OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

OBJECTIVE: To illustrate the molecular mechanisms underlying the therapeutic effects of electroacupuncture (EA) on knee osteoarthritis (OA). METHODS: Twenty-seven six-month-old New Zealand white rabbits were allocated into three groups in accordance with a random number table: normal group (no surgery-induced OA; without treatment), model group (surgery-induced OA; without treatment) and EA group [surgery-induced OA; received treatment with EA at acupoints Dubi (ST 35) and Neixiyan (EX-LE 5), 30 min twice a day]. After eight consecutive weeks of treatment, the histopathological alterations in cartilage were observed using optical microscopy and transmission electron microscopy, cartilage degeneration was evaluated by modified Mankin's score principles, the synovial fluid concentration of interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-3 (MMP-3) were evaluated by enzyme-linked immunosorbent assay, and the protein expression levels of IL-1β, IL-6, TNF-α, MMP-3, IκB kinase-β (IKK-β), nuclear factor of α light polypeptide gene enhancer in B-cells inhibitor α (IκB-α) and nuclear factor-κB (NF-κB) p65 were quantified by Western blot analysis. RESULTS: EA treatment significantly improved cartilage structure arrangement and reduced cellular degeneration. The IL-1β, IL-6, TNF-α and MMP-3 of synovial fluid in the EA-treated group were significantly decreased compared with the model group (all P<0.01). Compared with the model group, the IL-1β, IL-6, TNF-α, MMP-3, IKK-β and NF-κB p65 protein expressions in cartilage of EA-treated group were significantly decreased (all P<0.01), whereas IκB-α expression was significantly up-regulated (P<0.01). CONCLUSION EA treatment may delay cartilage degeneration by down-regulating inflammatory factors through NF-κB signaling pathway, which may, in part, explain its clinical efficacy in the treatment of knee OA.

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVE: To explore the toxicity of 1,2-dichloroethane( 1,2-DCE) and its metabolites on human astrocytes( HAs). METHODS: Different doses of 1,2-DCE( 5. 00,10. 00,25. 00,50. 00 and 100. 00 mmol/L),2-chlorohydrins( 5. 00,25. 00,50. 00,100. 00 and 200. 00 mmol/L),2-chloroacetaldehyde( 1. 00,5. 00,10. 00,20. 00 and 50. 00 mmol / L) and chloroacetic acid( 0. 01,0. 05,0. 10,0. 50 and 1. 00 mmol / L) were used for treating HAs in vitro during their logarithmic phase. After 24 hours of culture,the morphology of HAs was observed by fluorescent inverted phase contrast microscope. The survival rate and the inhibition ratio of HAs were detected by CCK-8 colorimetry to estimate the50% inhibiting concentration in 24 hours( 24 h-IC50). The apoptosis of HAs was tested by double-labeling and flow cytometry using Annexin Ⅴ-fluorescein isothiocyanate and propidium iodide. RESULTS: The morphology of HAs changed in varying degrees after 24 hours exposure to 1,2-DCE,2-chlorohydrins,2-chloroacetaldehyde and chloroacetic acid. The changes included smaller size of cells,pseudopodia tapering,increased intracellular particles and suspension of circular cells and decreased transparency of cells. With the increasing does of 1,2-DCE,2-chlorohydrins,2-chloroacetaldehyde and chloroacetic acid exposure,the survival rates of HAs decreased( P < 0. 01),while its inhibition ratios increased( P <0. 01). They all showed dose-effect relationship. 24 h-IC50 of the above 4 chemicals were 56. 25,235. 00,26. 43 and1. 38 mmol / L,respectively. The 1,2-DCE,2-chlorohydrins and chloroacetic acid could induce the apoptosis of HAs and the apoptosis rate of HAs was positively correlated with the 3 kinds of chemicals( P < 0. 01). CONCLUSION: 1,2-DCE and its metabolites 2-chloroacetaldehyde,2-chlorohydrins and chloroacetic acid can lead to toxic damage and induce the apoptosis of HAs. Chloroacetic acid has the strongest toxicity among the metabolites.

