Analysis of the effect of gene mutations on the efficacy of ruxolitinib in patients with myelofibrosis based on second-generation sequencing technology / 中华血液学杂志

Objective: To assess the effect of gene mutations on the efficacy of ruxolitinib for treating myelofibrosis (MF) . Methods: We retrospectively analyzed the clinical data of 56 patients with MF treated with ruxolitinib from July 2017 to December 2020 and applied second-generation sequencing (NGS) technology to detect 127 hematologic tumor-related gene mutations. Additionally, we analyzed the relationship between mutated genes and the efficacy of ruxolitinib. Results: ①Among the 56 patients, there were 36 cases of primary bone marrow fibrosis (PMF) , 9 cases of bone marrow fibrosis (ppv-mf) after polycythemia vera, and 11 cases of bone marrow fibrosis (PET-MF) after primary thrombocytosis (ET) . ②Fifty-six patients with MF taking ruxolitinib underwent NGS, among whom, 50 (89.29%) carried driver mutations, 22 (39.29%) carried ≥3 mutations, and 29 (51.79%) carried high-risk mutations (HMR) . ③ For patients with MF carrying ≥ 3 mutations, ruxolitinib still had a better effect of improving somatic symptoms and shrinking the spleen (P=0.001, P<0.001) , but TTF and PFS were significantly shorter in patients carrying ≥ 3 mutations (P=0.007, P=0.042) . ④For patients carrying ≥ 2 HMR mutations, ruxolitinib was less effective in shrinking the spleen than in those who did not carry HMR (t= 10.471, P=0.034) , and the TTF and PFS were significantly shorter in patients carrying ≥2 HMR mutations (P<0.001, P=0.001) . ⑤Ruxolitinib had poorer effects on spleen reduction, symptom improvement, and stabilization of myelofibrosis in patients carrying additional mutations in ASXL1, EZH2, and SRSF2. Moreover, patients carrying ASXL1 and EZH2 mutations had significantly shorter TTF [ASXL1: 360 (55-1270) d vs 440 (55-1268) d, z=-3.115, P=0.002; EZH2: 327 (55-975) d vs 404 (50-1270) d, z=-3.219, P=0.001], and significantly shorter PFS compared to non-carriers [ASXL1: 457 (50-1331) d vs 574 (55-1437) d, z=-3.219, P=0.001) ; 428 (55-1331) d vs 505 (55-1437) d, z=-2.576, P=0.008]. Conclusion: The type and number of mutations carried by patients with myelofibrosis and HMR impact the efficacy of ruxolitinib.

Prevalence of depressive symptoms among adolescents / 预防医学

Objective To evaluate the prevalence of depressive symptoms and influencing factors among adolescents. Methods A total of 635 students aged 13 to 18 years were selected in March 2017 and were investigated with general information questionnaire, CES-D and CTQ-SF. Results 630 questionnaires are effective and the positive rate of depression was 29.84％(188/630) . The average score of CTQ was 32.15±2.98; 38.73％ of the students were disregarded and only 2.22％ of that were abused during their childhood. 40.00％ of the students had no CTQ, 1 kinds of CTQ accounted for 31.43％ , 2 kinds of CTQ accounted for 18.25％, and more than 3 CTQ accounted for 10.32％. Multivariate logistic regression analysis show that gender (OR=1.034, 95％ CI: 1.012-1.056) , parents' marital status (OR=1.124, 95％ CI: 1.087-1.162) , family atmosphere (OR=1.025, 95％ CI: 1.024-1.158) , CTQ cumulative number (ORCTQ=1=1.528, 95％ CI: 1.214-1.923; ORCTQ=2=3.067, 95％ CI: 1.325-7.102; ORCTQ≥3=10.361, 95％ CI: 3.059-35.093) were the risk factors for depression. Conclusion Gender, parents' marital status, family atmosphere and CTQ cumulative number were risk factors for depression in adolescents.

