Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

The novel HLA-B*51:381 allele, identified in a Chinese individual through Sanger dideoxy nucleotide sequencing.

HLA-B*51:381 differs from HLA-B*51:01:01:01 by one nucleotide in exon 5.

Effects of Empagliflozin on Gut Microbiota in Heart Failure with a Preserved Ejection Fraction: The Design of a Pragmatic Randomized, Open-Label Controlled Trial (EMPAGUM).

Although empagliflozin has been recommended for individuals with heart failure, its effects on heart failure with preserved ejection fraction (HFpEF) remain uncertain from a physiopathological standpoint. The metabolites produced by gut microbiota have been shown to have a crucial role in the development of heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2) have been shown to change the make-up of the gut microbiota in rodent studies. There is mixed evidence from similar studies investigating whether or not SGLT2 can affect the microbiota in the human gut. This trial is a pragmatic, randomized, open-label controlled study with empagliflozin as an intervention. We will enroll 100 patients with HFpEF and randomly assign them to one of two groups to receive either empagliflozin or a placebo. Patients in the Empagliflozin group will be given 10 mg of the drug daily, while those in the Control group will not be given empagliflozin or any other SGLT2. The purpose of the trial is to validate the changes that occur in gut microbiota in patients with HFpEF who take empagliflozin and to investigate the function of gut microbiota and their metabolites in the process.

Heteroprotein complex between soy protein isolate and lysozyme: Protein conformation, lysozyme activity, and structural characterization.

Heteroprotein complexes are formed by electrostatic interactions of oppositely charged proteins in a purely aqueous environment. Understanding the relationship between their structural and functional properties will contribute to their tailor-made applications. Therefore, this study investigated the protein conformation, assembling structure, and enzyme activity of soy protein isolate/lysozyme (SPI/LYS) complexes at mass ratios of 2:1 (soluble complex) and 1:1.3 (stoichiometric ratio). Electrostatic complexation increased the surface hydrophobicity of complexes. Their surface hydrophobicity decreased with increasing NaCl concentrations and reached the theoretical values at the critical salt concentration of 200 mM NaCl. Electrostatic complexation did not decrease the LYS activity (∼43,000 units/mg). SPI/LYS complexes exhibited flocculated structures in which the two proteins were unevenly distributed; these were typical amorphous complexes. High dilution disassembled these complexes over 5 µm into particles of ∼100 nm, and NaCl reduced the size of these particles. Immobilized water was detected in the complexes formed by particle flocculation.

Morphological and functional changes in the macular area in diabetic macular edema after a single intravitreal injection of aflibercept.

AIM: To evaluate the changes in macular morphology and function after a single intravitreal injection of aflibercept in diabetic macular edema (DME) using optical coherence tomography angiography (OCTA) and MP-3 microperimetry. METHODS: Twenty-eight patients (42 eyes) diagnosed with DME were treated with intravitreal injection of aflibercept. The changes in best corrected visual acuity (BCVA), central retinal thickness (CRT), foveal avascular zone (FAZ) area, vessel density of superficial retinal capillary plexus (SVD), vessel density of deep retinal capillary plexus (DVD), mean light sensitivity (MLS), 2° fixation rate (P1), 4° fixation rate (P2), and other indicators 1mo after treatment were compared; of these, BCVA was converted into logarithm of the minimum angle of resolution (logMAR), and the correlation among the factors was analyzed. RESULTS: After treatment, logMAR BCVA was 0.47±0.24, which was significantly better than that before treatment (0.63±0.28, P<0.001). The CRT was 359.21±107.87 µm after treatment, which was significantly lower than before treatment (474.10±138.20 µm, P<0.001). The FAZ area, SVD, and DVD were not significantly changed after treatment compared with the baseline. MLS was 22.16±4.20 dB after treatment, which was significantly higher than before treatment (19.63±4.23 dB, P<0.001). P2 significantly increased after treatment than before treatment (P=0.007). P1 had no significant change after treatment than before treatment (P=0.086). CONCLUSION: A single intravitreal injection of aflibercept effectively reduces macular edema and improves retinal sensitivity, fixation stability, and visual acuity, possibly without causing significant changes in the retinal vascular condition in a short time.

