[Relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging and perioperative hemodynamic instability].

Objective: To analyze the relationship between carotid atherosclerotic plaque characteristics in magnetic resonance imaging (MRI) and perioperative hemodynamic instability in patients with severe carotid artery stenosis undergoing carotid artery stenting (CAS). Methods: A total of 89 patients with carotid artery stenosis who underwent CAS treatment at Beijing Tsinghua Changgung Hospital affiliated to Tsinghua University from January 1, 2017, to December 31, 2021, were prospectively included. Among them, 74 were male and 15 were female, with an age range of 43 to 87 years (mean age: 67.8±8.2 years). Preoperative examinations included carotid artery MRI vessel wall imaging to analyze the existence of large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and fibrous cap rupture in carotid artery plaques. Plaques without the above-mentioned risk factors were defined as stable plaque group (34 cases), while those with such risk factors were defined as vulnerable plaque group (55 cases). The number of risk factors present in each plaque was also calculated. Intraoperative changes in blood pressure and heart rate were recorded, and the use of dopamine postoperatively was noted. Using the risk factors that the plaque has as independent variables and the clinical outcomes as dependent variables, the RR values were calculated, and the differences in clinical outcomes of patients with different risk factors were compared. Results: The incidence rates of hypotension and bradycardia were higher in patients with vulnerable plaques than those with stable plaques (60.0% (33/55) vs 14.7%(5/34) and 38.2%(21/55) vs 14.7%(5/34), respectively; both P<0.05). Based on MRI imaging features, the large LRNC was present in 45 cases, with RR values for hypotension and bradycardia of 3.15 (1.69-5.87) and 2.20 (1.07-4.53), respectively; IPH was present in 37 cases, with RR values for hypotension and bradycardia of 2.70 (1.61-4.55) and 2.25 (1.15-4.39), respectively; and fibrous cap rupture was present in 29 cases, with RR values for hypotension and bradycardia of 1.50 (0.94-2.40) and 1.29 (0.67-2.49), respectively. The higher the number of risk factors in vulnerable plaques, the higher the incidence of intraoperative blood pressure and heart rate decrease: when the number of risk factors ranged from 0 to 3, the incidence of blood pressure decrease was 14.7% (5/34), 9/18, 11/18, and 13/19, respectively (P<0.001), and the incidence of heart rate decrease was 14.7% (5/34), 6/18, 7/18, and 8/19, respectively (P=0.022). There was no significant difference in the number of cases of dopamine use between the two groups (P>0.05). Conclusion: Patients with a higher number of risk factors for vulnerable carotid plaques, as indicated by carotid artery MRI vessel wall imaging, are at a higher risk of experiencing blood pressure and heart rate decrease during CAS surgery.

[Outcome of surgical repair for aortic coarctation with coexisting descending aortic aneurysm in adult patients].

