Objective To analyze the role of hDOT1L signaling pathway on the proliferation of human acute monocytic leukemia cell line THP-1 cell inhibited by demcitabine, and to explore the other effects except DNA demethylation and the mechanism of hDOT1L signaling pathways involved in leukemia. Methods Methyl thiazolyl tetrazolium (MTT) method was used to detect the influence of decitabine on THP-1 cell proliferation, and trypan blue anti-staining was applied to detect the effect of decitabine on THP-1 cell survival rate, reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the expression levels of hDOT1L, HOXA9, HOXA10, MLL-AF10 (MLLT10) mRNA, then the methylation level of H3K79 was detected by Western blotting assay. Results Compared with the control group, decitabine inhibited the proliferation of THP-1 cell in a time and dose-dependent manner. The inhibitory effect of 72 h was the highest, and the highest inhibition rate was 56.18%. In addition to 0.5 μmol/L in decitabine treatment group, the other groups were statistically significant (all P<0.05). There were high expressions of hDOT1L, HOXA9, HOXA10, MLLT10 mRNA and H3K79 hypermethylation in the THP-1 cell, meanwhile decitabine reduced the levels of hDOT1L mRNA after 48 h as well as HOXA9, HOXA10, MLLT10 mRNA, and there was a significant difference compared with the control group (all P < 0.01). Decitabine reduced obviously the methylation of H3K79 in cell after 48 h, especially the expression levels of bis and three methyl protein, and these differences were significant compared with the control group (all P< 0.01). Conclusion Decitabine plays its inhibitory effect on the proliferation of THP-1 cells probably through reducing the expression level of hDOT1L and H3K79 methylation level and decreasing the expression levels of key molecules, HOXA9, MLL-AF10, HOXA10, MLLT10 in the hDOT1L signal pathway.

Objective To study the expression of PI3K and Akt mRNA in acute leukemia(AL) and chronic myelocytic leukemia (CML) and try to find out a relationship between the prognostic significance of acute leukemia and the expression level of PI3K and Akt. Methods The samples were collected from 63 ALpatients, 7 relapsed AL patients, 14 CML patients and 10 AL patients in complete remission(CR) patients, 11samples of normal controls(NC). The expression of PI3K, Akt mRNA were measured by semi-quantity reverse transcription polymerase chain reaction(RT-PCR). Results The expression of PI3K mRNA in AL and relapse group were significantly higher than that in normal control. In CML, the P13K mRNA expression level was higher than that in NC and CR. The similar results of the expression of Akt mRNA were observed in CML, NC and CR. At the same time, the expression level of Akt mRNA in relapse group was significantly higher than that in NC. The complete remission rate in PI3K (+) was lower than that in PI3K (-). Similar result was obtained in Akt (+) and Akt (-). Conclusion The PI3K/Akt pathway may contribute to the occurrence of leukemia. The patients with positive expression of the members of this pathway had a lower remission rate.

BACKGROUND:Cytotoxicity of graphene oxide to normal cel s is relatively low, but whether graphene oxide loaded with doxorubicin has some effects on malignant cel s is rarely reported. OBJECTIVE:To explore the cytotoxicity of graphene oxide loaded with doxorubicin on multiple myeloma cel s. METHODS:Multiple myeloma cel line RPMI8226 in logarithmic phase was selected, cultured and divided into four groups, including graphene oxide loaded with doxorubicin, doxorubicin and graphene oxide groups as wel as control group with no intervention. After 24 hours of culture, the cel activity was detected by cel counting kit-8 method, and the cel cycle and apoptosis were detected using flow cytometry. RESULTS AND CONCLUSION:Plump-shaped cel s with translucent and clear cytoplasm were found in the control group;cel s with relatively translucent cytoplasm, and even a few shrunken cel s appeared in the graphene oxide group;cel ular morphology was in a heterogeneity, apoptotic bodies appeared in the doxorubicin group;the cel s was significantly reduced in size, presenting more obvious shrinkage and apoptotic bodies in the group of graphene oxide loaded with doxorubicin. The cel survival rate in the graphene oxide loaded with doxorubicin, doxorubicin and graphene oxide groups was significantly lower than that in the control group (P<0.05), and this indicator was significantly lower in the group of graphene oxide loaded with doxorubicin than the graphene oxide group (P<0.05). The apoptotic rate in the group of graphene oxide loaded with doxorubicin and doxorubicin group was significantly higher than those in the graphene oxide and control groups (P<0.05), respectively. Additional y, there were no significant differences in the cel cycle among groups. These results show that graphene oxide loaded with doxorubicin has a stronger cytotoxicity, and can induce apoptosis in human multiple myeloma cel s.

