OBJECTIVE: To investigate the clinical efficacy, related side-effectt and long-term survival condition of Philadelphia chromosome positive acute lymphoblastic leukemia (Ph ALL) patients treated with second generation TKI dasatinib and chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Clinical data of 19 newly diagnosed as Ph ALL patients treated by dasatinib, chemotherapy and allo-HSCT from January 2012 to September 2018 were collectd and analyzed. RESULTS: There were 10 males and 9 females with median age of 29 years old. 14 patients were BCR/ABL P190 positive while 5 with BCR/ABL P210 positive. Three patients had complex karyotype, and 3 cases were confirmed to have central nervous system leukemia. All the patients received treatment with the induction chemotherapy regimen of VDCLP and consolidation regimens such as HD-MTX and MAE. 11 patients (57.9%) received dasatinib during induction chemotherapy, 3 patients (15.8%) received dasatinib after remission and 5 patients (26.3%) received dasatinib to replace imatinib. Side-effect appeared in 3 patients including rash, edema and nausea. All the patients got morphological remission and 7 patients(63.6%) got MMR after 4 weeks of induction chemotheraphy. 17 patients (89.5%) got MMR and 15 patients(78.9%) got CMR before allo-HSCT. All the patients received related bone marrow and peripheral hematopoietic stem cell transplantation from related donors, the median time of WBC and platelet engraftment were 12 d and 14 d after transplantation, respectively. The incidence rate of aGVHD and cGVHD were 42.1% and 57.9% respectivety. 13 patients received therapy of dasatinib after HSCT but 7 patients discontinued because of severe headache, vomiting and serious effusions. All the patients were followed-up for the median time of 42 months, the 3-year and 5-year OS both were 94.4%, and 3-year and 5-year RFS of 81.9% and 71.6%, respectively. CONCLUSION First-line administration of dasatinib and chemotherapy followed by allo-HSCT for treatment of PhALL is effective and patients can well-tolerate, the patients long-tern survival maybe superior to that of the patients treated with first generation TKI.

OBJECTIVE: To investigate the clinical manifestations pathologic features, treatment options and prognosis of patients with bone lymphoma. METHODS: The clinical characteristics, pathologic features, treatment and prognosis of 34 BL patients diagnosed by histopathologic method or/and PET-CT and treated in first hospital of peking university from January 2004 to April 2018 were analyzed retrospectively. RESULTS: The median age of 34 BL patients was 56 years old, the male and female ratio was 1.43∶1 (24 /10). Among 34 patients, the patients with primary bone lymphoma(PBL) were 8 cases, the patients with secondary bone lymphoma(SBL) was 26 cases, the PBL and SBL ratio was 0.31∶1. Bone lymphoma lacks typical systemic symptoms, and its onset began mostly from bone pain and pathologic bone fracture. The most frequent pathological type of bone lymphoma in our study was diffuse large B-cell lymphoma (DLBCL), accounting for 55.88%. At present, the conventional treatment for bone lymphoma includes chemotherapy, or chemotherapy combined with radiotherapy and surgery, as well as hematopoietic stem cell transplantation. The average and median OS time of BL patients were 349 years and 3 years respectively, meanwhile the OS rate for three years and two years were 56.25% and 78.16%, respectively. Factors that affect survival of BL patients were PBL and SBL classification, pathological type, blood LDH level, and treatment methods. CONCLUSION Bone lymphoma is usually concealed onset，an adequate and adequate combination therapy can improve the survival rate and transplantation therapy plays an important role. Primary bone lymphoma is rare, the prognosis of patients with primary bone lymphoma is good, whereas the prognosis of patients with secondary bone lymphoma is poor.
Bone Neoplasms ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma, Large B-Cell, Diffuse ; Male ; Middle Aged ; Positron Emission Tomography Computed Tomography ; Prognosis ; Retrospective Studies