Effect of Over-Expression of KLF4 on the Proliferation and Apoptosis of K562 Cells In Vitro / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To study the effect of over-expression of KLF4 on the proliferation and apoptosis of K562 cells.</p><p><b>METHODS</b>The recombinant plasmid with over-expression of KLF4 was transfected into K562 cells by electroporation, then the obtained G418-resistant clones of K562 cells (K562/pEGFP-KLF4) were used as experimental group, and the vector control (K562/pEGFP-C1) and blank K562 cell control groups were set up at the same time. The expression of EGFP-KLF4 fusion protein in K562 cells was observed by fluorescence microscopy; the Western blot was performed to detect the level of KLF4 protein in the cells of each groups, the cell proliferation was tested by methylthiazolyl tetrazolium (MTT) assay, and the cell apoptosis was detected by flow cytometry.</p><p><b>RESULTS</b>Compared with K562/pEGFP-C1 group and blank K562 group, the level of KLF4 protein of K562/ pEGFP-KLF4 cells were significantly increased, and the over-expression ratio reached 74.07%(P<0.05). The proliferation ability of the over-expressing KLF4 K562 cells was inhibited significantly (P<0.05). However, the apoptosis of K562/pEGFP-ILK cells with over-expression of KLF4 was increased (P<0.05).</p><p><b>CONCLUSION</b>A stable over-expressing KLF4 protein K562 cell line with was constructed successfully, and the over-expression of KLF4 can inhibi proliferation and promote apoptosis of K562 cells.</p>

Effects and cost of four formulations of niclosamide ethanolamine salt in On-comelania hupensis snail control in field / 中国血吸虫病防治杂志

Objective To investigate the effects and cost of four formulations of niclosamide ethanolamine salt in Oncomela-nia hupensis snail control in the field in marshland and lake regions,so as to provide the evidence for drawing up the plan of mol-luscicide using in schistosomiasis endemic areas. Methods One drainage channel and one channel without water in the same area with snails in Jiangling County,Jingzhou City were selected as the research fields. The drainage channel was divided into 9 sections,except one section as a blank control group where the natural death rate of snails was observed only,and the remaining 8 sections were taken as the observation groups,where different dosages of 4％niclosamide ethanolamine salt powder,5％ni-closamide ethanolamine salt granules,25％ niclosamide ethanolamine salt suspending agent,26％ metaldehyde and ni-closamide ethanolamine salt suspending agent,and 50％niclosamide ethanolamine salt wettable powder were used re-spectively. The channel without water were divided into 4 sections,except one section as a blank control group,the oth-er 3 segments were taken as the observation groups,where 4％niclosamide ethanolamine salt powder,5％niclosamide ethanolamine salt granules,and 50％ niclosamide ethanolamine salt wettable powder were used respectively. Before and after spraying molluscicide for 7 days and 15 days,the system sampling method was used to observe the effects of snail control. Meanwhile,the unit cost method was used to calculate the costs of the different mulluscicide formulations abovementioned in unit area(1 m2). Results In the field at the drainage channel,the snail mortality rates of the groups spraying 4％niclosamide ethanolamine salt powder(50 g/m2),5％niclosamide ethanolamine salt granules(40 g/m2),25％ niclosamide ethanolamine suspending agent,26％ metaldehyde and niclosamide ethanolamine salt sus-pending agent,and 50％niclosamide ethanolamine salt wettable powder(2 g/m2 and 4 g/m2)for 7 days were 79.52％-97.87％,while the rates after spraying for 15 days were 71.00％-96.30％,and compared with those before spraying, the differences were statistically significant(all P<0.01). For the groups spraying with 2 g/m2 or 4 g/m2 suspending agent as well as wettable powder for 7 days,the snail mortality rates were significantly different(both P<0.05). In the field at the channel without water,the snail mortality rates of the 3 observation groups after spraying molluscicide for 7 days were 97.14％-100％,while for 15 days were 94.32％-100％,and compared with the rates before spraying,all the differences were statistically significant(all P<0.01). The unit costs per 1 m2 of the molluscicide abovementioned were ranged from 0.280 Yuan to 0.416 Yuan. Conclusions In marshland area inside embankment,the molluscicide formulations of the powder and granule are suitable for the environments without water or with instability water level , while the molluscicide formulations of the suspended agents and wettable powder are suitable for the water environment. Though the unit cost of powder is the lowest,the molluscicide in this formulation flies away seriously.

Mechanism of colon cancer cell apoptosis induced by telocinobufagin: role of oxidative stress and apoptosis pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of telocinobufagin on viability and apoptosis of colorectal cancer (CRC) cells and explore the mechanism of telocinobufagin-induced apoptosis.</p><p><b>METHODS</b>MTT assay was performed to detect the viability of CRC cells exposed to telocinobufagin. Nuclear staining with Hoechst 33342 and flow cytometry were used to analyze the cell death of CRC cells. Expressions of proteins related with cell apoptosis and oxidative stress were determined with Western blotting.</p><p><b>RESULTS</b>Telocinobufagin decreased the viability of CRC cells in a time- and dose-dependent manner. The presence of karyopycnosis and apoptotic bodies together with the results of flow cytometry suggested that telocinobufagin induced cell apoptosis to cause cell death. Western blotting showed that telocinobufagin exposure of the cells resulted in upregulated p53 and Bax protein expressions and promoted cleavage of caspase 9 and PARP. Telocinobufagin induced phosphorylation of Bad and PARP cleavage, and suppressed phosphorylation of IKBα and TAK1 and expression of survivin in the cells.</p><p><b>CONCLUSION</b>Telocinobufagin can decrease the viability of CRC cells by inducing cell apoptosis, which involves p53-mediated Bax activation and inhibition of the IAP pathway.</p>