OBJECTIVETo study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL).

METHODSClinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups.

RESULTS(1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05).

CONCLUSIONHHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; therapeutic use ; Female ; Harringtonines ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; therapeutic use

OBJECTIVETo investigate biosynthetic and apoptotic mechanisms in repair of full thickness skin defect with collagen-chitosan porous scaffold transplantation, and to determinate differences between wound repair with the scaffold transplantation and scar healing without the scaffold transplantation.

METHODSThe full thickness skin defects were made on 10 Bama miniature pigs and the bilayer dermal equivalent (BDE) composed of collagen-chitosan porous scaffold and silicone membrane was transplanted on wounds. Surfaces of wounds were observed at 1, 2, and 3 weeks after the BDE transplantation, and so were done the wound repairs after epidermis had been grafted for 2 weeks on surface of the scaffold which had been transplanted on skin defect wounds for 2 weeks. At the same time, TGF-beta1 expressions, apoptosis and self collagen replacement of scaffolds in wounds were detected in situ by immunohistochemical staining, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) and picrosirius red polarized light. Wounds without scaffold transplantation were studied as control.

RESULTS1) Wounds with the scaffold transplantation were different from granulation tissue. 2) The peak of TGF-beta1 expression in the scaffold wounds was from 1 to 2 weeks after BDE transplantation, and TGF-beta1 expressions decreased continuously from 3 to 4 weeks. TGF-beta1 expressions increased continuously in the control wounds from 1 to 3 weeks and decreased on 4 weeks. TGF-beta1 expressions in the scaffold wounds on 1st and 2nd week were significantly higher than those in the corresponding control wounds, whereas, TGF-beta1 expressions in the scaffold wounds on 3rd and 4th week were significantly lower than those in the corresponding control wounds. 3) Apoptosis increased continuously in the scaffold wounds from 2 to 4 weeks after BDE transplantation, and so did in the control wounds from 3 to 4 weeks. However, apoptosis signals in the scaffold wounds on 2nd, 3rd, and 4th week after BDE transplantation were significantly more than those in the corresponding control wounds, and there was no difference between apoptosis signals in the scaffold wounds on 1st week after BDE transplantation and those in the corresponding control wounds. 4) Observation by picrosirius red polarized light method: self collagen began to synthesize in the scaffold wounds on 1st week after BDE transplantation, and scaffolds had been replaced by self collagen from 2 to 3 weeks after BDE transplantation.

CONCLUSIONSCollagen-chitosan porous scaffold plays a very important role in wound healing of full thickness skin defect. The mechanisms of wound repair by dermal scaffold are different from those by granulation and scar healing. It has a good future in repairing skin defect.

Animals ; Apoptosis ; Chitosan ; metabolism ; Collagen ; biosynthesis ; metabolism ; Dermis ; Extracellular Matrix ; Female ; Skin Irritancy Tests ; Skin, Artificial ; Stents ; Swine ; Swine, Miniature ; Tissue Engineering ; Transforming Growth Factor beta1 ; metabolism ; Wound Healing

OBJECTIVETo explore the effective skills of reconstruction and balance of soft tissue in hemi-shoulder replacement for patients with four-part fracture of the proximal humerus in order to avoid postoperative complications of joint instability and great tubercle displacement.

METHODSFrom June 2002 to June 2006, 25 patients with Neer four-part fracture of the proximal humerus were adopted in the study which included 15 females and 10 males, with the mean age of 66 years (ranged from 56 years to 80 years). They were treated with humeral head replacement and should joint reparation simultaneously by modified operation approach and reconstruction and balance skills of soft tissue.

