How does economic inequality shape conspiracy theories? Empirical evidence from China.

Conspiracy theories tend to be prevalent, particularly in societies with high economic inequality. However, few studies have examined the relationship between economic inequality and belief in conspiracy theories. We propose that economic inequality leads people to believe conspiracy theories about economically advantaged groups (i.e., upwards conspiracy theories) and that moral evaluations of those groups mediate this relationship. Study 1 (N = 300) found support for these ideas in a survey among Chinese residents. Study 2 (N = 160) manipulated participants' perceptions of economic inequality in a virtual society. The manipulation shaped moral evaluations of economically advantaged groups, and conspiracy beliefs, in the predicted manner. In Study 3 (N = 191) and Study 4 (N = 210), we experimentally manipulated participants' perceptions of economic inequality in real Chinese society and replicated the results of Study 2. In addition, in Study 4, we find that economic inequality predicts belief in conspiracy theories about economically disadvantaged groups (i.e., downward conspiracy theories), which was mediated by anomie. We conclude that perceived economic inequality predicts conspiracy theories about economically advantaged groups and that moral evaluations account for this effect. Also, upward and downward conspiracy theory beliefs are associated with different psychological processes.

Guideline for the diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients (version 2023) / 中华创伤杂志

Chronic refractory wound (CRW) is one of the most challengeable issues in clinic due to complex pathogenesis, long course of disease and poor prognosis. Experts need to conduct systematic summary for the diagnosis and treatment of CRW due to complex pathogenesis and poor prognosis, and standard guidelines for the diagnosis and treatment of CRW should be created. The Guideline forthe diagnosis and treatment of chronic refractory wounds in orthopedic trauma patients ( version 2023) was created by the expert group organized by the Chinese Association of Orthopedic Surgeons, Chinese Orthopedic Association, Chinese Society of Traumatology, and Trauma Orthopedics and Multiple Traumatology Group of Emergency Resuscitation Committee of Chinese Medical Doctor Association after the clinical problems were chosen based on demand-driven principles and principles of evidence-based medicine. The guideline systematically elaborated CRW from aspects of the epidemiology, diagnosis, treatment, postoperative management, complication prevention and comorbidity management, and rehabilitation and health education, and 9 recommendations were finally proposed to provide a reliable clinical reference for the diagnosis and treatment of CRW.

An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023) / 中华创伤杂志

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Stroke risk evaluation for patients with atrial fibrillation: Insights from left atrial appendage with fluid-structure interaction analysis.

The majority of cardioembolic strokes in patients with non-valvular atrial fibrillation (NVAF) are resulted from clot formation in the left atrial appendage (LAA). Current stroke risk stratification is based on the overall risks estimated from demographic and clinical profiles but not on individual anatomy or physiology. We aim to explore the differences in LAA morphological and hemodynamic parameters by comparing patients with and without a stroke history. Thirty-nine patients with persistent NVAF were included. Of these, 17 patients without a stroke history (non-stroke group) were compared with 22 patients with a history of stroke (stroke group). Their LAA geometric models were first reconstructed, and the morphological parameters were then measured. Furthermore, their LAA hemodynamic parameters were calculated by fluid-structure interaction analysis. Moreover, particle residual rates (PRR) and blood renewal rates (BRR) analyses were also employed to characterize the thrombogenesis dynamics. The results showed that compared to the non-stroke group, the stroke group had significant smaller LAA tortuosity and LAA orifice area, and significantly lower LAA orifice velocities (0.16 ± 0.10 vs 0.15 ± 0.06 cm/s; p = 0.044), but higher PRR (14.58 ± 9.43 vs 9.25 ± 4.67; p = 0.040) and BRR (52.41 ± 18.11 vs 38.36 ± 24.07; p = 0.044). These LAA morphological and hemodynamic parameters may be used to assess stroke risk in patients with NVAF.

