Objective To investigate the clinical characteristics and prognosis of acute myeloid leukemia(AML)patients with PTPN11 gene mutation.Methods Total 115 adult AML patients who underwent initial diagnosis,treatment,and second-generation sequencing(NGS)detecting at hospital were recruited in this study.Clinical da-ta included disease characteristics,treatment efficacy,long-term prognosis,immune cell subpopulations,and leu-kemia stem cells were collected to analyze the clinical characteristics and prognosis of AML patients with PTPN11 gene mutation.Results PTPN11 gene mutation rate in newly diagnosed adult AML was 9.57％,and the mutation site mainly occurred in exon 3 region with all mutation type being point mutation.Compared with PTPN11 wild-type group,PTPN11 gene mutation group had a higher early mortality rate(18.18％vs 4.00％,P=0.048),a lower complete response rate(33.33％vs 67.71％,P=0.039),a higher recurrence rate(83.33％vs 42.31％,P=0.043),a shorter median overall survival time(9 months vs 20 months,P=0.026),a lower proportion of ef-fector T cells[(1.39±0.12)％vs(3.56±0.46)％,P=0.038],and a higher proportion of leukemia stem cells[(13.82±3.66)％vs(3.87±1.40)％,P=0.021].Conclusion PTPN11 gene mutation is a poor prognostic marker for AML.Those patients have a high early mortality rate,low complete remission rate,high recurrence rate,short median overall survival time,a low proportion of effector T cells,and a high proportion of leukemia stem cells.

The present study optimized the ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair by network pharmacology and Box-Behnken method. Network pharmacology and molecular docking were used to screen out and verify the potential active components of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus, and the process evaluation indexes were determined in light of the components of the content determination under Ziziphi Spinosae Semen and Schisandrae Sphenantherae Fructus in the Chinese Pharmacopoeia(2020 edition). The analytic hierarchy process(AHP) was used to determine the weight coefficient of each component, and the comprehensive score was calculated as the process evaluation index. The ethanol extraction process of Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus was optimized by the Box-Behnken method. The core components of the Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus drug pair were screened out as spinosin, jujuboside A, jujuboside B, schisandrin, schisandrol, schisandrin A, and schisandrin B. The optimal extraction conditions obtained by using the Box-Behnken method were listed below: extraction time of 90 min, ethanol volume fraction of 85%, and two times of extraction. Through network pharmacology and molecular docking, the process evaluation indexes were determined, and the optimized process was stable, which could provide an experimental basis for the production of preparations containing Ziziphi Spinosae Semen-Schisandrae Sphenantherae Fructus.
Ethanol ; Molecular Docking Simulation ; Network Pharmacology ; Seeds/chemistry* ; Ziziphus/chemistry* ; Plant Extracts/chemistry* ; Schisandra/chemistry* ; Fruit/chemistry* ; Technology, Pharmaceutical

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.
Antioxidants ; Aralia ; Chromatography, High Pressure Liquid ; Drugs, Chinese Herbal ; Saponins

OBJECTIVETo compare the long-term outcomes of patients receiving percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), or medical therapy for treatment of chronic total coronary occlusion (CTO).

METHODSThe patients with CTO were selected from a consecutive cohort of patients who underwent coronary angiography (CAG) between 2008 and 2009. The patients with multiple CAG were excluded. The patients received treatments with PCI, CABG, or conservative medication therapy and were followed for major adverse cardiovascular events (MACE) within 5 years.

RESULTSA total of 253 patients were enrolled in this study, including 192 receiving PCI, 48 receiving CABG, and 13 treated conservatively with medications. The baseline clinical characteristics were similar among the 3 groups except for increased low-density lipoprotein (LDL) and total cholesterol (TC) in the medication group, and increased Syndax score in CABG group. During the follow-up, the incidences of MACE, AMI, death, stroke or heart failure did not differ significantly among the 3 groups (P>0.05). However, CABG group showed a higher incidence of the stroke than the other two groups although this difference did not reach a statistically significantly level (P=0.06).

CONCLUSIONOur study did not demonstrate that recanalization offers greater long-term benefits than medications for treatment of CTO, and the patients receiving CABG appeared to have a higher incidence of stroke.