Micro electrochemical mechanism of baicalin-metal complexes binding with hepatoma SMMC-7721 cell DNA / 中草药

Objective: The correlation of baicalin-metal (Y3+, La3+, and Ce3+) complexes (BMC) anti-tumor activity and the interactional ability of BMC binding with hepatoma SMMC-7721 cell DNA was investigated. Methods: Hepatoma SMMC-7721 cells DNA was extracted as a target, cyclic voltammetry and AC impedance were utilized to study the interaction between BMC and DNA, and the interaction mechanism between BMC and DNA was explored. Results: BMC and hepatoma SMMC-7721 cell DNA formed a non-electroactive supramolecular compounds through mixed-mode of electrostatic interaction, binding number m = 1, binding constant βBC = 1.27 × 105 L/mol, βBC-Y = 3.46 × 105 L/mol, βBC-La = 6.24 × 105 L/mol, and βBC-Ce = 7.29 × 106 L/mol. After BC binding with metal ions, its ability of binding to DNA significantly enhanced, and the strength order: BC-Ce > BC-La > BC-Y > BC. Conclusion: The ability of BMC binding with DNA consists with its cytotoxicity. After BMC binding with SMMC-7721 cell DNA, it could inhibit the cell proliferation and lead to the cell apoptosis, which illustrates the BMC exhibits an anti-tumor activity. The relevant results have given a reference for the study on the new anti-tumor complexes of Chinese materia medica.

The molecular mechanism between baicalin metal complexes and bovin serum album / 药学学报

In this paper, the new carbon nanotube modified glassy carbon electrode (F-CNTs/GCE) was prepared to establish a new method for studying the molecular interaction mechanism between baicalin metal complexes (BMC) and bovine serum album (BSA), and the principle of this method was discussed deeply. Under the physiological condition, the thermodynamics and kinetics properties of interaction between BMC and BSA were studied by cyclic voltammetry (CV) to inference their molecular effective mechanism. The results show that the presence of F-CNTs can accelerate the electron transfer, and better response signal was showed in the BMC/BMC-BSA system. The detection of interaction of BMC-BSA used new method show that BMC-BSA generates stable thermodynamically non-covalent compounds, and the obtained average binding sites of BMC-BSA were 1.7; the number of electron transfer in BMC/BMC-BSA reaction process was 2, and non electroactive supramolecular compounds of BMC-BSA were generated by this interacting reaction. The relevant research work provides a new way to study the molecular mechanism for the interaction of drugs with protein, and with a certain reference value for discussion on the non covalent interactions.

The molecular mechanism between baicalin metal complexes and bovin serum album / 药学学报

In this paper, the new carbon nanotube modified glassy carbon electrode (F-CNTs/GCE) was prepared to establish a new method for studying the molecular interaction mechanism between baicalin metal complexes (BMC) and bovine serum album (BSA), and the principle of this method was discussed deeply. Under the physiological condition, the thermodynamics and kinetics properties of interaction between BMC and BSA were studied by cyclic voltammetry (CV) to inference their molecular effective mechanism. The results show that the presence of F-CNTs can accelerate the electron transfer, and better response signal was showed in the BMC/BMC-BSA system. The detection of interaction of BMC-BSA used new method show that BMC-BSA generates stable thermodynamically non-covalent compounds, and the obtained average binding sites of BMC-BSA were 1.7; the number of electron transfer in BMC/BMC-BSA reaction process was 2, and non electroactive supramolecular compounds of BMC-BSA were generated by this interacting reaction. The relevant research work provides a new way to study the molecular mechanism for the interaction of drugs with protein, and with a certain reference value for discussion on the non covalent interactions.