Using informational questionnaires to turn blood donors into hematopoietic stem cell voluntary donors: a randomized controlled trial / 中国输血杂志

【Objective】 To explore effective ways to mobilize more blood donors to become voluntary donors of hematopoietic stem cells (HSCs), so as to increase the HSCs supply in China. 【Methods】 Two scales(the information scale and the control scale) with the same items were designed and both included questions concerning the knowledge of HSCs donation and the level of demand. The information scale indicated the correct answer to these questions, while the control scale did not. A total of 3 000 blood donors in Guangzhou were randomly assigned into the intervention group (n=1 500, filled in the information scale) and the control group (n=1 500, filled in the control scale). 【Results】 Blood donors who filled in the informational scale expressed a higher intention to become HSCs volunteers (MInformation =4.32, SD=0.87; MControl=4.02, SD=0.93, t(529)=3.87, P<0.001). Altruism and perceived need (the degree of HSCs demands) were the moderators of grouping and intention, that is, the information scale made blood donors, with stronger altruism and higher perceived need, more willing to become stem cell volunteers. Perceived risk (the negative impact of HSCs donation on health) was a partial mediator of grouping and intention. The information scale reduced blood donors' anxiety about the risk of HSCs donation, and promoted their intention to become HSCs volunteers. 【Conclusion】 This study proved that the informational scale can effectively mobilize blood donors to become HSCs volunteers.

Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C.

Chemotherapy resistance remains to be the primary barrier to acute myeloid leukemia (AML) treatment failure. Nuclear factor-erythroid 2-related factor 2 (Nrf2) has been well established as a truly pleiotropic transcription factor. Inhibition of Nrf2 function increases the sensitivity of various chemotherapeutics and overcomes chemoresistance effectively. Brusatol (Bru) has been reported to decrease Nrf2 protein expression specifically by ubiquitin degradation of Nrf2. However, it remains elusive whether combination of Brusatol and Cytarabine (Ara-C) elicits a synergistic antitumor effect in AML. Our results demonstrated that combination of Ara-C and Brusatol synergistically exerted remarkable pro-apoptosis effect in HL-60 and THP-1 cells. Mechanistically, synergistic anti-tumor effect of Ara-C/Brusatol in AML cells is mediated by attenuating Nrf2 expression. To our surprise, Nrf2 inhibition by Brusatol causes downregulation of the expression of glycolysis-related proteins and decreased glucose consumption and lactate production, whereas the level of ROS production was unaffected. The activation of Nrf2 by Sulforaphane (SFP) could reverse the chemotherapeutic effect and changes of glycolysis of concomitant of Ara-C with Brusatol in AML cell lines. Additionally, Ara-C/Brusatol co-treatment decreased Glucose-6-phosphate dehydrogenase (G6PD) protein expression and increased the sensitivity of Ara-C. Moreover, the mouse xenograft in vivo experiment confirmed that combining Ara-C with Brusatol exerted stronger antileukemia than Ara-C alone. The efficacy, together with the mechanistic observations, reveals the potential of simultaneously giving these two drugs and provides a rational basis for targeting glucose catabolism in future clinical therapeutic approach.

TBC1D16 predicts chemosensitivity and prognosis in adult acute myeloid leukemia (AML) patients.

Acute myeloid leukemia (AML) is a hematopoietic disease with poor survival. Chemotherapy resistance is one of the determinant factors influencing AML prognosis. To identify genes possibly affecting the drug responses in AML, the Illumina Infinium MethylationEPIC (850K) was used to screen for differential DNA methylation loci between patients achieved complete remission (CR) or not (non-CR) after induction therapy in 37 AML patients. Then, 32 differentially methylated sites (DMS) were selected for replication in another 86 AML patients by next-generation sequencing. Nine sites including cg03988660, cg16804603, cg18166936, cg11308319, cg09095403, cg18493214, cg01443536, cg16030878 and cg10143426 were replicated. Analysis of the Gene Expression Omnibus (GEO) database showed that mRNA expression of TBC1D16 and HDAC4 was associated with AML prognosis. Methylation level of the cg16030878 in TBC1D16 3'-UTR correlated positively with TBC1D16 mRNA expression in samples both in the TCGA database and clinically collected in the study. Both higher cg16030878 methylation and higher TBC1D16 mRNA expression were associated with increased risk of non-CR and worse overall survival (OS) in AML patients. In AML cells, knockdown of TBC1D16 decreased cell proliferation and ERK phosphorylation levels, as well as increased sensitivity to mitoxantrone and decitabine indicated by IC50. In patients with combined use of decitabine, those patients with CR showed significantly lower TBC1D16 mRNA expression. On the contrary, knockdown of TBC1D16 resulted in decreased sensitivity to cytarabine in U937 cells. Our findings implicated that TBC1D16 is a potential predictor for chemosensitivity and prognosis in adult AML patients.

Debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images / 中华创伤杂志

Objective:To explore the debridement effectiveness of infected bone tissue of chronic hematogenous osteomyelitis in the lower extremities under the guidance of 99mTc-MDP SPECT/CT fused images. Methods:A retrospective case series analysis was conducted on 21 patients with chronic hematogenous osteomyelitis in the lower extremities treated at Southwest Hospital of Army Medical University from May 2017 to June 2020. There were 8 males and 13 females, with the age range of 10-62 years [23(18, 37)years]. The tibial infections were found in 16 patients, and femoral infections in 5 patients. The duration of bone infection was 4-480 months [120(42, 228)months]. According to the Cierny-Mader anatomico-physiological system, 4 patients were classified as type I, 14 as type III, 3 as type IV; 18 patients were classified as type A and 3 as type B. Intraoperative debridement of infected bone tissue was operated at stage I on the region of interest (ROI) where the isocontour(ISO) value was between 30%-40%, using the preoperative 99mTc-MDP SPECT/CT fused images as the reference. The stage II bone defect reconstruction was based on autologous and / or allogeneic bone. To observe the frequency of operations regarding bone infection control in stage I. The preoperative white blood cell count (WBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), intraoperative bacterial culture and pathological examination were compared at stages I and II. The skin redness and swellings, pain, sinus tract in the infected limbs, and ossification of grafted bones in the original bone defect part were observed at stage II. The accuracy rate between ISO value in the region of interest (ROI) and set ISO figure was checked. The difference of longitudinal length of the bone debridement area in ROI area with the actual bone debridement area was observed under the coronal position. Results:All patients were followed up for 6-36 months [11(9, 29)months] after stage II operation. All of the 21 patients had undergone operations of infection control with an average number of 1.04 times in stage I. 1 patient's intraoperative frozen section indicated that neutrophils were>5/HP. The bone graft at stage II had been completed after another debridement. Comparison of preoperative inflammatory markers at stages I and II: the WBC was decreased from (5.9±1.6)×10 9/L to (5.4±1.5)×10 9/L ( P>0.05), the ESR decreased from 9(5, 26)mm/h to 4(2, 10)mm/h ( P<0.05), and the CRP decreased from 2.8(2.3, 7.7)mg/L to 2.3(1.4, 3.0)mg/L ( P>0.05). The results of bacterial culture of tissue at stage I were positive in 12 patients and negative in 9 patients. The pathological examination indicated neutrophils and lymphocyte infiltration. The results of bacterial culture of tissue at stage II were all negative. A modicum of plasmacyte and lymphocyte infiltration and the neutrophils (<5 per/Hp) had been found in the intraoperative frozen section and pathological examination. No redness, swelling or sinus tract was found in the skin after stage II surgery and ossification of grafted bone was good. The accuracy rate between ISO value in the ROI and set ISO figure was 90.5%. The comparison between longitudinal debridement scope of ROI [(86.8±31.1)mm] and actual bone tissue debridement scope [(86.0±31.3)mm] at stage I showed no significant difference ( P>0.05). Conclusions:99mTc-MDP SPECT/CT fused images can be used as an effective means to define the debridement scope of infected bone tissue preoperatively. The method can not only avoid excessive debridement, but also improve the cure rate of hematogenous osteomyelitis in the lower extremities.

L-Arginine Supplementation Improves Vascular Endothelial Dysfunction Induced by High-Fat Diet in Rats Exposed to Hypoxia.