Chronic Disease ; Cohort Studies ; Coronary Angiography ; Coronary Artery Bypass ; Coronary Occlusion ; surgery ; therapy ; Humans ; Incidence ; Percutaneous Coronary Intervention ; Stroke ; epidemiology ; Treatment Outcome

OBJECTIVETo compare the enhanced recovery program after surgery (ERAS) with conventional perioperative management in patients undergoing radical resection for colorectal cancer.

METHODSThe ERAS protocol included a combination of evidence-based and consensus methodology. A total of 597 consecutive patients undergoing elective colorectal resection were randomized to either the ERAS(n=299) or the control group(n=298). Outcomes related to nutrition and metabolism index, stress index, and recovery index were measured and recorded.

RESULTSDemographics and operative parameters were similar between the two groups(P>0.05). The nutritional status of patients in the ERAS group was improved after surgery compared with that of the control group. On postoperative day (POD) 1, the HOMA-IR in the ERAS group was significantly lower than that in the control group(P<0.01). The cortisol level in the control group was elevated on both POD 1(P<0.01) and POD 5(P<0.01) compared to the preoperative level. However, the cortisol level was not increased until POD 5(P<0.01) in the ERAS group. The levels of TNF-α, IL-1β, IL-6, and IFN-γ were reduced in the ERAS group, indicating less postoperative stress responses compared with the control group. In addition, ERAS group was associated with accelerated recovery of gastrointestinal function. The postoperative length of stay [(5.7±1.6) d vs. (6.6±2.4) d, P<0.01] and expense[(15 998±2655) RMB vs. (17 763±3059) RMB, P<0.01] were reduced in the ERAS group. Twenty-eight patients(9.4%) in the control group and 29(9.7%) in the ERAS group developed complications, while the difference was not statistically significant(P>0.05).

CONCLUSIONERAS protocol alleviates surgical stress response and accelerates postoperative recovery without compromising patient safety.

Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms ; surgery ; Female ; Humans ; Male ; Middle Aged ; Perioperative Care ; methods ; Prospective Studies ; Young Adult

OBJECTIVETo study the correlation between the Chinese medicine (CM) syndrome types of the Uighur and Han people and levels of blood lipids and fibrinogen in premature coronary heart disease (PCHD) patients.

METHODSRecruited were 196 Uighur and 189 Han patients with PCHD first confirmed by coronary angiography at the Heart Center of First Affiliated Hospital of Xinjiang Medical University and Traditional Chinese Medicine Hospital Affiliated to Xinjiang Medical University. Another 60 healthy volunteers were recruited as the healthy control group. CM syndromes were typed by physicians or those having higher professional titles at the cardiac internal medicine. The contents of triglyceride (TG) and total cholesterol (TC) were detected using oxidase method. The high-density lipoprotein cholesterol (HDL-C) level was detected using chemical modification enzymic method. The low-density lipoprotein cholesterol (LDL-C) level was detected using selective dissolution. The fibrinogen (FIB) level was detected using Clauss congeal principle.

RESULTSThe CM syndrome types of Uighurs were sequenced as filthy turbidity and phlegm obstruction syndrome (82 cases, 21.3%) > qi deficiency and blood stasis syndrome (61 cases, 15.84%) >cold accumulation in Xin meridian syndrome (39 cases, 10.13%) >Xin-Shen yin deficiency syndrome (14 cases, 3. 63%). The CM syndrome types of the Han nationality were sequenced as qi deficiency and blood stasis syndrome (69 cases, 17.92%) >filthy turbidity and phlegm obstruction syndrome (67 cases, 17.40%) > cold accumulation in Xin meridian syndrome (42 cases, 10.91%) > Xin-Shen yin deficiency syndrome (11 cases, 2.86%). There was no statistical difference in the syndrome type distribution between the two groups (P >0.05). Compared with the healthy control group, the levels of TG, LDL-C, and FIB increased, and the HDL-C level decreased in patients of filthy turbidity and phlegm obstruction syndrome and qi deficiency and blood stasis syndrome of the patient group. The HDL-C level decreased in the Uighur patients of Xin-Shen yin deficiency syndrome, showing statistical difference (P < 0.01, P < 0.05). Compared with the Han people of the same syndrome type, the TG level increased and the HDL-C level decreased in the Uighur patients of filthy turbidity and phlegm obstruction syndrome. The FIB level increased in the Uighur patients of qi deficiency and blood stasis syndrome with statistical difference (P<0.05). In the Uighur patients, filthy turbidity and phlegm obstruction syndrome was positively correlated with TG (r=0.469) and FIB (r=0.464), and negatively correlated with HDL-C (r=-0.382). Qi deficiency and blood stasis syndrome was positively correlated with FIB (r=0.72) with statistical difference (P<0.01, P<0.05). In the Han patients, filthy turbidity and phlegm obstruction syndrome was positively correlated with TG (r=0.445) and FIB (r=0.372), and negatively correlated with HDL-C (r=-0.37). Qi deficiency and blood stasis syndrome was positively correlated with TG (r=0.471) and FIB (r=0.459) with statistical difference (P<0.01, P<0.05).