Objective: To evaluate the efficacy of surgical treatment of aortic coarctation combined with descending aortic aneurysm in adult patients. Methods: This is a retrospective cohort study. Adult patients with aortic coarctation who were hospitalized in Beijing Anzhen Hospital from January 2015 to April 2019 were enrolled. The aortic coarctation was diagnosed by aortic CT angiography, and the included patients were divided into the combined descending aortic aneurysm group and the uncomplicated descending aortic aneurysm group based on descending aortic diameter. General clinical data and surgery-related data were collected from the included patients, and death and complications were recorded at 30 days after surgery, and upper limb systolic blood pressure was measured in all patients at discharge. Patients were followed up after discharge by outpatient visit or telephone call for their survival and the occurrence of repeat interventions and adverse events, which included death, cerebrovascular events, transient ischemic attack, myocardial infarction, hypertension, postoperative restenosis, and other cardiovascular-related interventions. Results: A total of 107 patients with aortic coarctation aged (34.1±15.2) years were included, and 68 (63.6%) were males. There were 16 cases in the combined descending aortic aneurysm group and 91 cases in the uncomplicated descending aortic aneurysm group. In the combined descending aortic aneurysm group, 6 cases (6/16) underwent artificial vessel bypass, 4 cases (4/16) underwent thoracic aortic artificial vessel replacement, 4 cases (4/16) underwent aortic arch replacement+elephant trunk procedure, and 2 cases (2/16) underwent thoracic endovascular aneurysm repair. There was no statistically significant difference between the two groups in the choice of surgical approach (all P>0.05). In the combined descending aortic aneurysm group at 30 days after surgery, one case underwent re-thoracotomy surgery, one case developed incomplete paraplegia of the lower extremity, and one case died; and the differences in the incidence of endpoint events at 30 days after surgery were similar between the two groups (P>0.05). Systolic blood pressure in the upper extremity at discharge was significantly lower in both groups compared with the preoperative period (in the combined descending aortic aneurysm group: (127.3±16.3) mmHg vs. (140.9±16.3) mmHg, P=0.030, 1 mmHg=0.133 kPa; in the uncomplicated descending aortic aneurysm group: (120.7±13.2) mmHg vs. (151.8±26.3) mmHg, P=0.001). The follow-up time was 3.5 (3.1, 4.4) years. There were no new deaths in the combined descending aortic aneurysm group, no transient ischemic attack, myocardial infarction or re-thoracotomy surgery, and one patient (1/15) suffered cerebral infarction and 10 patients (10/15) were diagnosed with hypertension. The differences in the occurrence of endpoint events during postoperative follow-up were similar between the two groups (P>0.05). Conclusion: In experienced centers, long-term prognosis of patients with aortic coarctation combined with descending aortic aneurysm is satisfactory post surgical intervention.

[The value of a nomogram based on clinical data and contrast enhanced CT radiomics in the preoperative prediction of Epstein-Barr virus-associated gastric carcinoma].

Objective: To explore the value of a nomogram based on clinical data and enhanced CT radiomics in the prediction of Epstein-Barr virus-associated gastric carcinoma(EBVaGC). Methods: The data of 136 patients, including 100 males and 36 females, aged [M (Q1, Q3)] 65 (53, 71) years, with gastric cancer confirmed by surgery and pathology were retrospectively analyzed. According to Epstein-Barr virus-encoded small RNA (EBER) in situ hybridization, those patients were divided into Epstein-Barr virus (EBV) positive group (n=32) and EBV negative group (n=104). All patients underwent multi-phase enhanced CT scanning before surgery and randomly assigned to the training group (n=95) and validation group (n=41) in a ratio of 7︰3. MaZda software was used to extract radiomics features of enhanced CT images. The intra-group correlation coefficient (ICC), variance analysis and minimum absolute shrinkage and selection algorithm (LASSO) regression were used to reduce the dimensionality of the radiomics features, and then the radiomics score (Radscore) was calculated. The nomogram model was based on combined clinical data, morphological features and Radscore. The predictive power of the nomogram was evaluated according to the area under the receiver operating characteristic curve (AUC), and the net clinical benefit of the nomogram was evaluated by the decision curve and calibration curves were drawn according to the data of the training group and the validation group to analyze the consistency of the nomogram model. Results: After selection, six optimal radiomics features were obtained, including Mean, Skewness, S(1, 0) Sum entropy, S(1, 1) Contrast, 99% percentile and S(2, 2)Angular second moment. Radscore of EBV positive group were higher than that of the EBV negative group (training group: 3.78±0.83 vs 2.80±0.98; validation group: 3.81±0.47 vs 2.94±0.95) (both P<0.05) both in the training group and validation group. The AUC of the radiomics model in training group and validation group were 0.773(95%CI:0.612-0.962)and 0.792(95%CI:0.597-0.927)respectively,and the sensitivity and specificity were 63.6% and 93.1%, 70.0% and 87.1%, respectively. The AUC of the nomogram model based on clinical data and radiomics in the training group and the validation group were 0.883(95%CI:0.644-0.984) and 0.851(95%CI:0.715-0.996), respectively. The nomogram model showed superior predictive performance (both P<0.05). Conclusion: The nomogram model based on clinical data and radiomics has better efficacy in the prediction of Epstein-Barr virus associated gastric cancer.