INTRODUCTION: Our previous study showed that high-fat diet inhibited the increase in nitric oxide and endothelial nitric oxide synthase expression in the aortic endothelium of rats exposed to hypoxia, and hypoxia plus a high-fat diet led to earlier and more severe vascular endothelial dysfunction (VED) than hypoxia alone. The purpose of the present study was to investigate the effects of L-arginine on high-fat diet-induced VED of rats in hypoxia. METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups and treated with hypoxia (H group), hypoxia plus high-fat diet (H+HFD group), hypoxia plus L-arginine (H+L-Arg group), and hypoxia plus high-fat diet and L-arginine (H+HFD+L-Arg group) for 1 wk. Hypoxia was simulated in a hypobaric chamber with an altitude of 5000 m. Aortic morphology and endothelium-dependent vasorelaxation were used to assess VED. RESULTS: High-fat diet impaired vascular remodeling and reduced endothelium-dependent vasodilator response to acetylcholine in rats exposed to hypoxia, secondary to dysregulation of the nitric oxide pathway. L-arginine supplementation significantly increased plasma nitrates and nitrites and endothelial nitric oxide synthase mRNA levels and improved ultrastructural changes in aortic endothelium and endothelium-dependent vasodilator response. CONCLUSIONS: L-arginine prevents aortic ultrastructural changes and reverses VED induced by high-fat diet in rats exposed to hypoxia, which may have implications for VED induced by high-fat diet in high altitude dwellers.

Chidamide acts on the histone deacetylase-mediated miR-34a/Bcl-2 axis to regulate NB4 cell line proliferation and apoptosis.

Acute promyelocytic leukemia (APL), a biologically and clinically distinct variant of acute myelogenous leukemia, is characterized by the fusion of the N-terminus of promyelocytic leukemia protein to the C terminus of retinoic acid receptor alpha, mostly due to chromosomal translocation t(15;17). Chidamide, a synthetic analogue of MS-275 identified from a group of benzamide-type compounds, has been found to have efficient anticancer activity in basic and clinical research studies. However, the concrete role and underlying mechanism of Chidamide in the treatment of APL has not been well characterized. Our data demonstrate that Chidamide inhibited the expression of histone deacetylase (HDAC) to induce apoptosis and suppress proliferation in NB4 cells. Mechanistically, Chidamide increases the expression of miR-34a by suppressing HDAC. Furthermore, B-cell lymphoma-2 (Bcl-2) is a direct target of miR-34a, the expression of which is regulated by miR-34a. Functionally, Chidamide inhibits cell proliferation and promotes apoptosis through miR-34a/Bcl-2. Chidamide exerts its anticancer effect via the HDAC-mediated miR-34a/Bcl-2 axis, providing potential targets for APL therapy.

Roles of hsa-miR-12462 and SLC9A1 in acute myeloid leukemia.

MicroRNAs (miRNAs) play important roles in cell proliferation, differentiation, and survival and may be useful for acute myeloid leukemia (AML) diagnosis and prognosis. In this study, we defined a novel miRNA, hsa-miR-12462, through small RNA sequencing of the bone marrow (BM) cells from 128 AML patients. Overexpression of hsa-miR-12462 in AML cells (U937 and HL-60) significantly decreased their growth rate when compared with those of the wild-type and MOCK controls. In a xenograft mouse model, tumor weight and size in the mice bearing the U937 cells with hsa-miR-12462 overexpression were significantly reduced when compared with those bearing the mock cells. The AML cells overexpressing hsa-miR-12462 had increased sensitivity to cytarabine chemotherapy. Combining the data from the MiRDB, an online microRNA database ( http://mirdb.org ), with the RNA-sequencing results, SLC9A1 was predicted to be one of the targets of hsa-miR-12462. hsa-miR-12462 was further confirmed to bind exclusively to the 3'UTR of SLC9A1 in U937 cells, leading to downregulation of SLC9A1. In summary, a higher level of hsa-miR-12462 in AML cells is associated with increased sensitivity to cytarabine chemotherapy via downregulation of SLC9A1.

Down-regulating NQO1 promotes cellular proliferation in K562 cells via elevating DNA synthesis.

BACKGROUND: NQO1 protein acts as a cellular protective system, on account of its role as a quinone reductase and redox regulator. Nonetheless, new NQO1 roles are emerging-including its regulation of the cellular proliferation of many tumor cells-and this enzyme has been found to relate to the incidence of various diseases, including chronic myeloid leukemia. However, the mechanisms through which NQO1 influences leukemia progression remain unclear. MARTIAL AND METHODS: The current study looks to name NQO1 as a novel molecular target that modulates DNA synthesis and chronic myeloid leukemia growth. RESULTS AND CONCLUSION: Our results indicate that the frequency of the T allele of NQO1 polymorphism in chronic myeloid leukemia patients is higher than that among healthy East Asian individuals (0.492 vs. 0.419) and much higher than the average level of the general population (0.492 vs. 0.289) (1000 Genomes). Functionally, NQO1 knockdown increases the protein expression of the TOP2A and MCM complex, and consequently promotes DNA synthesis and K562 cell growth. NQO1 knockdown also promotes tumorigenesis in a xenograft model. NQO1 overexpression, on the other hand, was found to have the opposite effects. SIGNIFICANCE: Our results show that NQO1 downregulation promotes K562 cellular proliferation via the elevation of DNA synthesis.