Research advances in chest tightness variant asthma / 中华预防医学杂志

Chest tightness variant asthma (CTVA) is a special type of asthma with chest tightness as the only or main symptom. Due to the lack of typical asthma symptoms such as coughing, wheezing, shortness of breath, and positive signs in chest, it is easy to be missed or misdiagnosed in clinical practice. The onset of chest tightness variant asthma is insidious, and there is few research and attention both domestic and international, so there is no unified diagnosis and treatment standard especially in childhood asthma. This article expounds the related research advances in chest tightness variant asthma, in order to increase clinical attention and provide reference and basis for the prevention of the disease as well as the formulation of diagnosis and treatment strategies.

Effectiveness of anterior cruciate ligament reconstruction with personalized femoral locator based on apex of deep cartilage / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effectiveness of anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral locator based on the apex of deep cartilage (ADC) combined with patient imaging data.@*METHODS@#Between January 2021 and January 2022, a total of 40 patients with primary ACL rupture were selected and randomly divided into study group (ACL reconstruction assisted by personalized femoral locator based on ADC) and control group (ACL reconstruction assisted by intraoperative fluoroscopy and traditional femoral locator), with 20 cases in each group. There was no significant difference in gender, age, body mass index, affected side, cause of injury, and preoperative International Knee Documentation Committee (IKDC) score, Lyshlom score, and Tegner score between the two groups ( P>0.05). IKDC score, Lyshlom score, and Tegner score were used to evaluate the functional recovery of the affected knee before operation and at 3, 6, and 12 months after operation. CT scan and three-dimensional reconstruction were performed before and after operation to measure the horizontal distance from ADC to the anterior cartilage margin (L) and the horizontal distance from ADC to the center of the femoral canal (I), and the anteroposterior position of the bone canal (R) was calculated by I/L; the distance from the center to the distal cartilage margin (D) was measured on the two-dimensional cross section; the R value and D value were compared between the two groups.@*RESULTS@#The operation time of the study group was significantly less than that of the control group [ MD=-6.90 (-8.78, -5.03), P<0.001]. The incisions of the two groups healed by first intention, and no complication such as intra-articular infection, nerve injury, and deep vein thrombosis of lower limbs occurred. There was no significant difference in the R value and D value between the preoperative simulated positioning and the actual intraoperative positioning in the study group [ MD=0.52 (-2.85, 3.88), P=0.758; MD=0.36 (-0.39, 1.11), P=0.351]. There was no significant difference in the actual intraoperative positioning R value and D value between the study group and the control group [ MD=1.01 (-2.57, 4.58), P=0.573; MD=0.24 (-0.34, 0.82), P=0.411]. The patients in both groups were followed up 12-13 months (mean, 12.4 months). The IKDC score, Lysholm score, and Tegner score of the two groups increased gradually with time, and there were significant differences between pre- and post-operation ( P<0.05). There was no significant difference in the scores between the two groups at each time point after operation ( P>0.05).@*CONCLUSION@#The personalized femoral locator based on ADC can accurately assist the femoral tunnel positioning in ACL reconstruction, which can shorten the operation time when compared with traditional surgical methods, and achieve satisfactory early effectiveness.

Three-dimensional kinematic analysis of knee joint after anterior cruciate ligament reconstruction with personalized femoral positioner based on apex of deep cartilage / 中国修复重建外科杂志