[Comprehensive treatment of 25 cases of acute necrotizing fasciitis].

From May 2013 to March 2020, 25 patients with acute necrotizing fasciitis were admitted to Beijing Chaoyang Emergency Rescue Center, including 18 males and 7 females, aged 7 to 78 years. The lesions were mainly located in the lower extremities, with the original lesion areas ranging from 20 cm×15 cm to 83 cm×42 cm. After admission, comprehensive systemic treatment was performed, the lesion area was cut open and drained as soon as possible, and the necrotic tissue was removed. Vacuum sealing drainage was performed when the necrotic tissue in the wound was reduced. The wounds were directly sutured or repaired with thin split-thickness skin grafts taken from head and/or thigh or local skin flaps after the wounds were improved. The skin grafts and flaps survived well after surgery, and the wound was completely closed. None of the 25 patients had amputation. A total of 21 patients were followed up for more than half a year, showing no recurrence of acute necrotizing fasciitis and no difference in the function of their injured limb after the wound healing than before the onset.

Long noncoding RNA MIAT promotes the growth and metastasis of non-small cell lung cancer by upregulating TDP43.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "Long noncoding RNA MIAT promotes the growth and metastasis of non-small cell lung cancer by upregulating TDP43, by H.-L. Zhao, S.-Q. Xu, Q. Li, Y.-B. Zhao, X. Li, M.-P. Yang, published in Eur Rev Med Pharmacol Sci 2019; 23 (8): 3383-3389-DOI: 10.26355/eurrev_201904_17702-PMID: 31081093" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/17702.

[Feasibility and efficacy of percutaneous closure of paravalvuar leak in patients after heart valve replacement surgery using Amplatzer vascular plug â ¢].

Objective: To investigate the feasibility and efficacy of percutaneous closure of paravalvuar leak (PVL) in patients after heart valve replacement surgery using Amplatzer vascular plug Ⅲ (AVP Ⅲ). Methods: In this retrospective study, consecutive PVL patients after heart valve replacement surgery receiving percutaneous closure with AVP Ⅲ in Beijing Anzhen hospital between March 2017 and October 2018 (n=21) were enrolled.The preoperative and intraoperative data and short-and mid-term outcome results were analyzed. Results: Theage of patients in this cohort was (54.9±11.7) years, and there were 12 (57.1%) male patients. There were 8 patients (38.1%) post mitral valve replacement, 4 patients (19.0%) post aortic valve replacement and 9 patients (42.9%) post double valves replacements.There were 14 cases (66.7%) of mitral valve PVL,6 cases (28.6%) of aortic valve PVL, and 1 case (4.8%) of double valves PVL.Successful device deployment was accomplished in 18 defects from 17 PVL patients. Technical successful rate of mitral valve PVL closure and aortic valve PVL closure was 12/15 and 6/7,respectively. One patient received surgical repair due to procedure-induced femoral pseudoaneurysm.There were 17 cases of severe PVL and 1 case of moderate PVL before procedure, and there were 2 cases of moderate PVL, 6 cases mild PVL, and PVL disappeared in 10 cases after procedure (P<0.01 vs. pre-procedure). The follow-up time was (8.3±4.7) months. There were 10 cases (58.8%) of New York Heart Association (NYHA) function grade Ⅲ and 7 cases (41.2%) of NYHA function grade Ⅳ before procedure, and there were 12 cases of NYHA function grade Ⅰ(70.6%) and 5 cases (29.4%) of NYHA function grade Ⅱ post procedure (P<0.01). Post procedure, there was no displacement of the occluder and heart valve movement was not affected,and there was no new hemolysis or hemolysis worsening. Conclusion: Percutaneous closure of PVL in patients after heart valve replacement surgery with AVP Ⅲ is feasible, and associated with favorable short-and mid-term clinical outcomes.

Long noncoding RNA MIAT promotes the growth and metastasis of non-small cell lung cancer by upregulating TDP43.