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Bianyanning on acute pharyngitis in rats, and to provide evidence and experimental data for its clinical application. METHODS: The acute pharyngitis of rats was induced by spraying ammonia directly to their throat. The model rats were randomly divided into model control group, the high-, medium- and low-dose group of Bianyanning, while normal rats were used as control group, 10 in each group. After the corresponding drug treatment, the symptoms and manifestations of each group were observed and recorded; 24 hours after last gavaging, blood samples of each group were collected from the abdominal aorta. The serum contents of interleukin 1-beta (IL-1β) and tumor necrosis factor alpha (TNF-α) were detected by ELISA. HE method was used to observe the characteristic of the lung tissues and the transmission electron microscopy method was used to observe the trachea cilia. RESULTS: After the treatment, compared with the model control group, the high-, medium- and low-dose group of Bianyanning, the symptoms of acute pharyngitis such as inflamed and congestive throat were relieved obviously. The morphological changes of lung and bronchus tissues were apparently improved. The contents of IL-1β and TNF-α in serum were decreased significantly. CONCLUSION Compound Bianyanning can promote the recovering process of acute pharyngitis, improve the morphology of lungs and bronchus, which may be related to inhibiting the releasing of the IL-1β and TNF-α in serum.
Animals ; Drugs, Chinese Herbal ; pharmacology ; Interleukin-1beta ; metabolism ; Pharyngitis ; drug therapy ; immunology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC 39.6 ± 1.9 μmol·L) and HepG2 cells(IC 41.5 ± 1.1 μmol·L), respectively. Compound 9 (23S, 24S)-24-[(O-β-D-fucopyranosyl)oxy]-3β, 23-dihydroxy-spirosta-5, 25(27)-diene-1β-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[β-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC 33.6 ± 2.1 μmol·L).

Five new polyhydroxylated furostanol saponins were isolated from the roots and rhizomes of Tupistra chinensis, and their structures were determined as tupistrosides J-N (1-5), together with four known furostanol saponins (6-9), on the basis of physico-chemical properties and spectral analysis. Among them, compounds 3 and 5 showed cytotoxicity against human cancer cell lines SW620 with IC values of 72.5 ± 2.4 and 77.3 ± 2.5 μmol·L, respectively. Compound 4 showed cytotoxicity against human cancer cell line HepG2 with IC value of 88.6 ± 2.1 μmol·L.

Circular RNAs (circRNAs) are a class of endogenous, covalently closed, single-stranded RNA without 3'-poly(A) and 5'-cap structures. CircRNAs are characterized by universality, diversity, stability and conservation, and have been found to regulate mammalian transcription and be translated into proteins. In this review, we summarized the biogenesis, classification, expression, distribution, biological functions and regulation of circRNAs. In addition, we discussed the association of circRNAs with diseases and the methods for identification and characterization of circRNAs. Finally, we speculated the application prospect and research direction of circRNAs.
Animals ; RNA ; genetics ; Research ; trends

Objective: To analyze the features and patterns of acupoint selection in acupuncture-moxibustion treatment of chronic atrophic gastritis (CAG) by data mining technique. Methods:Relevant clinical studies published before 25 June, 2017 were searched in databases including PubMed, EMBASE, Cochrane library, Chinese Biomedical Literature Database (CBM), China National Knowledge infrastructure (CNKI), and Wanfang Academic Journal Full-text Database (Wanfang). Results:A total of 122 papers were included, involving 69 points. It was found that the top three points on the frequency list were Zusanli (ST 36), Zhongwan (CV 12) and Weishu (BL 21). The points selected were distributed in 11 meridians, in which the Stomach Meridian of Foot Yangming, Conception Vessel, and Bladder Meridian of Foot Taiyang ranked the top and accounted for 74.0％ of the total frequency. Of the involved specific points, Five Shu-Transmitting points, crossing points and Back-Shu points ranked the top, accounting for 47.1％. The analysis of association pattern has shown that Zusanli (ST 36) and Zhongwan (CV 12) won the highest support rate in the paired groups; Zusanli (ST 36), Weishu (BL 21) and Zhongwan (CV 12) had the highest support rate among the point groups. The Five Shu-Transmitting points and the Lower He-Sea points had the highest support rate among the specific point groups. Conclusion: The data mining results of the studies on acupuncture-moxibustion for CAG are substantially in line with the acupuncture-moxibustion treatment theories in traditional Chinese medicine. The results can reflect the acupoint selection patterns in treatment of CAG and provide reference for acupuncture-moxibustion treatment of CAG in clinic.