OBJECTIVE@#To investigate the changes of knee joint kinematics after anterior cruciate ligament (ACL) reconstruction assisted by personalized femoral positioner based on the apex of deep cartilage (ADC).@*METHODS@#Between January 2021 and January 2022, a total of 40 patients with initial ACL rupture who met the selection criteria were randomly divided into the study group (using the personalized femoral positioner based on ADC design to assist ACL reconstruction) and the control group (not using the personalized femoral positioner to assist ACL reconstruction), with 20 patients in each group. Another 20 volunteers with normal knee were collected as a healthy group. There was no significant difference in gender, age, body mass index, and affected side between groups ( P>0.05). Gait analysis was performed at 3, 6, and 12 months after operation using Opti _ Knee three-dimensional knee joint motion measurement and analysis system, and the 6 degrees of freedom (flexion and extension angle, varus and valgus angle, internal and external rotation angle, anteroposterior displacement, superior and inferior displacement, internal and external displacement) and motion cycle (maximum step length, minimum step length, and step frequency) of the knee joint were recorded. The patients' data was compared to the data of healthy group.@*RESULTS@#In the healthy group, the flexion and extension angle was (57.80±3.45)°, the varus and valgus angle was (10.54±1.05)°, the internal and external rotation angle was (13.02±1.66)°, and the anteroposterior displacement was (1.44±0.39) cm, the superior and inferior displacement was (0.86±0.20) cm, and the internal and external displacement was (1.38±0.39) cm. The maximum step length was (51.24±1.29) cm, the minimum step length was (45.69±2.28) cm, and the step frequency was (12.45±0.47) step/minute. Compared with the healthy group, the flexion and extension angles and internal and external rotation angles of the patients in the study group and the control group decreased at 3 months after operation, and the flexion and extension angles of the patients in the control group decreased at 6 months after operation, and the differences were significant ( P<0.05); there was no significant difference in the other time points and other indicators when compared with healthy group ( P>0.05). In the study group, the flexion and extension angles and internal and external rotation angles at 6 and 12 months after operation were significantly greater than those at 3 months after operation ( P<0.05), while there was no significant difference in the other indicators at other time points ( P>0.05). There was a significant difference in flexion and extension angle between the study group and the control group at 6 months after operation ( P<0.05), but there was no significant difference of the indicators between the two groups at other time points ( P>0.05).@*CONCLUSION@#Compared with conventional surgery, ACL reconstruction assisted by personalized femoral positioner based on ADC design can help patients achieve more satisfactory early postoperative kinematic results, and three-dimensional kinematic analysis can more objectively and dynamically evaluate the postoperative recovery of knee joint.

Freeze-thaw-stable high internal phase emulsions stabilized by soy protein isolate and chitosan complexes at pH 3.0 as promising mayonnaise replacers.

The development of cholesterol-free mayonnaise has attracted increasing interest in the food colloid field, due to the potential health concerns as a result of consumption of cholesterol-rich mayonnaise. One effective strategy in this regard is to substitute or partially substitute egg yolk with other organic emulsifiers and stabilizers, without affecting the quality of the product. In the work, we reported an effective strategy to fabricate high freeze-thaw-stability high internal phase emulsions (HIPEs), using complexes of a heated soy protein isolate (SPI) and chitosan (CS) at pH 3.0 as the emulsifiers and stabilizers. The SPI/CS complexes, formed even at a very low CS-to-SPI ratio, e.g., 1:10, showed a high capacity to stabilize HIPEs with a high freeze-thaw stability. Increasing the CS-to-SPI ratio in the complexes resulted in a progressive strengthening of gel network in the corresponding HIPEs, together with a gradual improvement of emulsification performance. The gel network of the HIPEs stabilized by the SPI/CS complexes was mainly maintained by the inter-droplet noncovalent interactions involving the CS molecules. The presence of CS also progressively increased the percentage of adsorbed proteins at the interface, and decreased the surface coverage of proteins at the interface. The high freeze-thaw stability of such HIPEs might be unrelated to the ice crystal formation during the freezing, and was more likely associated with the strong steric repulsion contributed to the adsorbed CS molecules between different droplets. The results indicated that the complexation of heated SPI and CS could provide an effective strategy to facilely fabricate outstanding freeze-thaw-stability HI PEs as potential mayonnaise replacers.