OBJECTIVE: Recent researches have proved that long noncoding RNAs (lncRNAs) act and have an important role in many diseases. In this research, lncRNA MIAT was explored to identify how it functions in the development of non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was utilized to detect MIAT expression in NSCLC patients. Next, we conducted cell counting kit-8 (CCK-8) assay, colony formation assay, ethynyl deoxyuridine (EdU) incorporation assay, wound healing assay and transwell assay to identify its biological function. Further experiments were performed to explore the potential mechanism. RESULTS: By comparing with MIAT expression in adjacent tissues, MIAT expression level was significantly higher in NSCLC samples. Moreover, functional assays showed that cell growth ability of NSCLC cells was inhibited after MIAT was knocked down. In addition, the migrated and invaded ability of NSCLC cells was inhibited after MIAT was knocked down. Furthermore, the expression of TDP43 was downregulated by knockdown of MIAT. Meanwhile, it was found that TDP43 expression positively correlated to MIAT expression in NSCLC tissues. CONCLUSIONS: Results above suggest that MIAT could enhance cell proliferation and metastasis of NSCLC by upregulating TDP43, which suggests that MIAT may be a potential therapeutic target in NSCLC.

[The analysis of mutations in non-syndromic deafness gene SLC26A4 by next generation sequencing technology].

Objective:To analogize the distribution of nonsyndromic deafness gene SLC26A4 mutation and to characterize clinical profiles in patients with SLC26A4 mutation in order to understand their hereditary etiologies and provide evidence for deafness screening and accurate genetic counseling. Method: SLC26A4 gene was first analized by MALDI-TOF-MS technology to detect the hot mutation c.919-2A>G in 57 cases. There were 3 cases with homozygous mutation and 7cases with heterozygous mutation. Then 54 cases except for 3 cases with homozygous mutation were analyzed by targeted genomic capturing and next generation sequencing technologies(targeted DNA-Hiseq), 81 non-syndromic deafness genes and the chondiogene was designed to all their exons and their flanking intron(±10 bp) sequences. Sanger sequencing was used to confirm the variant by analyzing the DNAs sequences. Result: The carrying rates of SLC26A4 gene in the deafness were 26.32%, but SLC26A4 homozygous genes and compound heterozygous genes were 19.30%. They included 3 cases with c.919-2A>G and 1 case with c.754T>C pathogenic homozygous mutations. While in 7 cases with compound heterozygous there were 6 cases with two pathogenic mutation, there was 1 case with c.2168A>G pathogenic mutation the other likely pathogenic mutation c.1545-1546insC. The 11 cases all were diagnosed large vestibular aqueduct syndrome(LVAS). There were 4 cases with heterozygous that were not found large vestibular aqueduct. Conclusion: Pathogenic mutation of SLC26A4 is closely related to clinical phenotype of LVAS. The hot pathogenic mutation was c.919-2A>G of SLC26A4 gene. The next generation sequencing technology is available for the diagnosis of inherited hearing loss especially for LVAS.

[Dynamic features of tumefactive demyelinating lesions in different clinical stages by contrast-enhanced magnetic resonance imaging].

Objective: To explore the dynamic features of tumefactive demyelinating lesions (TDLs) in different clinical stages by contrast-enhanced magnetic resonance imaging (MRI). Methods: Thirty-five patients with TDLs proven by pathological studies were prospectively recruited from January 2015 to January 2017.Brain contrast-enhanced MRI of the patients in different clinical stages including acute phase, subacute phase and chronic phase were completed after enrollment.The characteristics of contrast-enhanced MRI in different clinical stages were compared and the evolutional characteristics were summarized. Results: (1) Acute phase (35/35): the patterns of enhancement were patchy (74.3%, n=26), nodule (34.3%, n=12), closed ring (14.3%, n=5) and open ring (11.4%, n=4). (2) Subacute phase (32/35): the patterns of enhancement were open ring (40.6%, n=13), closed ring (31.3%, n=10), patchy (25.0%, n=8) and irregular edge of enhancement (21.9%, n=7). (3) Chronic phase (15/35): the patterns of enhancement were pale patchy (10/15), open ring (5/15) and closed ring (2/15). (4) The proportions of enhancement patterns including patchy, nodule, edge enhancement and pale patchy were significantly different among different clinical stages: ① The patchy and nodule were the more common enhancement patterns in acute phase. ② The edge enhancement was found mostly in subacute phase. ③ The pale patchy was found mostly in chronic phase. Conclusions: The manifestation of the lesions on contrast-enhanced MRI may have some characteristics of dynamic evolution according to different clinical stages.The dynamic observation may be helpful for the diagnosis and differential diagnosis of TDLs.