Effects of Trough Concentration and Solute Carrier Polymorphisms on Imatinib Efficacy in Chinese Patients with Chronic Myeloid Leukemia.

PURPOSE: We investigated the relationship between imatinib trough concentrations and genetic polymorphisms with efficacy of imatinib in Chinese patients with chronic myeloid leukemia (CML). METHODS: There were 171 eligible patients. Peripheral blood samples were collected from 171 eligible patients between 21 and 27 hours after the last imatinib administration. Complete cytogenetic response (CCyR), major molecular response (MMR) and complete molecular response (CMR) were used as metrics for efficacy. Nine single nucleotide polymorphisms in 5 genes, SLC22A4 (917 T>C, -248 C>G and -538 C>G), SLC22A5 (-945 T>G and -1889 T>C), SLCO1A2 (-361 G>A), SLCO1B3 (334 T>G and 699 G>A) and ABCG2 (421C>A) were selected for genotyping. RESULTS: Patients with CCyR achieve higher trough concentrations than those without CCyR (1478.18±659.83 vs 984.89±454.06 ng mL-1, p<0.001). Patients with MMR and CMR achieve higher trough concentrations than those without MMR and CMR, respectively (1486.40±703.38 vs 1121.17±527.14 ng mL-1, p=0.007; 1528.00±709.98 vs 1112.67±518.35 ng mL-1, p=0.003, respectively). Carriers of A allele in SLCO1A2 -361G>A achieve higher CCyR and MMR rates (p=0.047, OR=4.320, 95% CI: 0.924-20.206; p=0.042, OR=2.825, 95% CI: 1.016-7.853, respectively). Both trough concentrations and SLCO1A2 -361G>A genotypes are independent factors affecting imatinib efficacy. The positive and negative predictive values for CCyR are 71.01% and 68.75%, respectively. The positive and negative predictive values for MMR are 62.86% and 69.70%, respectively. CONCLUSION: Imatinib trough concentrations and SLCO1A2 -361G>A genotypes are associated with imatinib efficacy in Chinese patients with CML.

CDK6 Is a Potential Prognostic Biomarker in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a threatening hematological malignant disease in which new successful approaches in therapy are needed. Cyclin-dependent kinase 6 (CDK6), a regulatory enzyme of the cell cycle that plays an important role in leukemogenesis and the maintenance of leukemia stem cells (LSC), has the potential to predict the prognosis of AML. By analyzing public databases, we observed that the messenger RNA (mRNA) levels of CDK6 were significantly overexpressed in AML cell lines and non-acute promyelocytic leukemia (non-APL) AML patients when compared to healthy donors. Furthermore, CDK6 expression was significantly reduced in AML patients who achieved complete remission (CR) compared to that at the time of diagnosis in our validated cohort. The expression of CDK6 was tightly correlated with peripheral blood blasts, French-American-British (FAB) subtypes, CCAAT-enhancer-binding protein α (CEBPA) mutation, and chromosomal abnormalities of t(8;21). However, the clinical significance and effects of CDK6 expression on the prognosis of non-APL AML patients remain uncertain. We found that CDK6 expression was inversely correlated with overall survival (OS) among non-APL AML patients using the Kaplan-Meier analysis. CDK6 was also found to be positively associated with genes identified to contribute to the development of leukemia, including CCND2, DNMT3B, SOX4, and IKZF2, as well as being negatively associated with anticancer microRNAs, including miR-187, miR-9, miR-582, miR708, and miR-362. In summary, our study revealed that CDK6 might be a potential diagnostic and prognostic biomarker in non-APL AML patients.