Clinical characteristics of IgE-mediated cow's milk protein allergy in children / 中华儿科杂志

Objective: To analyze the clinical features of IgE-mediated cow's milk protein allergy (CMPA) in children aged 0-5 years. Methods: This cross-sectional study collected the data on children diagnosed with CMPA in the Department of Allergy at the Children's Hospital of the Capital Institute of Pediatrics from October 2019 to November 2020 and improved peripheral blood routine,total IgE defection, milk specific IgE (sIgE) defection,SPT and milk component defection,diagnosis of severe anaphylaxis based on clinical manifestations. Rank-sum test and chi-square test are used for statistical analysis of clinical characteristics between groups. Results: A total of 106 children (67 boys and 39 girls) were enrolled with the age of 15 (8, 34) months, including 42 cases (≤ 1 year of age), 39 cases (>1-<3 years of age) and 25 cases(≥3 years of age), the onset age of 6 (5, 8) months. Among them, 95 cases (89.6%) were reacted after consuming milk or its products, 42 cases (39.6%) had reaction due to skin contact and 11 cases (10.4%) reacted after exclusive breastfeeding. The onset time of milk product consumption was 45 (1, 120) min, skin contact pathway was 10 (5, 30) min and symptoms in breastfeeding pathway was 121 (61, 180) min. There was statistical difference among the time of symptoms (χ2=77.01, P<0.001).The cutaneous reaction was most common (100 cases, 94.3%), followed by digestive (20 cases, 18.9%) and respiratory (16 cases, 15.1%), and the nervous symptoms (1 case, 0.9%) were uncommon and 24 cases (22.6%) had at least one episode of anaphylaxis. There were 87 cases (82.1%) also diagnosed with other food allergies, 94 cases (88.7%) with previous eczema, 57 cases (53.8%) with history of rhinitis, and 23 cases (21.7%) with history of wheezing. The total IgE level was 191.01 (64.71, 506.80) kU/L, and the cow's milk sIgE level was 3.03 (1.11, 15.24) kU/L. The maximum diameter of the wheal in SPT was 8.2 (4.0, 12.0) mm. Component resolved diagnosis showed that 77 cases (81.9%) were sensitized to at least one out of 4 main components, including casein, α lactalbumin, β lactoglobulin and bovine serum albumin.The possibility of anaphylaxis in children with milk sIgE grade Ⅳ-Ⅵ was higher than that in children with grade 0-Ⅲ (57.7% (15/26) vs. 12.5% (10/80), OR=9.545, 95%CI 3.435-26.523). Children with milk SPT ≥+++ had a higher probability of anaphylaxis than those with milk SPT ≤++ (34.4% (11/32) vs. 11.5% (3/26), OR=4.016, 95%CI 0.983-16.400). Anaphylaxis were more common in α lactalbumin positive children than in negative children (34.3% (13/38) vs. 14.2% (8/56), χ2=1.23，P=0.042). Conclusions: CMPA in children has early onset and diversified clinical manifestations, which are mainly cutaneous symptoms. Most children are sensitized to at least one allergen component. Serum sIgE level, SPT reaction and allergen components play important roles in the diagnosis and evaluation of CMPA, and higher milk sIgE level may predict a higher risk of anaphylaxis.

Risk prediction model of in-hospital mortality in heart failure with preserved ejection fraction and mid-range ejection fraction: a retrospective cohort study.

Aim: To develop and validate internally a multivariate risk model for predicting the in-hospital mortality of patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mid-range ejection fraction (HFmrEF). Methods & results: The clinical data of 8172 inpatients with HFpEF and HFmrEF was used to establish a retrospective database. These patients, among whom 307 in-hospital deaths (3.8%) occurred, were randomly assigned to derivation and verification cohort. Among the extracted data from the derivation cohort were nine variables significantly related to in-hospital mortality, which were scored 0-4, for a total score of 24, which allowed formation of a risk predictive model. The verification cohort was then used to validate the discrimination and calibration capacities of this predictive model: the area under curve equaled 0.8575 (0.8285, 0.8865) for the derivation cohort, and 0.8323 (0.7999, 0.8646) for the verification cohort. According to this risk score, we divided patients into four risk classes (low-, medium-, high- and extremely high-risk) and revealed that the risk of in-hospital mortality increased with increasing risk class with an obvious linear relationship between actual and predicted mortality (r = 0.998, p < 0.001). Conclusion: The model based on nine common clinical variables should provide an accurate prediction of in-hospital mortality and appears to be a reliable risk classification system for patients with HFpEF and HFmrEF.

Efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children: a real-world study. / æ§æžé»„é¢—ç²’è¾ åŠ©æ²»ç–—å„¿ç«¥æ”¯æ°”ç®¡å“®å–˜ç–—æ•ˆçš„çœŸå®žä¸–ç•Œç ”ç©¶.

OBJECTIVES: To study the efficacy of Huaiqihuang granules as adjuvant therapy for bronchial asthma in children. METHODS: A multicenter, prospective, and registered real-world study was performed for the children, aged 2-5 years, who had a confirmed diagnosis of bronchial asthma in the outpatient service of 21 hospitals in China. Among these children, the children treated with medications for long-term asthma control (inhaled corticosteroid and/or leukotriene receptor antagonist) without Huaiqihuang granules were enrolled as the control treatment group, and those treated with medications for long-term asthma control combined with Huaiqihuang granules were enrolled as the combined treatment group. The medical data of all children were collected. Outpatient or telephone follow-up was performed at weeks 4, 8, 12, 20, 28, and 36 after treatment, including asthma attacks and rhinitis symptoms. A statistical analysis was performed for the changes in these indices. RESULTS: There was no significant difference in the frequency of asthma attacks or rhinitis attacks between the two groups before treatment (P>0.05). After treatment, the combined treatment group had significantly lower frequencies of asthma attacks, severe asthma attacks, and rhinitis attacks compared with the control treatment group (P<0.05). There was no signification difference in the incidence rate of adverse reactions between the two groups (P=0.667). CONCLUSIONS: Huaiqihuang granules in addition to medications for long-term asthma control can alleviate the symptoms of bronchial asthma and rhinitis and improve the level of asthma control in children with bronchial asthma, with good safety and little adverse effect. Citation.

Heteroprotein Complex Coacervate Based on ß-Conglycinin and Lysozyme: Dynamic Protein Exchange, Thermodynamic Mechanism, and Lysozyme Activity.

Heteroprotein complex coacervate (HPCC) is a liquid-like protein concentrate produced by liquid-liquid phase separation. We revealed the protein dynamic exchange and thermodynamic mechanism of ß-conglycinin/lysozyme coacervate, and clarified the effect of HPCC on protein structure and activity. ß-conglycinin and lysozyme assembled into coacervate at pH 5.75-6.5 and assembled into amorphous precipitates at higher pH. As the pH dropped from 8 to 6, the number of binding sites of the complex decreased in half, and the desolvation degree corresponding to the entropy gain was greatly reduced, conducing to the formation of coacervates rather than precipitates. The coacervates achieved the unique dynamic exchange by exchanging proteins with the diluted phase, making the uniform distribution of proteins in coacervates. The lysozyme activity was completely retained in ß-conglycinin/lysozyme coacervates. These results proved that ß-conglycinin-based heteroprotein complex coacervate is a feasible method to encapsulate and enrich active proteins in a purely aqueous environment.

Assembled milk protein nano-architectures as potential nanovehicles for nutraceuticals.