[Application of three-dimensional digital subtraction angiography on hepatic artery chemoembolization].

Objective: To explore the clinical value of 3D-DSA technology in the diagnosis and treatment guidance of hepatic artery chemoembolization. Methods: Liver cancer patients in the treatment groups were collected to receive 3D-DSA imaging guidance at the Affiliated Hospital of Xuzhou Medical University between March and May 2017. In addition, routine 2D-DSA imaging was selected for treatment-received group. Intra-operative blood vessels and tumor-like lesions were observed. The total exposure dose (CAK, unit mGy), cumulative irradiation intensity per unit area (DAP, unit mGy.cm2) and dosage of contrast agent (ml) were calculated separately for two groups of patients. The same senior physicians and technicians operated both groups of patients. Comparisons of measurement were analyzed by t-test and chi-square test was used for count data. Results: Data of twenty patients were collected from the two groups. Tumor location, target vessels structure and shape of development were clear in all patients in the treatment group. The control group had 17 cases of tumor development and the target vascular structure was clear in 16 cases. CAK mean treatment group was lower than control group (554.11 + 38.87) mGy and (644.53 + 26.70) mGy, and DAP mean treatment group was lower than the control group (125.25 + 7.54) mGy·cm(2) and (143.49 + 6.18) mGy·cm(2). The two groups were compared (P value < 0.05), and the differences were statistically significant. The mean dose of contrast agent in the two groups were lower than control group (64.42 + 3.92) ml, (70.79 + 4.47) ml, and the differences between the two groups were statistically significant (P < 0.05). Conclusion: 3D-DSA imaging technology can provide effective diagnosis and guidance in the treatment of hepatic artery chemoembolization. It can effectively reduce the radiation exposure dose and radiation intensity, and it is of high clinical value for interventional embolization of liver cancer.

[Problems and suggestions for the application of diagnosis-related groups system in burn surgery].

The diagnostic codes of diagnosis-related groups system used in our country are different from the clinical diagnostic criteria of burns. The author suggests that the diagnostic codes should be improved according to clinical criteria in terms of the total area and depth of burns and inhalation injury, and the diagnosis of burns with related special causes and sites should be added to the clinical criteria.

Protease-activated receptor-2 suppresses interleukin (IL)-10 expression in B cells via upregulating Bcl2L12 in patients with allergic rhinitis.

BACKGROUND AND AIMS: The function of interleukin (IL)-10-producing B cells (B10 cell) is compromised in patients with allergic diseases. Protease-activated receptor (PAR)-2 has immunoregulatory functions. This study aimed to elucidate the role of PAR2 in the suppression of IL-10 expression in peripheral B cells. METHODS: Peripheral blood B cells were collected from patients with allergic rhinitis (AR). A correlation between the expression of Bcl2-like protein 12 (Bcl2L12) and IL-10 in the B cells was analyzed. An AR mouse model was developed. RESULTS: We observed that the expression of IL-10 was lower in the peripheral B cells from patients with airway allergy. A negative correlation was identified between the expression of IL-10 and PAR2 in B cells. Activation of PAR2 of B cells increased the expression of Bcl2L12 and suppression of LPS-induced IL-10 expression, which were inhibited by knocking down the Bcl2L12 gene. Treating B cells from AR patients with Bcl2L12-shRNA-carrying liposomes reversed the capability of IL-10 expression and the immunosuppressive function. Administration of Bcl2L12 shRNA-carrying liposomes attenuated experimental AR in mice. CONCLUSIONS: Activation of PAR2 inhibits the expression of IL-10 in B cells, which can be reversed by treating B cells with Bcl2L12 shRNA-carrying liposomes. The data suggest that regulation of Bcl2L12 may be a novel approach in the treatment for AR.