CONCLUSIONCM syndrome types were correlated with TG, HDL-C, and FIB in PCHD Han and Uighur patients.

Aged ; Asian Continental Ancestry Group ; Case-Control Studies ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Coronary Disease ; blood ; diagnosis ; ethnology ; Female ; Fibrinogen ; metabolism ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Triglycerides ; blood

OBJECTIVEThis paper aims to investigate the anti-tumor mechanism of inactivated Sendai virus (Hemagglutinating virus of Japan envelope, HVJ-E) for murine melanoma (B16F10).

METHODSThe murine dendritic cells (DCs) were treated with HVJ-E, and then the cytokines secreted from DCs and costimulation-related molecules on DCs were measured. Meanwhile, the expression of β-catenin in HVJ-E treated murine melanoma cells was detected. In addition, HVJ-E was intratumorally injected into the melanoma on C57BL/6 mice, and the immune cells, CTL response and tumor volume were analyzed.

RESULTSHVJ-E injected into B16F10 melanoma obviously inhibited the growth of the tumor and prolonged the survival time of the tumor-bearing mice. Profiles of cytokines secreted by dendritic cells (DCs) after HVJ-E stimulation showed that the number of cytokines released was significantly higher than that elicited by PBS (1P<0.05). The co-stimulation-related molecules on DCs were comparable to those stimulated by LPS. Immunohistochemical examinations demonstrated the repression of β-catenin in B16F10 melanoma cells after HVJ-E treatment. Meanwhile, real-time reverse transcription PCR revealed that HVJ-E induced a remarkable infiltration of CD11c positive cells, chemokine ligand 10 (CXCL10) molecules, interleukin-2 (IL-2) molecule, CD4(+) and CD8(+) T cells into HVJ-E injected tumors. Furthermore, the mRNA expression level of β-catenin in the HVJ-E injected tumors was also down-regulated. In addition, B16F10-specific CTLs were induced significantly after HVJ-E was injected into the tumor-bearing mice.

CONCLUSIONThis is the first report to show the effective inhibition of melanoma tumors by HVJ-E alone and the mechanism through which it induces antitumor immune responses and regulates important signal pathways for melanoma invasion. Therefore, HVJ-E shows its prospect as a novel therapeutic for melanoma therapy.

Animals ; Cell Line, Tumor ; Cytokines ; genetics ; metabolism ; Dendritic Cells ; immunology ; physiology ; virology ; Down-Regulation ; Gene Expression Regulation, Neoplastic ; Melanoma ; immunology ; pathology ; virology ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Sendai virus ; physiology ; Virus Inactivation ; Virus Replication ; beta Catenin ; genetics ; metabolism