Objective: To investigate the in vitro and in vivo effects of apatinib in esophageal squamous cell carcinoma and the underlying mechanisms. Methods: The esophageal cancer cells, KYSE-150 and ECA-109, were divided into control group and apatinib treatment group at the concentrations of 2.5, 5, 10, 20 and 40 μmol/L respectively. All of experiments were performed in triplicate. MTT and colony formation assays were used to measure cell proliferation. Transwell assay was used to determine the migration capacity. The effect of apatinib on cell cycle and apoptosis was analyzed by flow cytometry. The expression of VEGF and VEGFR-2 was measured by real-time quantitative PCR (qRT-PCR). The concentration of VEGF in the cell supernatant was assessed by enzyme-linked immunosorbent assay (ELISA). The expression levels of MEK, ERK, p-MEK, p-ERK, JAK2, STAT3 and p-STAT3 after VEGF stimulation were detected by Western blot. Furthermore, the nude mice xenograft model was established. The tumor-bearing mice were randomly divided into control group, apatinib low dose treatment group (250 mg) and apatinib high dose treatment group (500 mg), respectively. Tumor inhibition rates of different groups were calculated. And then the expressions of VEGF and VEGFR2 were detected in xenograft tissues by immunohistochemical staining. Results: In the presence of 20 μmol/L and 40 μmol/L of apatinib for 24 hours, the migration cell numbers of KYSE-150 and ECA-109 were 428.67±4.16 and 286.67±1.53 as well as 1 123.67±70.00 and 477.33±26.84, respectively, that were significantly lower than control group (P<0.05 for all). In addition, after treatment with 10 μmol/L, 20 μmol/L and 40 μmol/L of apatinib for 7 days on KYSE-150 and ECA-109, the colony formation rates were (65.12±25.48)%, (58.19±24.73)% and (29.10±22.40)% as well as (70.61±15.14)%, (61.12±17.21)% and (43.09±11.13)%, respectively. The colony formation rates of 20 μmol/L and 40 μmol/L of apatinib treatment groups were significantly lower than control group (100.00±0.00, P<0.05). The cell cycle ratio of G₂/M phase and apoptosis rate of control group and 20 μmol/L apatinib group in KYSE-150 cells were (12.14±2.13)% and (3.49±0.74)% as well as (26.27±3.30)% and (15.65±1.54)%, respectively. The corresponding ratios in ECA-109 cells were (3.44±0.57)% and (6.31±1.43)% as well as (22.64±2.36)% and (49.26±1.62)%, respectively. The results show that apatinib suppressed cell cycle progression at G₂/M phase and induced cell apoptosis in both KYSE-150 and ECA-109 cells (P<0.05 for all). In the presence of 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the relative levels of VEGF mRNA were (42.57±10.43)% and (25.69±1.24)%, and those of VEGF-2 mRNA were (36.09±10.82)% and (13.99±6.54)%, which were all significantly decreased compared to control group (100.00±0.00, P<0.05 for all). For ECA-109 cells, the relative expression of VEGF and VEGFR2 showed similar tendency (P<0.05 for all). Moreover, after treatment with 20 μmol/L and 40 μmol/L of apatinib in KYSE-150 cells, the VEGF concentrations were (766.48±114.27) pg/ml and (497.40±102.18)pg/ml, which were significantly decreased compared to control group [(967.41±57.75) pg/ml, P<0.05)]. The results in ECA-109 were consistent (P<0.05). Furthermore, after treatment with 40 μmol/L of apatinib in KYSE-150 and ECA-109, the relative expression of p-MEK and p-ERK were 0.49±0.05 and 0.28±0.03 as well as 0.63±0.03 and 1.22±0.15, which were significantly lower than control group (1.23±0.19 and 0.66±0.07 as well as 1.03±0.20 and 1.76±0.20; P<0.05). The relative expression of STAT3, p-STAT3 in control group and experimental group were 0.96±0.15 and 0.85±0.16 as well as 0.62±0.09 and 0.36±0.13, respectively. The results showed that the protein levels of STAT3 and p-STAT3 were significantly lower than the control group (P<0.05 for all). The inhibition rates of apatinib in xenograft nude mice were 29.25% and 19.96% for 250 mg and 500 mg treatment groups. The concentration of VEGF were (25.11±4.12) pg/ml, (16.40±2.81) pg/ml and (15.04±4.88)pg/ml for control, 250 mg and 500 mg treatment groups, respectively. Conclusions Apatinib can inhibit cell proliferation, induce apoptosis and suppress migration of esophageal cancer cells in vitro and in vivo. This effect was mainly mediated via the alterations of Ras/Raf/MEK/ERK pathway and JAK2/STAT3 pathway.