Objective To investigate the expression of suppressor of cytokine signaling genes (SOCSs) and JAKs mRNA in the acute myloid leukemia(AML) patients. Methods The expression of SOCSs and JAKs mRNA as well as TYK2 in AML patients and healthy adults as normal contrals (NC) was measured with RT-PCR. Results The expression of SOCS 1,4,5 and 7 in AML patients was lower than those in normal control and AML with remis-sion (P<0.01),but the expression of SOCS 3 and 6 was higher than those in normal control and remission AML(P<0.01),however there was no significant difference in SOC2 between groups. The expressions of JAK2 ,JAK3 and TYK2 in AML were significantly higher than those in patients with remission and normal control(P<0.05). The ex-pression of JAK1 mRNA in relapsed AML was higher than that in normal control group(P<0.05),but the latter has no statistical significance between beginning treatment and normal group(P>0.05). Conclusion The deletion and degradion of SOCS 1,4,5 and 7 present in AML patients and JAKs expression is significantly increased, suggesting that both of them may co-participate in the pathogenesis of AML.

Objective To study the in vitro cytotoxicity of HRZ (isoniazid + rifampin + pyrazinamide) / transforming growth factor (TGF) β1 siRNA nanoliposomes on human macrophages and the underlying mechanism. Methods Self-made nanoliposomes were used to study with the cultured human macrophages in vitro. MTT assay was used to detect cell proliferation. Flow cytometry was used to analyze apoptosis and cell cycle. Electron microscopy was used to observe autophagy. RT-PCR and Western blot were employed to analyze the silenced expression of target gene TGF-β1. Results HRZ/TGF-β1 siRNA nanoliposomes (triple liposome) inhibited macrophage proliferation within certain range of concentration, and cell cycle was captured in G2 phase. The HRZ / TGF-β1 SiRNA nanoliposomes could significantly inhibit the expression of target gene TGF-β1 in human macrophages. Conclusions The self-made triple liposome has evident effect in silencing the target gene. It is a promising biomaterial, which meets the required specifications in terms of cytotoxicity.

Objective:To investigate the prevalence, risk factors and outcomes of diastasis recti abdominis (DRA) in multiparas after the second delivery.Methods:From June 2017 to September 2019, 300 multiparas with an average age of (31.7±4.0) years (26 to 43 years) after the second delivery were recruited at 6 weeks postpartum from two hospitals in Wenzhou. There were 171 multiparas with two natural births,36 multiparas with one natural birth and one caesarean delivery, and 93 multiparas with two caesarean deliveries. The interrectus distance (IRD) was measured with palpation at 6 weeks, 6 months and 12 months after delivery. Data on age, height, weight before pregnancy and delivery, baby′s birth weight, abdominal circumference before pregnancy and delivery, fetus number, delivery mode and occupation type were collected. Strength and endurance of abdominal muscle was assessed using manual muscle testing and curl-ups, low back pain was assessed using Oswestry disability index(ODI), urinary incontinence was assessed with International Consultation on Incontinence guestionnaire-incontinentia urinae (ICIQ-UI) short form (ICIQ-SF), and quality of life was assessed using 36-item short form health survey (SF-36).Results:Prevalence of DRA was 51.7%(155/300), 39.3%(116/295) and 27.7%(80/289) 6 weeks, 6 months and 12 months after delivery, respectively. Logistic regression analysis indicated that age ( OR=1.39, 95 %CI:1.02-1.91, P=0.38), abdominal circumference ratio ( OR=2.31, 95 %CI:1.23-4.33, P=0.01), twins ( OR=11.41, 95 %CI:2.15-60.76, P<0.01), and cesarean section ( OR=1.44, 95 %CI:1.06-1.95, P=0.02) were the risk factors of DRA at 12 months after delivery. At 12 months after delivery, the multiparas with DRA had weaker strength and endurance of abdominal muscle ( Z=-3.62, P<0.01; Z=-8.91, P<0.01), more serious low back pain ( Z=-2.10, P=0.04), and lower quality of life on physical health ( t=-3.34, P<0.01) than the multiparas without DRA. No difference in prevalence and severity of urinary incontinence and quality of life on psychological health was found when comparing multiparas with and without DRA (χ 2=0.66, P=0.42; Z=-1.18, P=0.24; t=0.91, P=0.36). Conclusion:Multipara after the second delivery has great likelihood for DRA.Age, abdominal circumference ratio, twins, and cesarean section are the risk factors of DRA. DRA is related to abdominal muscle dysfunction, low back pain, and quality of life.