[The correlation between CT score of lung injury and oxygenation index in patients with acute hydrogen sulphide poisoning].

Objective: To explore correlation between chest CT score and oxygenation index in patients with acute hydrogen sulphide poisoning, whether CT score can be applied to assess acute lung injury after acute hydrogen sulfide poisoning and provide basis and reference. Methods: The clinic and a series of CT datas of 32 acute hydrogen sulphide poisoning cases were retrospectively analysed and compared, According to GBZ31-2002 (the diagnostic standard of occupational H(2)S acute poisoning) , these patients were divided into 2 grouds including moderate groud and severe groud; The CT score were improved, referenceing the scoring criteria of the chest X-ray; The difference of the CT score and the oxygenation index were analyzed between moderate and severe group in the acute phase and the disperse phase; The correlation between CT score and oxygenation index were analyzed. Results: The CT score in moderate poisoning group were lower than severe group (2.26±1.37 vs 10.44±2.55, 1.34±0.65 vs 4.55±2.45, all P<0.05) in the acute phase and the dissipation phase.The oxygen index of the 19 cases in the acute phase were 307.55±28.29, and the oxygen index of the 8 cases in the dissipation phase was 435.75±37.00; The oxygen index of the 9 cases in the acute phase and the dissipation phase were respectively 193.17±36.41, 347.67±44.49. The oxygen partial pressure and oxygenation index in severe group were significantly lower than those in moderate group (all P<0.01) in the acute phase and the dissipation phase. Pearman correlation analysis showed that the CT score were negatively correlated to the oxygen index in the acute phase and the dissipation phase, respectively (r=-0.97、-0.75, all P<0.01) . Conclusions: The CT score of lung injury and oxygenation index is negatively correlated. The CT score can be used to evaluate the degree of lung injury, and can be used in the evaluation of acute lung injury after acute hydrogen sulfide poisoning.

[An analysis of the mutation in GJB2，GJB3，SLC26A4 and mtDNA12SrRNA in new born].

Objective:To analyze deafness gene mutation in GJB2，GJB3，SLC26A4 and mtDNA12SrRNA in newborn and to explore the significance of genetic test and potential correlations between the genotype and clinical phenotype.Method:Blood samples were collected with a standard protocol and DNA templates are extracted from 501 newborn in Longgang of Shenzhen.MALDI-TOF-MS Technology was used to detect the coding region twenty mutations sites of GJB2，GJB3，SLC26A4 AND mtDNA12SrRNA，includingSLC26A4(1226G>A,1229C>T,281C>T,589G>A,IVS7-2A>T,1174A>T,IVS15+5G>A,1975G>C,2027T>A,2162C>T,2168A>G),GJB2(176-191del16,35delG,167delT,235 delC,299-300 delAT),GJB3(547G>A,538C>T),mtDNA12SrRNA(1555A>G,1494C>T).While two-step hearing screening was carried by using AABR（automatedauditory brainstem response）and DPOAE. Result:In the 501 newborns,26 cases were found have one or two allele mutations of deafness-susceptibility genes.GJB2 gene mutation(n=9,1.796%) all were 235 delC single heterozygosity mutation.GJB3 gene mutation(n=3,0.599%). SLC26A4 gene mutation(n=12,2.395%) included IVS7-2A>G heterozygosity mutation(n=5). MtDNA 12Rrna gene mutation was found in 3 child(n=3,0.599%). Finally one of 26 infants was diagnosed enlarged vestibular aqueduct syndrome. The infant was detected 2168A>G heterozygosity mutation. Conclusion:235delC is the main mutation form of GJB2 gene,while it is the hottest mutation in People. But SLC26A4 gene mutations are the main type in newborn. MtDNA 12Rrna gene mutation was found in 3 child.This genetic epidemiological study demonstrated that genetic screening is helpful for determining high risk individuals and early discovering possible late-onset hearing loss. Moreover pationts and family member can acquire more effective genetic counseling.