Titanium cable binding plate combined with proximal femoral nail antirotation for recurrent fractures after treatment of unstable intertrochanteric fractures / 中华创伤杂志

Objective:To investigate the clinical effect of titanium cable binding plate combined with lengthened proximal femoral nail antirotation (PFNA) for fixation of recurrent fracture after treatment of unstable intertrochanteric fractures.Methods:A retrospective case series study was conducted for analyzing the clinical data of 17 patients with recurrent fracture of unstable intertrochanteric fractures admitted to Southwest Hospital of Army Medical University from January 2010 to January 2018. There were 7 males and 10 females, aged from 65 to 94 years [(75.7±13.2)years]. The patients were treated using titanium cable binding plate combined with PFNA. Anti-osteoporosis therapy was applied as well. X-ray images were performed at postoperative 3 days, 3, 6 and 12 months. The healing and complications of the patients were recorded. The Harris hip score, visual analogue score (VAS), physical health score (PCS), mental health score (MCS) and 36-item short form health survey questionnaire (SF-36) were evaluated before operation and at postoperative 6 and 12 months.Results:All patients were followed up for 12-18 months [(15.3±2.8)months]. Bone healing was achieved in all patients, and the postoperative bone healing time was 3-6 months [(3.6±1.1)months]. One patient developed lumbosacral pressure sores and recovered after dressing change. Two patients developed drooping pneumonia, which was completely relieved after symptomatic treatment including nebulized inhalation of antibiotics and sputum aspiration. At postoperative 6 and 12 months, Harris hip score was (76.5±5.2)points and (85.5±5.7)points, significantly higher than (32.8±5.1)points before operation ( P<0.05); VAS was (3.3±0.5)points and (1.2±0.7)points, significantly lower than (8.5±0.7)points before operation ( P<0.05); PCS was (44.2±4.9)points and (56.9±5.8)points, significantly higher than (29.3±4.7)points before operation ( P<0.05); MCS was (47.9±6.8)points and (58.4±7.9)points, significantly higher than (39.7±5.9) points before operation ( P<0.05); SF-36 was (493.9±85.7)points and (603.4±76.8)points, significantly higher than (415.9±88.2)points before operation ( P<0.05). Conclusions:Titanium cable binding plate combined with lengthening PFNA can provide stability of fracture end, promote fracture healing, reduce complications, relieve pain and improve patients' quality of life for recurrence of unstable intertrochanteric fracture.

Clinical efficacy of membrane induction technique for postoperative infection of tibial plateau fracture in adults / 中华创伤杂志

Objective:To investigate the clinical efficacy of membrane induction technique in the treatment of postoperative infection of tibial plateau fractures in adults.Methods:A retrospective case series study was conducted to analyze the clinical data of 21 adult patients with postoperative infection of tibial plateau fractures treated with membrane induction technique from April 2013 to May 2017 in Southwest Hospital of Army Medical University. There were 19 males and two females, aged 19-60 years [(44.1±5.8)years]. There was one patient with type IV fractures, 14 with type V, and 6 with type VI according to the initial fracture typing by Schatzker's classification. There were three patients with infection period of within 3 weeks, 12 of 3-10 weeks, and 6 of over 10 weeks. All patients underwent two-stage operation using membrane induction technique to place cement in the bone defect area. After removal of internal fixation and thorough debridement, antibiotic cement and internal fixation plate were placed at stage I. Bone graft and reconstruction was performed at stage II. The infection indicators were recorded. Infection indices were monitored, including white blood cell count (WBC), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Clearance of infection, bony union and complications were evaluated. Range of motion (ROM) and scoring of Hospital for Special Surgery (HSS) were used to evaluate the function of knee joint.Results:All patients were followed up for 12-62 months with an average of 23.5 months. Compared with 3 months after stage II, the indicators of infection at stage I showed that WBC was decreased from (10.6±2.3)×10 9/L to (6.7±3.5)×10 9/L, ESR decreased from (26.0±5.3)mm/h to (12.1±4.3)mm/h, and CRP decreased from (10.0±1.5)mg/L to (5.8±1.0)mg/L ( P<0.05). Infection was cleared in 17 patients after stage I operation, and the other 4 patients had infection recurrence, which were given stage I debridement again to control the infection. Two patients were treated with local flap transfer to cover the wound because of skin soft tissue defect after debridement. Another two patients underwent knee arthrodesis, and none was amputated. X-ray film indicated bony union in 21 patients at 46 months (mean, 4.5 months) after operation, and clinical bone healing was acquired in all 21 patients. One patient showed donor site infection. No nonunion, recurrence of infection after stage II, deep vein thrombosis or pulmonary embolism occured after the second stage. At the latest follow-up, ROM in patients with infection periods within 3 weeks and 3-10 weeks was singnificantly improved from [(95.2±10.4)° and (85.7±11.5)°] to [(120.2±10.5)° and (98.6±12.2)°] ( P<0.01), but not in patients with infection periods of over 10 weeks ( P>0.05). The HSS score in all patients was significantly improved after operation [(65.6±8.2)points vs. (82.0±6.6)points]( P<0.01). Conclusion:For adult patients with tibial plateau fracture, membrane induction technique can effectively control the postoperative infection, achieve clinical bone healing and improve the knee function.