PEP06 is a novel endostatin-Arg-Gly-Asp-Arg-Gly-Asp(RGDRGD)30-amino-acid polypeptide featuring a terminally fused RGDRGD hexapeptide at the N terminus.The active endostatin fragment of PEPO6 directly targets tumor cells and exerts an antitumoral effect.However,little is known about the kinetics and degradation products of PEP06 in vitro or in vivo.In this study,we investigated the in vitro metabolic stability of PEP06 after it was incubated with living cells obtained from animals of different species;we further identified the degradation characteristics of its cleavage products.PEP06 underwent rapid enzymatic degradation in multiple types of living cells,and the liver,kidney,and blood play important roles in the metabolism and clearance of the peptides resulting from the molecular degradation of PEP06.We identified metabolites of PEP06 using full-scan mass spectrometry(MS)and tandem MS(MS2),wherein 43 metabolites were characterized and identified as the degradation metabolites from the parent peptide,formed by successive losses of amino acids.The metabolites were C and N terminal truncated products of PEP06.The structures of 11 metabolites(M6,M7,M16,M17,M21,M25,M33,M34,M39,M40,and M42)were further confirmed by comparing the retention times of similar full MS spectrum and MS2 spectrum information with reference standards for the synthesized metabolites.We have demonstrated the metabolic stability of PEP06 in vitro and identified a series of potentially bioactive downstream metabolites of PEP06,which can support further drug research.

OBJECTIVE: To investigate the short-term effectiveness of transverse antecubital incision in the treatment of failed closed reduction of Gartland type Ⅲ supracondylar humeral fractures (SHFs) in children. METHODS: Between July 2020 and April 2022, 20 children with Gartland type Ⅲ SHFs who failed in closed reduction were treated with internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision. There were 9 boys and 11 girls with an average age of 3.1 years (range, 1.1-6.0 years). The causes of injuries were fall in 12 cases and fall from height in 8 cases. The time from admission to operation ranged from 7 to 18 hours, with an average of 12.4 hours. The healing of the incision and the occurrence of complications such as nerve injury and cubitus varus were observed after operation; the elbow flexion and extension range of motion after removing the gypsum, after removing the Kirschner wire, and at last follow-up were recorded and compared, as well as the elbow flexion and extension and forearm rotation range of motion at last follow-up between healthy and affected sides; the Baumann angle was measured on the X-ray film, and the fracture healing was observed. At last follow-up, the effectiveness was evaluated according to the Flynn elbow function evaluation criteria. RESULTS: All incisions healed by first intention, and there was no skin necrosis, scar contracture, ulnar nerve injury, and cubitus varus. Postoperative pain occurred in the radial-dorsal thumb in 2 cases. The gypsum was removed and elbow flexion and extension exercises were started at 2-4 weeks (mean, 2.7 weeks) after operation, and the Kirschner wire was removed at 4-5 weeks (mean, 4.3 weeks). All the 20 patients were followed up 6-16 months, with an average of 12.4 months. The fracture healing time was 4-5 weeks, with an average of 4.5 weeks, and there was no complication such as delayed healing and myositis ossificans. The flexion and extension range of motion of the elbow joint gradually improved after operation, and there were significant differences between the time after removing the gypsum, after removing the Kirschner wire, and at last follow-up ( P<0.017). There was no significant difference in the flexion and extension of the elbow joint and the forearm rotation range of motion between the healthy and affected sides at last follow-up ( P>0.05). There was no significant difference in Baumann angle between the time of immediate after operation, after removing the Kirschner wire, and at last follow-up ( P>0.05). According to Flynn elbow function evaluation standard, 16 cases were excellent and 4 cases were good, the excellent and good rate was 100%. CONCLUSION The treatment of Gartland type Ⅲ SHFs in children with failed closed reduction by internal and external condylar crossing Kirschner wire fixation through transverse antecubital incision has the advantages of complete soft tissue hinge behind the fracture for easy reduction and wire fixation, small incision, less complications, fast fracture healing, early functional recovery, reliable reduction and fixation, and can obtain satisfactory results.
Male ; Female ; Humans ; Child ; Child, Preschool ; Calcium Sulfate ; Humerus ; Humeral Fractures/surgery* ; Plastic Surgery Procedures ; Fracture Fixation, Internal/methods* ; Bone Wires ; Fracture Healing ; Treatment Outcome ; Range of Motion, Articular

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.
Humans ; Pulse Wave Analysis ; Albuminuria ; Ankle Brachial Index ; Non-alcoholic Fatty Liver Disease/diagnosis* ; Vascular Stiffness ; Prospective Studies ; Risk Factors ; China/epidemiology*