BACKGROUND: Wharton's Jelly-derived mesenchymal stem cells are relatively primitive stem cells that are ideal vectors for gene therapy. However, there is a lack of studies on the conditions for the electrotransfection of Wharton's Jelly-derived mesenchymal stem cells. Therefore, exploring the optimal conditions for the electrotransfection of Wharton's Jelly-derived mesenchymal stem cells occupies an important position. OBJECTIVE: To investigate the effects of different electroporation conditions on the transfection efficiency of Wharton's Jelly-derived mesenchymal stem cells, and to explore the optimal conditions for cell electroporation. METHODS: By controlling the transfection conditions such as voltage, pulse duration and cell status, EEV-EGFP plasmids were transfected into Wharton's Jelly-derived mesenchymal stem cells by electroporation under different conditions. Transfection efficiency was detected by flow cytometry. RESULTS AND CONCLUSION: (1) The transfection efficiency was intended to increase when the voltage ranged from 125 V to 150 V, and the maximum transfection efficiency was obtained when the voltage was 150 V. However, when the voltage was further increased to 170 V, the transfection efficiency began to decrease considerably. (2) The maximum transfection efficiency was obtained when the pulse duration was 5.0 ms, while it was certainly decreased when the pulse duration was 2.5 and 7.5 ms. (3) The transfection efficiency of the cells cultured under normoxia was higher than that under hypoxic culture. These findings reveal that normally cultured Wharton's Jelly-derived mesenchymal stem cells can achieve higher electroporation efficiency via two pulse sessions at a voltage of 150 V, pulse duration of 5.0 ms, and pulse interval time of 50 ms.

Objective To compare the clinical effect of nasal intubation with domestic video intubationscope and Macintosh direct laryngoscope. Methods One hundred patients scheduled for oro-maxillo-facial operation, American Society of Anesthesiologists (ASA) grade I or II, aged 19 ~ 67 years, were randomly divided into the domestic video intubationscope group (group V) and the Macintosh direct laryngoscope group (group M), with 50 cases in each group. Nasal intubation was respectively performed with domestic video intubationscope (Group V) and Macintosh direct laryngoscope (group M). Cormark-Lehane grade (C-L classification), tracheal intubation time, first-time intubation success rate and tracheal intubation complications were recorded.Mean arterial pressure (MAP) and heart rate (HR) of before induction of anesthesia (T0), after induction of anesthesia (T1), at glottic exposure (T2), at intubation (T3), 1 min after intubation (T4) and 3 min after intubation (T5) were recorded. Results C-L classification in group V was significantly lower than that in group M (P < 0.05), intubation time in group V was significantly shorter than that in group M (P < 0.05), first-time intubation success rate in group V was significantly higher than that in group M (P < 0.05). Compared with T1, MAP was significantly higher at T3~ T4and HR was significantly faster at T3in group V, MAP was significantly higher at T2~ T4and HR was significantly faster at T2~ T3in group M (P < 0.05). Compared with group M, MAP and HR in group V were significantly lower at T2~ T4 (P < 0.05). The incidence of tracheal intubation complications in group V was significantly lower than that in group M (P < 0.05). Conclusions Compared with Macintosh direct laryngoscope,domestic video intubationscope in nasal intubation is better in glottic exposure,it could shorten tracheal intubation time ,increase first-time intubation success rate, maintain stable hemodynamics, has fewer tracheal intubation complications and is worthy of clinical application.