Background Corneal neovascularization (CNV) is an important cause of visual impairment and graft rejection after allograft corneal transplantation in inflammatory corneal diseases. The mechanisms and therapy relating to CNV are intensely investigated at all times. Objective This study was to evaluate the effect of eicosapentaenoic acid (EPA) on CNV induced by alkali cauterization and its mechanism. Methods The animal models of corneal neovasculation were induced in the right eyes in 72 Sprayue-Dawley rats by putting a piece of 3 mmfilter paper with 1 mol/L NaOH at the center of the cornea for 30 seconds. The rats were then divided randomly into the 0.02 mg EPA treatment group (24 rats) ,0.03 mg EPA treatment group (24 rats) ,model group (24 rats) and normal group (6 rats). EPA of 0.04 ml with doses of 0.02 mg or 0. 03 mg or saline solution of 0. 04 ml was injected subconjunctivally in model rats and immediately after cauterization. The presence of CNV and corneal edema were observed daily by slit lamp biomicroscope. 1,4,7 and 14 days after operation, corneal histopathological examination was performed by hematoxylin and eosin staining. The vascular endothelial cells were stained with CD34 by immunohistochemistry,and the expression of IL-1α,IL-6 mRNA and the nuclear factor-κBp65 ( NF-κBp65 ) proteins was measured by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The use of animals complied with the Regulations for the Administration of Affair Concerning Experimental Animals by Hebei Province( version 1998 ). Results Under the slit lamp, CNV grew slowly from days 2-4 with obvious corneal edema and defect of epithelium. Larger CNV area and less edema were seen from days 7-10. Maximal vessel growth was observed 14 days after injury with thinner vessels in the model group. Histological examination showed that part of the corneal epithelium was damaged;serious corneal edema, more inflammatory cells and a lot of CNV in the stroma were presented in the model group. However, repairing of the corneal epithelium without CNV ,light corneal edema and less inflammatory cells were found in both the 0. 02 mg EPA and 0. 03 mg EPA treatment groups 7 days after alkali cauterization. The relative area of CNV in the 0. 02 mg EPA treatment group was ( 15.80±6.43 )% and ( 11.06±2. 14)% ,and that in the 0. 03 mg EPA treatment group was (16. 10±7.41 )% and (11.06±2. 51 )%, showing significant reduction in comparison with the model group [ (84. 74±7.77)% and (89.63±7.50) % ] 7 days and 14 days after operation ( P＜0. 05 ). Stronger expression of CD34 in the vascular endothelial cells of the cornea stroma was observed in the model group and an absence of CD34 was observed in the EPA-treated groups on the 7th day. RT-PCR revealed that the expression of IL-1α mRNA and IL-6 mRNA was lower in the EPA treatment groups than the model group ( P＜0. 05 ), and Western blot analysis showed that the expression of NF-κB/p65 in the corneas in the EPA treatment groups was significantly lower than that in the model group on the 4th day after operation (P＜0.05).Conclusion Topical application of EPA suppresses CNV induced by alkali burn possibly by inhibiting the expression of NF-κB,IL-1α and IL-6.

Objective To investigate the safe time of sterile equipments used in laminar flow operating room.Methods In ten operations ( Class Ⅰ ) which last 8 or more hours,we sampled preoperative air,surgery equipments 4 h,6 h,8 h pre and intra-operatively,and surgical personnel' s hands for bacterial culture.Results There was no growth of bacteria in the sampling of preoperative air,surgical personnel's hands and surgical instruments during operation,pass rate was 100％.Conclusions The sterile equipments used in the same operation could be used safely for 8 hours in operating room where the condition of Level 100 laminar flow reached.

BACKGROUNDTransarterial chemoembolization (TACE) is the most widely used primary treatment for unresectable hepatocellular carcinoma (HCC) due to its survival benefit, though its clinical effect is still far from satisfactory. Jiedufang (JDF) granule preparation is a commonly used Chinese herbal medicine formula for HCC. The aim of this study was to evaluate the effect of combined therapy with TACE and JDF granule preparation in treatment of unresectable HCC on survival.

METHODSA retrospective study of TACE was performed in 165 patients with unresectable HCC who were admitted between January 2002 and December 2007 in Changhai Hospital, Shanghai, China. Of the 165 patients, 80 patients (study group) received combined therapy consisting of TACE and a long-term maintenance treatment with oral JDF granule preparation, and the remaining 85 patients (control group) received TACE alone. The survival rates of both groups were calculated by the Kaplan-Meier method. Factors possibly affecting survival were assessed by multivariate analysis in the Cox proportional hazard model, such as maximum tumor size, number of lesions, portal vein invasion, and etc.

RESULTSThe median overall survival was 9.2 months (95% CI: 6.94 - 11.46) in the study group versus 5.87 months (95% CI: 4.21 - 7.52) in the control group. In the study group,survival rates of the 1-, 2- and 3-year follow-up were 41.2%, 18.4%, and 9.6%, respectively. Significant independent prognostic factors identified by the Cox regression analysis were as follows: serum hepatitis B surface antigen (HBsAg) (P = 0.014), maximum tumor size (P = 0.027), number of lesions (P < 0.001), portal vein invasion (P < 0.001), and the therapy model (P = 0.006).

CONCLUSIONCombination therapy of TACE and JDF granule preparation may significantly prolong survival of patients with unresectable HCC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; therapy ; Chemoembolization, Therapeutic ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; therapy ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Treatment Outcome