corresponding paracancerous tissues, respectively. Human colorectal cancer cell line RKO was transfected with overexpressed plasmid or siRNA of CBX3. Cell proliferation was measured by CCK-8 assay,Western blotting was implemented to determine the protein expressions of CBX3 and p53. Results:The mRNA and protein expressions of CBX3 were significantly increased in colorectal cancer tissues than in corresponding paracancerous tissues. Increased protein expression of CBX3 was closely correlated with tumor size (P ＝ 0. 025 ),lymph node metastasis (P ＝ 0. 013 )and TNM staging (P ＝ 0. 020 ). After intervention with overexpressed plasmid of CBX3,the mRNA and protein expressions of CBX3 were efficiently upregulated in RKO cells, cell proliferation and protein expression of p53 were significantly increased. Meanwhile,the mRNA and protein expressions of CBX3 were efficiently downregulated in RKO cells after knockdown of CBX3,resulting in significantly decreased cell proliferation and protein expression of p53. Conclusions:CBX3 may promote the proliferation of colorectal cancer cells via influencing the expression of p53,thus promoting the progression of colorectal cancer. This indicates that CBX3 has the potential to be a new target for diagnosis and therapy of colorectal cancer.