Nanoencapsulation of hydrophobic nutraceuticals with food ingredients has become one of topical research subjects in food science and pharmaceutical fields. To fabricate food protein-based nano-architectures as nanovehicles is one of effective strategies or approaches to improve water solubility, stability, bioavailability and bioactivities of poorly soluble or hydrophobic nutraceuticals. Milk proteins or their components exhibit a great potential to assemble or co-assemble with other components into a variety of nano-architectures (e.g., nano-micelles, nanocomplexes, nanogels, or nanoparticles) as potential nanovehicles for encapsulation and delivery of nutraceuticals. This article provides a comprehensive review about the state-of-art knowledge in utilizing milk proteins to assemble or co-assemble into a variety of nano-architectures as promising encapsulation and delivery nano-systems for hydrophobic nutraceuticals. First, a brief summary about composition, structure and physicochemical properties of milk proteins, especially caseins (or casein micelles) and whey proteins, is presented. Then, the disassembly and reassembly behavior of caseins or whey proteins into nano-architectures is critically reviewed. For caseins, casein micelles can be dissociated and further re-associated into novel micelles, through pH- or high hydrostatic pressure-mediated disassembly and reassembly strategy, or can be directly formed from caseinates through a reassembly process. In contrast, the assembly of whey protein into nano-architectures usually needs a structural unfolding and subsequent aggregation process, which can be induced by heating, enzymatic hydrolysis, high hydrostatic pressure and ethanol treatments. Third, the co-assembly of milk proteins with other components into nano-architectures is also summarized. Last, the potential and effectiveness of assembled milk protein nano-architectures, including reassembled casein micelles, thermally induced whey protein nano-aggregates, α-lactalbumin nanotubes or nanospheres, co-assembled milk protein-polysaccharide nanocomplexes or nanoparticles, as nanovehicles for nutraceuticals (especially those hydrophobic) are comprehensively reviewed. Due to the fact that milk proteins are an important part of diets for human nutrition and health, the review is of crucial importance not only for the development of novel milk protein-based functional foods enriched with hydrophobic nutraceuticals, but also for providing the newest knowledge in the utilization of food protein assembly behavior in the nanoencapsulation of nutraceuticals.

Nano-architectural assembly of soy proteins: A promising strategy to fabricate nutraceutical nanovehicles.

Use of protein-based nanovehicles has been well recognized to be one of the most effective strategies to improve water dispersibility, stability and bioavailability of nutraceuticals or bioactive ingredients. Thanks to their health-benefiting effects and unique assembly behavior, soy proteins seem to be the perfect food proteins for fabricating nanovehicles in this regard. This review presents the state-of-art knowledge about the assembly of soy proteins into nano-architectures, e. g., nanoparticles, nanocomplexes or nanogels, induced by different physicochemical strategies and approaches. The strategies to trigger the assembly of soy proteins into a variety of nano-architectures are highlighted and critically reviewed. Such strategies include heating, enzymatic hydrolysis, pH shift, urea or ethanol treatment, reduction, and static high pressure treatment. The self-assembly behavior of soy proteins (native or denatured) is also reviewed. Besides the assembly of proteins alone, soy proteins can co-assemble with polysaccharides to form versatile nano-architectures, through different processes, e.g., heating or ultrasonication. Finally, recent progress in the development of assembled soy protein nano-architectures as nanovehicles for hydrophobic nutraceuticals is briefly summarized. With the fast increasing health awareness for natural and safe functional foods, this review is of crucial relevance for providing an important strategy to develop a kind of novel soy protein-based functional foods with dual-function health effects from soy proteins and nutraceuticals.

Low-Dose Decitabine Monotherapy Reverses Mixed Chimerism in Adult Patients After Allogeneic Hematopoietic Stem Cell Transplantation With Myeloablative Conditioning Regimen: A Pilot Phase II Study.

T cell mixed chimerism (MC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) with myeloablative conditioning for hematological malignancies may indicate engraftment failure or disease relapse. Immune modulation, such as donor lymphocyte infusion (DLI) or the rapid tapering-off or stopping of immunosuppressive treatment, can reverse MC to full donor chimerism (FDC). However, the development or aggravation of graft-versus-host disease (GvHD) and the related mortality remain major concerns with immune modulation. In this prospective, single-arm study (NCT03663751), we tested the efficacy and safety of low-dose decitabine (LD-DAC, 5 mg/m2 daily for 5 days and repeated every 6-8 weeks) without immune modulation in the treatment of patients with MC to prevent MC-associated relapse and/or graft failure. A total of 14 patients were enrolled. All the patients received myeloablative conditioning regimens, and MC was documented from day +30 to day +180 after allo-HSCT with a donor chimerism level ranging from 59 to 97% without detectable measurable residual disease (MRD). Eleven patients (78.6%) responded favorably to treatment, showing increased levels of donor chimerism (≥95%), while nine achieved FDC. All of these patients maintained their responses for a median of 11 months (3-22). The three patients who failed to respond favorably eventually either relapsed or experienced graft failure. All three were alive and in remission at the last follow-up after the second allo-HSCT. LD-DAC monotherapy was well tolerated and exerted limited hematological and nonhematological toxicities. New-onset GvHD symptoms were observed only in two patients. Overall, the estimated 2-year overall survival (OS) and event-free survival (EFS) after allo-HSCT were 90.9 ± 8.7% and 67.0 ± 13.7%, respectively. In conclusion, LD-DAC alone could reverse MC in most patients after allo-HSCT with myeloablative conditioning, while those who achieved FDC enjoyed long-term EFS without major complications. Further prospective studies with larger sample sizes are warranted to confirm the benefits of LD-DAC.