RESULTSThe mean duration of follow-up was 2.3 years (ranged from 1 to 4.5 years). No infection, nerve damage and prosthesis loosing were found in all cases. Two cases of infra-forward dislocation or subluxation occurred due to affected limb placed on abduction splint postoperatively. One case occurred prosthesis upward displacement due to early active abduction exercise but no complains. Neither joint instability nor displacement and malunion of great tubercle were found in other patients. According to Neer scoring system, 6 cases were rated as excellent, 15 as good and 5 as fair. The good and excellent rate was 84%.

CONCLUSIONIn hemi-shoulder replacement for patients with Neer four-part fracture the modified operation approach and reconstruction and balance of soft tissue skills combined with rational rehabilitation exercise can prevent postoperative shoulder joint instability and displacement and malunion of great tubercle.

Aged ; Aged, 80 and over ; Arthroplasty, Replacement ; methods ; Connective Tissue ; surgery ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Postoperative Complications ; prevention & control ; Shoulder Fractures ; surgery ; Shoulder Joint ; surgery

OBJECTIVEDiscussing the natural history and the influencing factors of HIV infection among former commercial blood and plasma donors engaged in unsafe blood donation practices in China.

METHODSUsing ambispective cohort study, with data obtained from ten counties (districts) from six provinces in the National AIDS Control Demonstration Area. HIV/AIDS cases were found and confirmed prior to July 24, 2006 being former commercial blood. Plasma donors were selected and data regarding infection, incidence, death, and influencing factors was collected. Analysis was performed using SPSS 12.0 statistical analysis software.

RESULTS(1) In 7551 cases of HIV infection, there were 6533 typical progressors (86.52%, 4757 cases of AIDS), 108 rapid progressors (1.43%), 910 long-term non-progressors (12.05%) with 4865 cases progressed to AIDS (64.43%). The median incubation period for HIV progression to AIDS was nine years (95% CI:8.96-9.04). (2) According to data, from a total of 1157 AIDS cases without ARV therapy (23.78% of total AIDS cases), there were 283 confirmed AIDS-related deaths, of which the median survival time was 6 months (95% CI:4-7) and the two and three year fatality rates were 95% and 99%, respectively. (3) The duration of HIV incubation period was irrespective to gender and age at the time of HIV infection (P > 0.05). Length of survival for untreated AIDS showed correlation to gender (P < 0.05) but no correlation with culture, marital status or age at the time of diagnosis of AIDS (P > 0.05).

CONCLUSIONCompared with the UNAIDS theory regarding slow disease progressors among adults, our study showed a longer AIDS incubation period and shorter outlook for untreated survival, but a similar incubation period for other routes of HIV infection.

Acquired Immunodeficiency Syndrome ; epidemiology ; mortality ; Adolescent ; Adult ; Aged ; Blood Donors ; statistics & numerical data ; China ; Female ; HIV Infections ; epidemiology ; mortality ; Humans ; Infectious Disease Incubation Period ; Male ; Middle Aged ; Young Adult

OBJECTIVETo study lateral pelvic metastasis and micrometastasis of low rectal cancer and elucidate their prognostic value.

METHODSWhole-mount slice and tissue microarray of dissected lateral pelvic specimen from 67 cases of low rectal cancer were examined, and the included cases were followed up.

RESULTSTwelve specimens were diagnosed as lateral metastasis, while another 10 were proved to bear micrometastasis. Most of the involved metastatic lymph nodes (82.9%) were smaller than 5 mm in diameter. Internal iliac, obturator regions and middle rectal root were more likely to be involved by tumors. Patients with lateral metastasis suffered more recurrence and poorer survival.

CONCLUSIONSLateral pelvic metastasis could be observed in low rectal cancer and its incidence differed among lateral pelvic regions. Patients with lateral spread predisposed poor prognosis, thus underlies the value of pre/postoperative adjuvant therapy.

Adult ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision ; Lymphatic Metastasis ; Male ; Middle Aged ; Pelvis ; pathology ; Prognosis ; Rectal Neoplasms ; pathology ; surgery