PTPH1 promotes tumor growth and metastasis in human glioma.

OBJECTIVE: Glioma is the most common form of brain tumor, accounting for over 50% of all primary tumors. Despite progress in the treatment of glioma, the prognosis is still poor. In this study, we examined protein-tyrosine phosphatase H1 (PTPH1) in human gliomas. MATERIALS AND METHODS: Cell growth potential was measured by CCK-8 assay and colony formation. Cell cycle distribution was measured by flow cytometry. Transwell assay was used to detect the motility of tumor cells. Real-time PCR and Western blot were used to measure the mRNA and protein expression of indicated genes. Xenograft model was established to measure the role of PTPH1 in vivo. RESULTS: The expression of PTPH1 was significantly higher in the tumor tissues as compared with that in the adjacent normal tissues. Knockdown of PTPH1 significantly slowed cell proliferation and reduced colony formation abilities in glioma cell lines U87 and U251. Additionally, knockdown of PTPH1 caused cell cycle arrest in the S-phase. Furthermore, depletion of PTPH1 in glioma U87 cells significantly limited tumor growth in a xenograft model. Interestingly, knockdown of PTPH1 also decreased cell migration abilities in both U87 and U251 cells. Accordingly, matrix metalloproteinase 9 (MMP9) was also decreased upon knockdown of PTPH1 in both cell lines. Moreover, we found that phosphorylated MEK (p-MEK) and phosphorylated MAPK (p-MAPK) were both decreased, whereas the total levels of MEK and MAPK remained unchanged after depletion of PTPH1 in both cell lines. CONCLUSIONS: Our data suggest that PTPH1 may be a novel biomarker that indicates the aggressiveness of gliomas. Targeting PTPH1 might be a promising strategy for the treatment of gliomas.

MiR-181 family: regulators of myeloid differentiation and acute myeloid leukemia as well as potential therapeutic targets.

MicroRNAs have been shown to play an important role in normal hematopoisis and leukemogenesis. Here, we report function and mechanisms of miR-181 family in myeloid differentiation and acute myeloid leukemia (AML). The aberrant overexpression of all the miR-181 family members (miR-181a/b/c/d) was detected in French-American-British M1, M2 and M3 subtypes of adult AML patients. By conducting gain- and loss-of-function experiments, we demonstrated that miR-181a inhibits granulocytic and macrophage-like differentiation of HL-60 cells and CD34+ hematopoietic stem/progenitor cells (HSPCs) by directly targeting and downregulating the expression of PRKCD (which then affected the PRKCD-P38-C/EBPα pathway), CTDSPL (which then affected the phosphorylation of retinoblastoma protein) and CAMKK1. The three genes were also demonstrated to be the targets of miR-181b, miR-181c and miR-181d, respectively. Significantly decreases in the expression levels of the target proteins were detected in AML patients. Inhibition of the expression of miR-181 family members owing to Lenti-miRZip-181a infection in bone marrow blasts of AML patients increased target protein expression levels and partially reversed myeloid differentiation blockage. In the mice implanted with AML CD34+ HSPCs, expression inhibition of the miR-181 family by Lenti-miRZip-181a injection improved myeloid differentiation, inhibited engraftment and infiltration of the leukemic CD34+ cells into the bone marrow and spleen, and released leukemic symptoms. In conclusion, our findings revealed new mechanism of miR-181 family in normal hematopoiesis and AML development, and suggested that expression inhibition of the miR-181 family could provide a new strategy for AML therapy.

The role, mechanism and potentially therapeutic application of microRNA-29 family in acute myeloid leukemia.