Brahma-Related Gene-1 (BRG1) promotes the malignant phenotype of glioblastoma cells.

Glioblastoma multiforme (GBM) is an aggressive malignant brain tumour that is resistant to existing therapeutics. Identifying signalling pathways deregulated in GBM that can be targeted therapeutically is critical to improve the present dismal prognosis for GBM patients. In this report, we have identified that the BRG1 (Brahma-Related Gene-1) catalytic subunit of the SWI/SNF chromatin remodelling complex promotes the malignant phenotype of GBM cells. We found that BRG1 is ubiquitously expressed in tumour tissue from GBM patients, and high BRG1 expression levels are localized to specific brain tumour regions. Knockout (KO) of BRG1 by CRISPR-Cas9 gene editing had minimal effects on GBM cell proliferation, but significantly inhibited GBM cell migration and invasion. BRG1-KO also sensitized GBM cells to the anti-proliferative effects of the anti-cancer agent temozolomide (TMZ), which is used to treat GBM patients in the clinic, and selectively altered STAT3 tyrosine phosphorylation and gene expression. These results demonstrate that BRG-1 promotes invasion and migration, and decreases chemotherapy sensitivity, indicating that it functions in an oncogenic manner in GBM cells. Taken together, our findings suggest that targeting BRG1 in GBM may have therapeutic benefit in the treatment of this deadly form of brain cancer.

Analysis of factors responsible for residual rectal neuroendocrine tumor at the margins following endoscopic resection in middle-aged and elderly patients / 中华老年医学杂志

Objective:To examine the factors related to residual rectal neuroendocrine tumor at the margins after endoscopic resection.Methods:A retrospective case control study was conducted.From January 1, 2013 to March 31, 2018, data on 81 middle-aged and elderly patients with rectal neuroendocrine tumor aged ≥45 years who underwent endoscopic resection at the Endoscopic Center of the First Hospital of Jilin University were retrospectively collected.Based on whether residual tumor existed on histopathological examination, they were divided into the residual group(n=22)and the non-residual group(n=59). The causes of residual rectal neuroendocrine tumor at the margins after endoscopic resection were analyzed.Results:The diameters of lesions in 81 patients with rectal neuroendocrine tumors ranged between 0.3-1.5(0.73±0.33)cm.Postoperative histopathological examination revealed that all lesions were G1 neuroendocrine tumors, with residual tumor seen at the margins in 22 cases(27.2%). The mean tumor diameter was(0.78±0.36)cm for the residual group and(0.68±0.28)cm for the non-residual group, with no statistical significance between the two groups( t=1.320, P>0.05). Of the 22 patients in the residual group, 2 cases showed muscularis propria involvement and 14 cases showed tumor infiltration into the submucosa but without lymph node infiltration or metastasis, and in the rest of the cases lesions were confined to the mucosa.None of the 59 patients in the non-residual group had involvement of the muscular layer, but 23 cases showed tumor infiltration into the submucosa(39.0%)and the rest had lesions confined to the mucosa.The difference between the two groups was statistically significant( χ2=11.010, P<0.01). The results of binary Logistic regression analysis suggested that tumor infiltration into or beyond the submucosa( β=1.285, P<0.05)and the absence of preoperative ultrasonographic evaluation( β=-1.147, P<0.05)were independent risk factors for residual rectal neuroendocrine tumor at the margins after endoscopic resection. Conclusions:Tumor infiltration into the submucosa or beyond and lack of preoperative ultrasound evaluation are independent risk factors for residual rectal neuroendocrine tumor at the margins after endoscopic resection.