Treatment of displaced humeral supracondylar fractures in children with external fixation using plaster or splint / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the therapeutic effects of closed reduction and external fixation (plaster or splint) for the treatment of displaced humeral supracondylar fractures in children.</p><p><b>METHODS</b>From March 2007 to September 2009,33 children (15 female and 18 male) with humeral supracondylar fractures treated in our hospital, ranging from 3 to 12 years old with an average of 6.4 years old. All the fractures were extension-type injuries, the flexion injures were excluded in our study. The humeral supracondylar fractures were classified according to Gartland classification. There were 21 Type H and 12 type III. In the initial treatment, all the patients were treated with closed reduction and external immobilization. The blood supply of the damaged upper extremity was evaluated before and after treatment. Clinical assessment was obtained at final follow-up using Flynn criteria, and radiologic assessment was obtained using Baumann and lateral humerocapitellar angles.</p><p><b>RESULTS</b>All the children were treated successfully with closed reduction in the initial time; 24 children maintained limb alignment by external immobilization. Nine patients lost position due to the swelling around the elbow which affected unstable external fixation during the follow-up, 5 of which were treated with a repeated closed reduction and internal fixation with Kirschner wires, 4 of which were treated with traction. Thirty-one patients had a satisfactory outcome and 2 patients had an unsatisfactory outcome according to the Flynn criteria at the latest follows-up.</p><p><b>CONCLUSION</b>Closed reduction and external stabilization is an important method for the treatment of displaced humeral supracondylar fractures in children. Making regular follow-up visits after closed reduction and casting is important for patients to maintain acceptable alignment, avoid complications and diagnose any loss of reduction.</p>

Effects of B.adolescentis and L.acidophilus in treating experimental ulcerative colitis in mice and their potential mechanisms / 中华消化杂志

Objective To investigate the effects of B.adolescentis and L.acidophilus in treatment of dextran sulphate sodium (DSS)-induced ulcerative colitis(UC) in mice and their potential mechanisms. Methods Seventy-five BABL/C mice were randomly divided into control,saline (NS),B.adolescentis BF0624 treatment (B),L.acidophilus LT0637 treatment (L) and salicylazosulpha-pyridine treatment (S) groups.Except control group,the other four groups were received DSS to induce ulcerative colitis. The weight-loss,fecal trait and bleeding were recorded every day.Colonic length and histological scores were evaluated on day 3,5 and 7.The gene and protein expression of hot shock protein (HSP)70, glucocorticoid receptor (GR),interleukin (IL)-10 and tumor necrosis factor (TNF)-α were detected by Western blot and reverse polymerase chain reaction (RT-PCR) respectively.Results B.adolescentis BF0624 and L.acidophilus LT0637 could relieve the inflammatory reaction of the experimental UC.The DAI scores were 1.84±0.4 in L group on day 3,which was lower than that in NS group (2.8±1.0).The DAI scores in all treatment groups were decreased on day 5.Compared with NS group[(8.1±0.6)cm ], the colon length on day 8 were (9.0±0.6)cm in B group,(9.35±0.6)era in L group and (8.8±1.1)cm in S group (P＜0.05).The colonic mucosa was improved pathohistologically in L group (6.0±1.0) on day 8.The expression of HSP70 and IL-10 in B and L groups were up-regulated and the expression of TNF-α was down-regulated.Conclusions Both B.adolescentis BF0624 and L.acidophilus LT0637 were effective in treatment of acute ulcerative colitis.The potential mechanism of two probiotics may be related with up-regulation of HSPT0 and IL-10 expressions and down-regulation of TNF-α expression.

Comparison percutaneous cervical disc nucleoplasty and cervical discectomy for the treatment of cervical disc herniation / 中华外科杂志

<p><b>OBJECTIVE</b>To compare the therapeutic effect of percutaneous cervical disc nucleoplasty (PCN group) and percutaneous cervical discectomy (PCD group) for the treatment of cervical disc herniation.</p><p><b>METHODS</b>A retrospective study was carried out from July of 2002 to December of 2004, and there were 80 cervical disc herniation cases who were operated by PCN (42 cases) or PCD (38 cases). The time of operation, clinical result and the stability of cervical spine after operation were evaluated and compared between 2 groups.</p><p><b>RESULTS</b>All cases had been followed up from 6 months to 26 months, average (12 +/- 5) months on the PCN group and (12 +/- 4) months on the PCD group, and there was no significant difference on 2 groups (t = -0.06, P = 0.953). All cases had been successfully operated. There was significant difference in the operation time between 2 groups (t = -21.70, P = 0.000). There was significant difference in the pre- and post-operation scores of each group (PCN group: t = 14.05, P = 0.000; PCD group: t = -14.79, P = 0.000). There was no significant difference in 2 groups of the clinical outcomes (z = -0.377, P = 0.706, > 0.05). There was no instability of cervical spine cases in 2 groups after operation (P > 0.05), and the cervical spine stability was no significant difference in pre- and-operation in each group.</p><p><b>CONCLUSIONS</b>PCN and PCD for the treatment of cervical disc herniation achieves good outcomes and no difference on the stability of cervical spine. PCN and PCD is a safe, minimally invasive, short time of operation, less traumatic operation and excellent clinical outcome.</p>