Abnormal proliferation, apoptosis repression and differentiation blockage of hematopoietic stem/progenitor cells have been characterized to be the main reasons leading to acute myeloid leukemia (AML). Previous studies showed that miR-29a and miR-29b could function as tumor suppressors in leukemogenesis. However, a comprehensive investigation of the function and mechanism of miR-29 family in AML development and their potentiality in AML therapy still need to be elucidated. Herein, we reported that the family members, miR-29a, -29b and -29c, were commonly downregulated in peripheral blood mononuclear cells and bone marrow (BM) CD34+ cells derived from AML patients as compared with the healthy donors. Overexpression of each miR-29 member in THP1 and NB4 cells markedly inhibited cell proliferation and promoted cell apoptosis. AKT2 and CCND2 mRNAs were demonstrated to be targets of the miR-29 members, and the role of miR-29 family was attributed to the decrease of Akt2 and CCND2, two key signaling molecules. Significantly increased Akt2, CCND2 and c-Myc levels in the AML cases were detected, which were correlated with the decreased miR-29 expression in AML blasts. Furthermore, a feed-back loop comprising of c-Myc, miR-29 family and Akt2 were found in myeloid leukemogenesis. Reintroduction of each miR-29 member partially corrected abnormal cell proliferation and apoptosis repression and myeloid differentiation arrest in AML BM blasts. An intravenous injection of miR-29a, -29b and -29c in the AML model mice relieved leukemic symptoms significantly. Taken together, our finding revealed a pivotal role of miR-29 family in AML development and rescue of miR-29 family expression in AML patients could provide a new therapeutic strategy.

Small interfering RNA targeting nuclear factor kappa B to prevent vein graft stenosis in rat models.

BACKGROUND: Intimal hyperplasia plays an important role in vein graft stenosis. Inflammatory injury, especially nuclear factor kappaB (NF-κB) gene activation, is highly involved in stenosis progression. We examined whether neointimal hyperplasia and vein graft stenosis could be inhibited by silencing the NF-κB gene with small interference RNA (siRNA). METHODS: Sixty adult male Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft group, a scrambled siRNA group, and an NF-κB siRNA group. We performed reverse interpositional grafting of the autologous external jugular vein to the abdominal aorta. Vein grafts were treated with liposome and gel complexes containing NF-κB siRNA or scrambled siRNA. The levels of monocyte chemoattractant protein -1, tumor necrosis factor-α, and NF-κB p65 in vessel tissues were evaluated after surgery for content of proliferating cell nuclear antigen (PCNA) and vascular wall thickness. RESULTS: NF-κB siRNA treated vein graft showed less neointimal formation and fewer positive PCNA cells (P < .05). In addition there were lower levels of, NF-κB p65 protein and of inflammatory mediators (P < .05) compared with the vein graft group. CONCLUSION: Our study suggested that siRNA transfection suppressed NF-κB expression, reduced inflammatory factors, lessened neointimal proliferation, and suppressed PCNA.

Advanced malignant pleural or peritoneal effusion in patients treated with recombinant adenovirus p53 injection plus cisplatin.

The aim of this study was to evaluate the efficacy of recombinant adenovirus p53 agent (rAd-p53) injection combined with cisplatin (CDDP) for the treatment of malignant pleural or peritoneal effusion. After puncture drainage, patients in the treatment group (n = 27) received intracavitary administration of rAd-p53 (2 x 10(12) virus particles) once a week for 4 weeks. At 48 h after each rAd-p53 injection, patients were given intracavitary administration of cisplatin 60 mg/m(2). This administration procedure continued once a week for 4 weeks. The control group (n = 21) received the same intracavitary therapy as the treatment group but without rAd-p53 therapy. Efficacy was evaluated by clinical observations, computed tomography, tumour markers, Karnofsky score and short-term follow-up. The total effective rates for the treatment group (63.0%) were significantly higher than for the control group (42.9%), suggesting that the treatment group benefited over the control group. In conclusion, rAd-p53 therapy is a safe and effective treatment for advanced malignant pleural or peritoneal effusion.