Design, screening and biological evaluation of novel fatty acid chain-modified oxyntomodulin-based derivatives with prolonged glucose-lowering ability and potent anti-obesity effects.

Recently, oxyntomodulin (OXM) has emerged as a treatment option for type 2 diabetes mellitus and obesity. In order to develop more promising novel OXM derivatives combining glycemic effects of glucagon-like peptide-1 (GLP-1) and lipolytic properties of glucagon, six 12-mer GLP-1 receptor agonists (PP01-PP06) were screened using a phage display method and then fused to OXM (3-37) to generate hybrid OXM derivatives (PP07-PP12). PP11, as a selected starting point, was further site-specifically modified with three lengths of fatty acid chains to provide long-acting conjugates PP13-PP24, among which PP18 was found not only to retain almost the entire balanced activation potency of PP11 in GLP-1/glucagon receptors but also to enhance plasma stability and prolong hypoglycemic activity. PP18 was further confirmed as an insulin secretagogue and glycemic agent in gene knockout mice. The protracted antidiabetic effects and in vivo half-life of PP18 were further proved by hypoglycemic efficacies in diet-induced obesity (DIO) mice and pharmacokinetics tests in Sprague Dawley (SD) rats, respectively. Nevertheless, administration of PP18 once per day normalized food intake, body weight, blood biochemical indexes, insulin resistance and islet function of DIO mice. These preclinical results suggested that PP18, as a novel OXM-based dual GLP-1 and glucagon receptor agonist, may serve as a novel therapeutic approach to treat T2DM and obesity.

Influence of DNMT3A R882 mutations on AML prognosis determined by the allele ratio in Chinese patients.

BACKGROUND: The influence of DNMT3A R882 mutations on adult acute myeloid leukemia (AML) prognosis is still controversial presently. The influence of R882 allele ratio on drug response and prognosis of AML is unknown yet. Besides, it is obscure whether anthracyclines are involved in chemoresistance resulted from R882 mutations. METHODS: DNMT3A R882 mutations in 870 adult AML patients receiving standard induction therapy were detected by pyrosequencing. Associations of the mutants with responses to induction therapy and disease prognosis were analyzed. RESULTS: DNMT3A R882 mutations were detected in 74 (8.51%) patients and allele ratio of the mutations ranged from 6 to 50% in the cohort. After the first and second courses of induction therapy including aclarubicin, complete remission rates were significantly lower in carriers of the DNMT3A R882 mutants as compared with R882 wildtype patients (P = 0.022 and P = 0.038, respectively). Compared with R882 wild-type patients, those with the R882 mutations showed significantly shorter overall survival (OS) and disease-free survival (DFS) (P = 1.92 × 10-4 and P = 0.004, respectively). Patients with higher allele ratio of R882 mutations showed a significantly shorter OS as compared with the lower allele ratio group (P = 0.035). CONCLUSION: Our results indicate that the impact of DNMT3A R882 mutations on AML prognosis was determined by the mutant-allele ratio and higher allele ratio could predict a worse prognosis, which might improve AML risk stratification. In addition, DNMT3A R882 mutations were associated with an inferior response to induction therapy with aclarubicin in Chinese AML patients.

Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia.

AIM: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib. METHODS: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model. RESULTS: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: Ka (1/h) = 0.329; CL/F (l/h) = 9.25 × (actual bodyweight/70)0.228; V/F(l) = 222. CONCLUSION: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.